• The Interactive Fly

    Mechanisms of Evolution


    Extensive local adaptation within the chemosensory system following Drosophila melanogaster's global expansion

    How organisms adapt to new environments is of fundamental biological interest, but poorly understood at the genetic level. Chemosensory systems provide attractive models to address this problem, because they lie between external environmental signals and internal physiological responses. To investigate how selection has shaped the well-characterized chemosensory system of Drosophila melanogaster, this study analysed genome-wide data from five diverse populations. By couching population genomic analyses of chemosensory protein families, including odorant receptors, gustatory receptors, and odorant-binding proteins, within parallel analyses of other large families, it was demonstrated that chemosensory proteins are not outliers for adaptive divergence between species. However, chemosensory families often display the strongest genome-wide signals of recent selection within D. melanogaster. Recent adaptation has operated almost exclusively on standing variation, and patterns of adaptive mutations predict diverse effects on protein function. Finally, evidence is provided that chemosensory proteins have experienced relaxed constraint, and it is argued that this has been important for their rapid adaptation over short timescales (Arguello, 2016).

    A 24 h age difference causes twice as much gene expression divergence as 100 generations of adaptation to a novel environment

    Gene expression profiling is one of the most reliable high-throughput phenotyping methods, allowing researchers to quantify the transcript abundance of expressed genes. Because many biotic and abiotic factors influence gene expression, it is recommended to control them as tightly as possible. This study shows that a 24 h age difference of Drosophila simulans females that were subjected to RNA sequencing (RNA-Seq) five and six days after eclosure resulted in more than 2000 differentially expressed genes. This is twice the number of genes that changed expression during 100 generations of evolution in a novel hot laboratory environment. Importantly, most of the genes differing in expression due to age introduce false positives or negatives if an adaptive gene expression analysis is not controlled for age. These results indicate that tightly controlled experimental conditions, including precise developmental staging, are needed for reliable gene expression analyses, in particular in an evolutionary framework (Hsu, 2019).

    Inverse resource allocation between vision and olfaction across the genus Drosophila

    Divergent populations across different environments are exposed to critical sensory information related to locating a host or mate, as well as avoiding predators and pathogens. These sensory signals generate evolutionary changes in neuroanatomy and behavior; however, few studies have investigated patterns of neural architecture that occur between sensory systems, or that occur within large groups of closely-related organisms. This study examine 62 species within the genus Drosophila and describes an inverse resource allocation between vision and olfaction, which was consistently observe at the periphery, within the brain, as well as during larval development. This sensory variation was noted across the entire genus and appears to represent repeated, independent evolutionary events, where one sensory modality is consistently selected for at the expense of the other. Moreover, evidence is provided of a developmental genetic constraint through the sharing of a single larval structure, the eye-antennal imaginal disc. In addition, the ecological implications of visual or olfactory bias were examined, including the potential impact on host-navigation and courtship (Keesey, 2019).

    Local thermal adaptation detected during multiple life stages across populations of Drosophila melanogaster

    Thermal adaptation is typically detected by examining the tolerance of a few populations to extreme temperatures within a single life stage. However, the extent to which adaptation occurs among many different populations might depend on the tolerance of multiple life stages and the average temperature range that the population experiences. This study examined local adaptation to native temperature conditions in eleven populations of the well-known cosmopolitan fruit fly, Drosophila melanogaster. These populations were sampled from across the global range of D. melanogaster. Traits related to fitness were measured during each life stage to determine if certain stages are more sensitive to changes in temperature than others. D. melanogaster appeared to show local adaptation to native temperatures during the egg, larval, and adult life stages, but not the pupal stage. This suggests that across the entire distribution of D. melanogaster, certain life stages might be locally adapted to native temperatures, while other stages might use phenotypic plasticity or tolerance to a wide range of temperatures experienced in the native environment of this species (Austin, 2019).

    Interspecies comparative analyses reveal distinct carbohydrate-responsive systems among Drosophila species

    During evolution, organisms have acquired variable feeding habits. Some species are nutritional generalists that adapt to various food resources, while others are specialists, feeding on specific resources. However, much remains to be discovered about how generalists adapt to diversified diets. Larvae of the generalists Drosophila melanogaster and D. simulans develop on three diets with different nutrient balances, whereas specialists D. sechellia and D. elegans cannot develop on carbohydrate-rich diets. The generalist D. melanogaster downregulates the expression of diverse metabolic genes systemically by transforming growth factor beta (TGF-beta)/Activin signaling, maintains metabolic homeostasis, and successfully adapts to the diets. In contrast, the specialist D. sechellia expresses those metabolic genes at higher levels and accumulates various metabolites on the carbohydrate-rich diet, culminating in reduced adaptation. Phenotypic similarities and differences strongly suggest that the robust carbohydrate-responsive regulatory systems are evolutionarily retained through genome-environment interactions in the generalists and contribute to their nutritional adaptabilities (Watanabe, 2019).

    Major range loss predicted from lack of heat adaptability in an alpine Drosophila species

    Climate warming is threatening biodiversity worldwide. Climate specialists such as alpine species are especially likely to be vulnerable. Adaptation by rapid evolution is the only long-term option for survival of many species, but the adaptive evolutionary potential of heat resistance has not been assessed in an alpine invertebrate. This study show that the alpine fly Drosophila nigrosparsa cannot readily adapt to heat stress. Heat-exposed flies from a regime with increased ambient temperature and a regime with increased temperature plus artificial selection for heat tolerance were less heat tolerant than the control group. Increased ambient temperature affected negatively both fitness and competitiveness. Ecological niche models predicted the loss of three quarters of the climatically habitable areas of this fly by the end of this century. These findings suggest that, alongside with other climate specialists, species from mountainous regions are highly vulnerable to climate warming and unlikely to adapt through evolutionary genetic changes (Kinzner, 2019).

    Genomic analysis of the four ecologically distinct cactus host populations of Drosophila mojavensis

    Relationships between an organism and its environment can be fundamental in the understanding how populations change over time and species arise. Local ecological conditions can shape variation at multiple levels, among these are the evolutionary history and trajectories of coding genes. This study examines the rate of molecular evolution at protein-coding genes throughout the genome in response to host adaptation in the cactophilic Drosophila mojavensis. These insects are intimately associated with cactus necroses, developing as larvae and feeding as adults in these necrotic tissues. Drosophila mojavensis is composed of four isolated populations across the deserts of western North America and each population has adapted to utilize different cacti that are chemically, nutritionally, and structurally distinct. High coverage Illumina sequencing was performed on three previously unsequenced populations of D. mojavensis. Genomes were assembled using the previously sequenced genome of D. mojavensis from Santa Catalina Island (USA) as a template. Protein coding genes were aligned across all four populations and rates of protein evolution were determined for all loci using a several approaches. Loci that exhibited elevated rates of molecular evolution tend to be shorter, have fewer exons, low expression, be transcriptionally responsive to cactus host use and have fixed expression differences across the four cactus host populations. Fast evolving genes were involved with metabolism, detoxification, chemosensory reception, reproduction and behavior. Results of this study give insight into the process and the genomic consequences of local ecological adaptation (Allan, 2019).

    Microbiome composition shapes rapid genomic adaptation of Drosophila melanogaster

    Population genomic data has revealed patterns of genetic variation associated with adaptation in many taxa. Yet understanding the adaptive process that drives such patterns is challenging; it requires disentangling the ecological agents of selection, determining the relevant timescales over which evolution occurs, and elucidating the genetic architecture of adaptation. Doing so for the adaptation of hosts to their microbiome is of particular interest with growing recognition of the importance and complexity of host-microbe interactions. This study tracked the pace and genomic architecture of adaptation to an experimental microbiome manipulation in replicate populations of Drosophila melanogaster in field mesocosms. Shifts in microbiome composition altered population dynamics and led to divergence between treatments in allele frequencies, with regions showing strong divergence found on all chromosomes. Moreover, at divergent loci previously associated with adaptation across natural populations, the more common allele was found in fly populations experimentally enriched for a certain microbial group was also more common in natural populations with high relative abundance of that microbial group. These results suggest that microbiomes may be an agent of selection that shapes the pattern and process of adaptation and, more broadly, that variation in a single ecological factor within a complex environment can drive rapid, polygenic adaptation over short timescales (Rudman, 2019).

    Decreased temperature sensitivity of Vestigial gene expression in temperate populations of Drosophila melanogaster

    Drosophila melanogaster recently spread from its tropical origin in Africa and became a cosmopolitan species that has adapted to a wide range of different thermal environments, including temperate climates. An important limiting factor of temperate climates has probably been their low and varying temperatures. The transcriptional output of genes can vary across temperatures, which might have been detrimental while settling in temperate environments. The reduction of temperature-sensitive expression of functionally important genes to ensure consistent levels of gene expression might have been relevant while adapting to such environments. This study focuses on the gene vestigial (vg) whose product is a key factor in wing development. Evidence is provided that temperature-sensitivity of vg has been buffered in populations from temperate climates. Temperature-sensitivity of vg gene expression was investigated in six natural populations, including four temperate populations (three from Europe and one from high-altitude Africa), and two tropical populations from the ancestral species range. All temperate populations exhibited a lower degree of temperature-induced expression plasticity than the tropical populations (Voigt, 2019).

    Recurrent collection of Drosophila melanogaster from Wild african environments and genomic insights into species history

    Drosophila melanogaster is thought to originate from sub-Saharan Africa. This study documents the collection of 288 D. melanogaster individuals from multiple African wilderness areas in Zambia, Zimbabwe, and Namibia. The presence of D. melanogaster in these remote woodland environments is consistent with an ancestral range in southern-central Africa, as opposed to equatorial regions. After sequencing the genomes of 17 wilderness-collected flies collected from Kafue National Park in Zambia, reduced genetic diversity relative to town populations, elevated chromosomal inversion frequencies, and strong differences at specific genes including known insecticide targets were found. Combining these genomes with existing data, this study probed the history of this species' geographic expansion. Demographic estimates indicated that expansion from southern-central Africa began approximately 10,000 years ago, with a Saharan crossing soon after, but expansion from the Middle East into Europe did not begin until roughly 1,400 years ago. This improved model of demographic history will provide an important resource for future evolutionary and genomic studies of this key model organism. These findings add context to the history of D. melanogaster, while opening the door for future studies on the biological basis of adaptation to human environments (Sprengelmeyer, 2019).

    A-to-I RNA editing uncovers hidden signals of adaptive genome evolution in animals

    In animals, the most common type of RNA editing is the deamination of adenosines (A) into inosines (I). Because inosines base-pair with cytosines (C), they are interpreted as guanosines (G) by the cellular machinery and genomically encoded G alleles at edited sites mimic the function of edited RNAs. The contribution of this hardwiring effect on genome evolution remains obscure. This study looked for population genomics signatures of adaptive evolution associated with A-to-I RNA edited sites in humans and Drosophila melanogaster. Single nucleotide polymorphisms at edited sites occur 3 (humans) to 15 times (Drosophila) more often than at unedited sites, the nucleotide G is virtually the unique alternative allele at edited sites and G alleles segregate at higher frequency at edited sites than at unedited sites. This study study reveals that a significant fraction of coding synonymous and nonsynonymous as well as silent and intergenic A-to-I RNA editing sites are likely adaptive in the distantly related human and Drosophila lineages (Popitsch, 2020).

    Rapid sex-specific adaptation to high temperature in Drosophila

    The pervasive occurrence of sexual dimorphism demonstrates different adaptive strategies of males and females. While different reproductive strategies of the two sexes are well-characterized, very little is known about differential functional requirements of males and females in their natural habitats. The impact environmental change on the selection response was studied in both sexes. Exposing replicated Drosophila populations to a novel temperature regime, sex-specific changes were demonstrated in gene expression, metabolic and behavioral phenotypes in less than 100 generations. This indicates not only different functional requirements of both sexes in the new environment but also rapid sex-specific adaptation. Supported by computer simulations it is proposed that altered sex-biased gene regulation from standing genetic variation, rather than new mutations, is the driver of rapid sex-specific adaptation. This discovery of environmentally driven divergent functional requirements of males and females has important implications-possibly even for gender aware medical treatments (Hsu, 2020).

    Evolution of cross-tolerance in Drosophila melanogaster as a result of increased resistance to cold stress

    Cold stress is a critical environmental challenge that affects an organism's fitness-related traits. In Drosophila, increased resistance to specific environmental stress may lead to increased resistance to other kinds of stress. This study aimed to understand whether increased cold stress resistance in Drosophila melanogaster can facilitate their ability to tolerate other environmental stresses. This study used successfully selected replicate populations of D. melanogaster against cold shock and their control population. The present work investigated egg viability and mating frequency with and without heat and cold shock conditions in the selected and their control populations. Resistance to cold shock, heat shock, desiccation, starvation, and survival post-challenge with Staphylococcus succinus subsp. succinus PK-1 were also examined in the selected and their control populations. After cold-shock treatment, it was found a 1.25 times increase in egg viability and a 1.57 times increase in mating frequency in the selected populations compared to control populations. Moreover, more males (0.87 times) and females (1.66 times) of the selected populations survived under cold shock conditions relative to their controls. After being subjected to heat shock, the selected population's egg viability and mating frequency increased by 0.30 times and 0.57 times, respectively, compared to control populations. Additionally, more selected males (0.31 times) and females (0.98 times) survived under heat shock conditions compared to the control populations. Desiccation resistance slightly increased in the females of the selected populations relative to their control, but no change was observed in the case of males. Starvation resistance decreased in males and females of the selected populations compared to their controls. These findings suggest that the increased resistance to cold shock correlates with increased tolerance to heat stress, but this evolved resistance comes at a cost, with decreased tolerance to starvation (Singh, 2022).

    Temperature driven gene expression evolution in natural and laboratory populations highlights the crucial role of correlated fitness effects for polygenic adaptation

    The influence of pleiotropy on adaptive responses is a highly controversial topic, with limited empirical evidence available. Recognizing the pivotal role of the correlation of fitness effects, an experiment was designed to compare the adaptive gene expression evolution of natural and experimental populations. To test this, we studied the evolution of gene expression in response to temperature in two Drosophila species on a natural temperature cline in North America and replicated populations evolving in hot and cold temperature regimes. If fitness effects of affected traits are independent, pleiotropy is expected to constrain the adaptive response in both settings. However, when fitness effects are more correlated in natural populations, adaptation in the wild will be facilitated by pleiotropy. Remarkably, evidence was found for both predicted effects. In both settings, genes with strong pleiotropic effects contribute less to adaptation, indicating that the majority of fitness effects are not correlated. In addition, this study also discovered that genes involved in adaptation exhibited more pleiotropic effects in natural populations. It is proposed that this pattern can be explained by a stronger correlation of fitness effects in nature. More insights into the dual role of pleiotropy will be crucial for the understanding of polygenic adaptation (Thorholludottir, 2023).

    The Transmission Patterns of the Endosymbiont Wolbachia within the Hawaiian Drosophilidae Adaptive Radiation

    The evolution of endosymbionts and their hosts can lead to highly dynamic interactions with varying fitness effects for both the endosymbiont and host species. Wolbachia, a ubiquitous endosymbiont of arthropods and nematodes, can have both beneficial and detrimental effects on host fitness. This study documented the occurrence and patterns of transmission of Wolbachia within the Hawaiian Drosophilidae and examined the potential contributions of Wolbachia to the rapid diversification of their hosts. Screens for Wolbachia infections across a minimum of 140 species of Hawaiian Drosophila and Scaptomyza revealed species-level infections of 20.0%, and across all 399 samples, a general infection rate of 10.3%. Among the 44 Wolbachia strains identified using a modified Wolbachia multi-locus strain typing scheme, 30 (68.18%) belonged to supergroup B, five (11.36%) belonged to supergroup A, and nine (20.45%) had alleles with conflicting supergroup assignments. Co-phylogenetic reconciliation analysis indicated that Wolbachia strain diversity within their endemic Hawaiian Drosophilidae hosts can be explained by vertical (e.g., co-speciation) and horizontal (e.g., host switch) modes of transmission. Results from stochastic character trait mapping suggest that horizontal transmission is associated with the preferred oviposition substrate of the host, but not the host's plant family or island of occurrence. For Hawaiian Drosophilid species of conservation concern, with 13 species listed as endangered and one listed as threatened, knowledge of Wolbachia strain types, infection status, and potential for superinfection could assist with conservation breeding programs designed to bolster population sizes, especially when wild populations are supplemented with laboratory-reared, translocated individuals. Future research aimed at improving the understanding of the mechanisms of Wolbachia transmission in nature, their impact on the host, and their role in host species formation may shed light on the influence of Wolbachia as an evolutionary driver, especially in Hawaiian ecosystems (Corpuz, 2023).

    Neuronal function and dopamine signaling evolve at high temperature in Drosophila

    Neuronal activity is temperature-sensitive and affects behavioral traits important for individual fitness, such as locomotion and courtship. Yet not enough is known about the evolutionary response of neuronal phenotypes in new temperature environments. This study used long-term experimental evolution of Drosophila simulans populations exposed to novel temperature regimes. A direct relationship was demonstrated between thermal selective pressure and the evolution of neuronally expressed molecular and behavioral phenotypes. Several essential neuronal genes evolve lower expression at high temperatures and higher expression at low temperatures, with dopaminergic neurons standing out by displaying the most consistent expression change across independent replicates. The link between evolved gene expression and behavioral changes was functionally validated by pharmacological intervention in the experimentally evolved D. simulans populations as well as by genetically triggered expression changes of key genes in D. melanogaster. Since natural temperature clines confirm these results for Drosophila and Anopheles populations, it is concluded that neuronal dopamine evolution is a key factor for temperature adaptation (Jaksic, 2020).

    Genome-wide variation and transcriptional changes in diverse developmental processes underlie the rapid evolution of seasonal adaptation

    Many organisms enter a dormant state in their life cycle to deal with predictable changes in environments over the course of a year. The timing of dormancy is therefore a key seasonal adaptation, and it evolves rapidly with changing environments. The hypothesis that differences in the timing of seasonal activity are driven by differences in the rate of development during diapause was tested in Rhagoletis pomonella, a fly specialized to feed on fruits of seasonally limited host plants. Transcriptomes from the central nervous system across a time series during diapause show consistent and progressive changes in transcripts participating in diverse developmental processes, despite a lack of gross morphological change. Moreover, population genomic analyses suggested that many genes of small effect enriched in developmental functional categories underlie variation in dormancy timing and overlap with gene sets associated with development rate in Drosophila melanogaster. These transcriptional data also suggested that a recent evolutionary shift from a seasonally late to a seasonally early host plant drove more rapid development during diapause in the early fly population. Moreover, genetic variants that diverged during the evolutionary shift were also enriched in putative cis regulatory regions of genes differentially expressed during diapause development. Overall, these data suggest polygenic variation in the rate of developmental progression during diapause contributes to the evolution of seasonality in R. pomonella. Patterns that suggest hourglass-like developmental divergence early and late in diapause development are discussed along with an important role for hub genes in the evolution of transcriptional divergence (Dowle, 2020).

    Phenotypic coupling of sleep and starvation resistance evolves in D. melanogaster

    One hypothesis for the function of sleep is that it serves as a mechanism to conserve energy. Recent studies have suggested that increased sleep can be an adaptive mechanism to improve survival under food deprivation in Drosophila melanogaster. To test the generality of this hypothesis, Sleep and its plastic response to starvation was compared in a temperate and tropical population of Drosophila melanogaster. Flies from the temperate population were found to be more starvation resistant, and it was hypothesized that they would engage in behaviors that are considered to conserve energy, including increased sleep and reduced movement. Surprisingly, temperate flies slept less and moved more when they were awake compared to tropical flies, both under fed and starved conditions, therefore sleep did not correlate with population-level differences in starvation resistance. In contrast, total sleep and percent change in sleep when starved were strongly positively correlated with starvation resistance within the tropical population, but not within the temperate population. Thus, unexpectedly complex relationships between starvation and sleep were observed that vary both within and across populations. These observations falsify the simple hypothesis of a straightforward relationship between sleep and energy conservation. The hypothesis that starvation is correlated with metabolic phenotypes was tested by investigating stored lipid and carbohydrate levels; stored metabolites were found to partially contributed towards variation starvation resistance. These findings demonstrate that the function of sleep under starvation can rapidly evolve on short timescales and raise new questions about the physiological correlates of sleep and the extent to which variation in sleep is shaped by natural selection (Sarikaya, 2020).

    Adaptation of circadian neuronal network to photoperiod in high-latitude European Drosophilids
    The genus Drosophila contains over 2,000 species that, stemming from a common ancestor in the Old World Tropics, populate today very different environments. This study found significant differences in the activity pattern of Drosophila species belonging to the holarctic virilis group, i.e., D. ezoana and D. littoralis, collected in Northern Europe, compared to that of the cosmopolitan D. melanogaster, collected close to the equator. These behavioral differences might have been of adaptive significance for colonizing high-latitude habitats and hence adjust to long photoperiods. Most interestingly, the flies' locomotor activity correlates with the neurochemistry of their circadian clock network, which differs between low and high latitude for the expression pattern of the blue light photopigment cryptochrome (CRY) and the neuropeptide Pigment-dispersing factor (PDF). In D. melanogaster, CRY and PDF are known to modulate the timing of activity and to maintain robust rhythmicity under constant conditions. The rhythmic behavior of the high-latitude virilis group species could be partially stimulated by mimicking their CRY/PDF expression patterns in a laboratory strain of D. melanogaster. Data suggest that these alterations in the CRY/PDF clock neurochemistry might have allowed the virilis group species to colonize high-latitude environments (Menegazzi, 2017).

    Parallel gene expression evolution in natural and laboratory evolved populations

    Ecological adaptation is frequently inferred by the comparison of natural populations from different environments. Nevertheless, the inference of the selective forces suffers the challenge that many environmental factors covary. With well-controlled environmental conditions, experimental evolution provides a powerful approach to complement the analysis of natural populations. On the other hand, it is apparent that laboratory conditions differ in many ways from natural environments, which raises the question to what extent selection responses in experimental evolution studies can inform about adaptation processes in the wild. This study compared the expression profiles of replicated Drosophila melanogaster populations which have been exposed to two distinct temperature regimes (18/28 °C and 10/20 °C) in the laboratory for more than 80 generations. Using gene-wise differential expression analysis and co-expression network analysis, 541 genes and three co-regulated gene modules were identified that evolved in the same direction in both temperature regimes, and most of these changes probably reflect an adaptation to the space constrain or diurnal temperature fluctuation that is common in both selection regimes. 203 genes and seven modules evolved temperature-specific expression changes. Remarkably, a significant overlap was detected of these temperature-adaptive genes/modules from experimental evolution with temperature-adaptive genes inferred from natural Drosophila populations covering two different temperature clines. It is concluded that well-designed experimental evolution studies are a powerful tool to dissect evolutionary responses (Hsu, 2020).

    The evolution of phenotypic plasticity in response to temperature stress

    Phenotypic plasticity is the ability of a single genotype to produce different phenotypes in response to environmental variation. The importance of phenotypic plasticity in natural populations and its contribution to phenotypic evolution during rapid environmental change is widely debated. This study shows that thermal plasticity of gene expression in natural populations is a key component of its adaptation: evolution to novel thermal environments increases ancestral plasticity rather than mean genetic expression. The evolution of plasticity in gene expression was determined by conducting laboratory natural selection on a Drosophila simulans population in hot and cold environments. After more than 60 generations in the hot environment, 325 genes evolved a change in plasticity relative to the natural ancestral population. Plasticity increased in 75% of these genes, which were strongly enriched for several well-defined functional categories (e.g. chitin metabolism, glycolysis and oxidative phosphorylation). Furthermore, this study showed that plasticity in gene expression of populations exposed to different temperatures is rather similar across species. It is concluded that most of the ancestral plasticity can evolve further in more extreme environments (Mallard, 2020).

    A clinal polymorphism in the insulin signaling transcription factor foxo contributes to life-history adaptation in Drosophila

    A fundamental aim of adaptation genomics is to identify polymorphisms that underpin variation in fitness traits. In D. melanogaster latitudinal life-history clines exist on multiple continents and make an excellent system for dissecting the genetics of adaptation. Previous work has identified numerous clinal SNPs in insulin/insulin-like growth factor signaling (IIS), a pathway known from mutant studies to affect life history. However, the effects of natural variants in this pathway remain poorly understood. This study investigated how two clinal alternative alleles at foxo, a transcriptional effector of IIS, affect fitness components (viability, size, starvation resistance, fat content). This polymorphism from the North American cline was assessed by reconstituting outbred populations, fixed for either the low- or high-latitude allele, from inbred DGRP lines. Since diet and temperature modulate IIS, alleles were phenotyped across two temperatures (18 ° C, 25 ° C) and two diets differing in sugar source and content. Consistent with clinal expectations, the high-latitude allele conferred larger body size and reduced wing loading. Alleles also differed in starvation resistance and expression of InR, a transcriptional target of FOXO. Allelic reaction norms were mostly parallel, with few GxE interactions. Together, these results suggest that variation in IIS makes a major contribution to clinal life-history adaptation ( , ).

    Temperature, rainfall and wind variables underlie environmental adaptation in natural populations of Drosophila melanogaster

    While several studies in a diverse set of species have shed light on the genes underlying adaptation, knowledge on the selective pressures that explain the observed patterns lags behind. Drosophila melanogaster is a valuable organism to study environmental adaptation because this species originated in Southern Africa and has recently expanded worldwide, and also because it has a functionally well-annotated genome. This work aimed to decipher which environmental variables are relevant for adaptation of D. melanogaster natural populations in Europe and North America. 36 whole-genome pool-seq samples of D. melanogaster natural populations were ezamined, collected in 20 European and 11 North American locations. The BayPass software was used to identify SNPs and transposable elements showing signature of adaptive differentiation across populations, as well as significant associations with 59 environmental variables related to temperature, rainfall, evaporation, solar radiation, wind, daylight hours, and soil type. Besides temperature and rainfall, wind related variables are also relevant for D. melanogaster environmental adaptation. Interestingly, 23% to 51% of the genes that showed significant associations with environmental variables were not found overly differentiated across populations. Besides SNPs, ten reference transposable element insertions associated with environmental variables were identified. These results showed that genome-environment association analysis can identify adaptive genetic variants that are undetected by population differentiation analysis while also allowing the identification of candidate environmental drivers of adaptation (Bogaerts-Marquez, 2020).

    Multiple mechanisms drive genomic adaptation to extreme O(2) levels in Drosophila melanogaster

    To detect the genomic mechanisms underlying evolutionary dynamics of adaptation in sexually reproducing organisms, this study analyze multigenerational whole genome sequences of Drosophila melanogaster adapting to extreme O(2) conditions over an experiment conducted for nearly two decades. Methods to analyze time-series genomics data and predict adaptive mechanisms were developed. This study report a remarkable level of synchronicity in both hard and soft selective sweeps in replicate populations as well as the arrival of favorable de novo mutations that constitute a few asynchronized sweeps. Additionally direct experimental observations were made of rare recombination events that combine multiple alleles on to a single, better-adapted haplotype. Based on the analyses of the genes in genomic intervals, this study provides a deeper insight into the mechanisms of genome adaptation that allow complex organisms to survive harsh environments (Iranmehr, 2021).

    The genomic architecture of adaptation to larval malnutrition points to a trade-off with adult starvation resistance in Drosophila

    Periods of nutrient shortage impose strong selection on animal populations. Experimental studies of genetic adaptation to nutrient shortage largely focus on resistance to acute starvation at adult stage; it is not clear how conclusions drawn from these studies extrapolate to other forms of nutritional stress. The genomic signature of adaptation to chronic juvenile malnutrition was studied in six populations of Drosophila melanogaster evolved for 150 generations on an extremely nutrient-poor larval diet. Comparison with control populations evolved on standard food revealed repeatable genomic differentiation between the two set of population, involving >3,000 candidate SNPs forming >100 independently evolving clusters. The candidate genomic regions were enriched in genes implicated in hormone, carbohydrate, and lipid metabolism, including some with known effects on fitness-related life-history traits. Rather than being close to fixation, a substantial fraction of candidate SNPs segregated at intermediate allele frequencies in all malnutrition-adapted populations. This, together with patterns of among-population variation in allele frequencies and estimates of Tajima's D, suggests that the poor diet results in balancing selection on some genomic regions. Candidate genes for tolerance to larval malnutrition showed a high overlap with genes previously implicated in acute starvation resistance. However, adaptation to larval malnutrition in this study was associated with reduced tolerance to acute adult starvation. Thus, rather than reflecting synergy, the shared genomic architecture appears to mediate an evolutionary trade-off between tolerances to these two forms of nutritional stress (Kawecki, 2021).

    Male fertility thermal limits predict vulnerability to climate warming

    Forecasting which species/ecosystems are most vulnerable to climate warming is essential to guide conservation strategies to minimize extinction. Tropical/mid-latitude species are predicted to be most at risk as they live close to their upper critical thermal limits (CTLs). However, these assessments assume that upper CTL estimates, such as CTmax, are accurate predictors of vulnerability and ignore the potential for evolution to ameliorate temperature increases. This study used experimental evolution to assess extinction risk and adaptation in tropical and widespread Drosophila species. Tropical species were found to succumb to extinction before widespread species. Male fertility thermal limits, which are much lower than CTmax, are better predictors of species' current distributions and extinction in the laboratory. Little evidence was found of adaptive responses to warming in any species. These results suggest that species are living closer to their upper thermal limits than currently presumed and evolution/plasticity are unlikely to rescue populations from extinction (van Heerwaarden, 2021).

    Parallel and Population-specific Gene Regulatory Evolution in Cold-Adapted Fly Populations

    Changes in gene regulation at multiple levels may comprise an important share of the molecular changes underlying adaptive evolution in nature. However, few studies have assayed within- and between-population variation in gene regulatory traits at a transcriptomic scale, and therefore inferences about the characteristics of adaptive regulatory changes have been elusive. This study assessed quantitative trait differentiation in gene expression levels and alternative splicing (intron usage) between three closely-related pairs of natural populations of Drosophila melanogaster from contrasting thermal environments that reflect three separate instances of cold tolerance evolution. The cold-adapted populations were known to show population genetic evidence for parallel evolution at the SNP level, and this study found evidence for parallel expression evolution between them, with stronger parallelism at larval and adult stages than for pupae. A flexible method was implemented to estimate cis- versus trans-encoded contributions to expression or splicing differences at the adult stage. The apparent contributions of cis- versus trans-regulation to adaptive evolution vary substantially among population pairs. While two of three population pairs show a greater enrichment of cis-regulatory differences among adaptation candidates, trans-regulatory differences are more likely to be implicated in parallel expression changes between population pairs. Genes with significant cis-effects are enriched for signals of elevated genetic differentiation between cold- and warm-adapted populations, suggesting that they are potential targets of local adaptation. These findings expand knowledge of adaptive gene regulatory evolution and the ability to make inferences about this important and widespread process (Huang, 2021).

    The effects of adaptation to urea on feeding rates and growth in Drosophila larvae

    A collection of forty populations were used to study the phenotypic adaptation of Drosophila melanogaster larvae to urea-laced food. Fifteen populations subjected to direct selection for urea tolerance and five controls were studied. In addition, another twenty populations were studied that had not been exposed to urea but were subjected to stress or demographic selection. This study describes the differentiation in these population for six phenotypes: (1) larval feeding rates, (2) larval viability in urea-laced food, (3) larval development time in urea-laced food, (4) adult starvation times, (5) adult desiccation times, and (6) larval growth rates. No significant differences were observed for desiccation resistance. The demographically/stress-selected populations had longer times to starvation than urea-selected populations. The urea-adapted populations showed elevated survival and reduced development time in urea-laced food relative to the control and nonadapted populations. The urea-adapted populations also showed reduced larval feeding rates relative to controls. This study showed that there is a strong linear relationship between feeding rates and growth rates at the same larval ages feeding rates were measured. This suggests that feeding rates are correlated with food intake and growth. This relationship between larval feeding rates, food consumption, and efficiency has been postulated to involve important trade-offs that govern larval evolution in stressful environments. These results support the idea that energy allocation is a central organizing theme in adaptive evolution (Bitner, 2021).

    Host plant shift differentially alters olfactory sensitivity in female and male Drosophila mojavensis

    Animals may vary in their utilization of plants depending on plant availability, and also on the sex of the animal. Evolutionary adaptations may arise, particularly in specialist animals to the chemistry of the host plants, and these adaptations may differ between the sexes due to differences in their interactions with the plants. Drosophila mojavensis uses different host cacti across its range, and volatile chemicals emitted by the host are the primary cue for host plant identification. This study measured responses of individual olfactory sensory neurons to a large suite of odorants across males and females of the two southern D. mojavensis populations. A switch in host plant was shown to be accompanied by changes in the olfactory system, but the effect of this switch is minor compared to that of sex. That is, differences were observed in olfactory receptor neuron specificity and sensitivity to odorants between sexes, and to a lesser extent between populations. The majority of sensory differences are restricted to only three of the 17 sensory neurons measured. Further, numerous differences between sexes were found that only occur within one population, i.e., sex-by-population interactions (Ammagarahalli, 2021).

    Phenotypic and Transcriptomic Responses to Stress Differ According to Population Geography in an Invasive Species

    Adaptation to rapid environmental changes must occur within a short-time scale. In this context, studies of invasive species may provide insights into the underlying mechanisms of rapid adaptation as these species have repeatedly encountered and adapted to novel environmental conditions. This study investigated how invasive and noninvasive genotypes of Drosophila suzukii deal with oxidative stress at the phenotypic and molecular levels. Also studied was the impact of transposable element (TE) insertions on the gene expression in response to stress. Results show that flies from invasive areas (France and the United States) live longer in natural conditions than the ones from native Japanese areas. As expected, lifespan for all genotypes was significantly reduced following exposure to paraquat, but this reduction varied among genotypes (genotype-by-environment interaction) with invasive genotypes appearing more affected by exposure than noninvasive ones. A transcriptomic analysis of genotypes upon paraquat treatment detected many genes differentially expressed (DE). Although a small core set of genes were DE in all genotypes following paraquat exposure, much of the response of each genotype was unique. Moreover, it was shown that TEs were not activated after oxidative stress and DE genes were significantly depleted of TEs. In conclusion, it is likely that transcriptomic changes are involved in the rapid adaptation to local environments. This study provides new evidence that in the decade since the invasion from Asia, the sampled genotypes in Europe and the United States of D. suzukii diverged from the ones from the native area regarding their phenotypic and genomic response to oxidative stress (Marin, 2021).

    No evidence for short-term evolutionary response to a warming environment in Drosophila

    Adaptive evolution is key in mediating responses to global warming and may sometimes be the only solution for species to survive. Such evolution will expectedly lead to changes in the populations' thermal reaction norm and improve their ability to cope with stressful conditions. Conversely, evolutionary constraints might limit the adaptive response. This study tests these expectations by performing a real-time evolution experiment in historically differentiated Drosophila subobscura populations. The phenotypic change was addressed after nine generations of evolution in a daily fluctuating environment with average constant temperature, or in a warming environment with increasing average and amplitude temperature across generations. The results showed that (1) evolution under a global warming scenario does not lead to a noticeable change in the thermal response; (2) historical background appears to be affecting responses under the warming environment, particularly at higher temperatures; and (3) thermal reaction norms are trait dependent: although lifelong exposure to low temperature decreases fecundity and productivity but not viability, high temperature causes negative transgenerational effects on productivity and viability, even with high fecundity. These findings in such an emblematic organism for thermal adaptation studies raise concerns about the short-term efficiency of adaptive responses to the current rising temperatures (Santos, 2021).

    Evolution of chemosensory and detoxification gene families across herbivorous Drosophilidae
    Herbivorous insects are exceptionally diverse, accounting for a quarter of all known eukaryotic species, but the genomic basis of adaptations that enabled this dietary transition remains poorly understood. Many studies have suggested that expansions and contractions of chemosensory and detoxification gene families-genes directly mediating interactions with plant chemical defenses-underlie successful plant colonization. However, this hypothesis has been challenging to test because the origins of herbivory in many insect lineages are ancient (>150 million years ago (mya)), obscuring genomic evolutionary patterns. This study characterized chemosensory and detoxification gene family evolution across Scaptomyza, a genus nested within Drosophila that includes a recently derived (>15 mya) herbivore lineage of mustard (Brassicales) specialists and carnation (Caryophyllaceae) specialists, and several nonherbivorous species. Comparative genomic analyses revealed that herbivorous Scaptomyza has among the smallest chemosensory and detoxification gene repertoires across 12 drosophilid species surveyed. Rates of gene turnover averaged across the herbivore clade were significantly higher than background rates in over half of the surveyed gene families. However, gene turnover was more limited along the ancestral herbivore branch, with only gustatory receptors and odorant-binding proteins experiencing strong losses. The genes most significantly impacted by gene loss, duplication, or changes in selective constraint were those involved in detecting compounds associated with feeding on living plants (bitter or electrophilic phytotoxins) or their ancestral diet (fermenting plant volatiles). These results provide insight into the molecular and evolutionary mechanisms of plant-feeding adaptations and highlight gene candidates that have also been linked to other dietary transitions in Drosophila (Pelaez, 2023). >

    The Interplay Between Developmental Stage and Environment Underlies the Adaptive Effect of a Natural Transposable Element Insertion

    Establishing causal links between adaptive mutations and ecologically relevant phenotypes is key to understanding the process of adaptation, which is a central goal in evolutionary biology with applications for conservation, medicine, and agriculture. Yet despite recent progress, the number of identified causal adaptive mutations remains limited. Linking genetic variation to fitness-related effects is complicated by gene-by-gene and gene-by-environment interactions, among other processes. Transposable elements, which are often ignored in the quest for the genetic basis of adaptive evolution, are a genome-wide source of regulatory elements across organisms that can potentially result in adaptive phenotypes. This work combined gene expression, in vivo reporter assays, CRISPR/Cas9 genome editing, and survival experiments to characterize in detail the molecular and phenotypic consequences of a natural Drosophila melanogaster transposable element insertion: the roo solo-LTR FBti0019985. This transposable element provides an alternative promoter to the transcription factor Lime, involved in cold- and immune-stress responses. The effect of FBti0019985 on Lime expression were found to depend on the interplay between the developmental stage and environmental condition. A causal link between the presence of FBti0019985 and increased survival to cold- and immune-stress was established. The results exemplify how several developmental stages and environmental conditions need to be considered to characterize the molecular and functional effects of a genetic variant, and add to the growing body of evidence that transposable elements can induce complex mutations with ecologically relevant effects (Merenciano, 2023).

    Rapid but narrow - Evolutionary adaptation and transcriptional response of Drosophila melanogaster to toxic mould

    Insects have adapted to a multitude of environmental conditions, including the presence of xenobiotic noxious substances. Environmental microorganisms, particularly rich on ephemeral resources, employ these noxious chemicals in a chemical warfare against predators and competitors, driving co-evolutionary adaptations. In order to analyse how environmental microbes may be driving such evolutionary adaptations, this study experimentally evolved Drosophila melanogaster populations by exposing larvae to the toxin-producing mould Aspergillus nidulans that infests the flies' breeding substrate. To disentangle the effects of the mycotoxin Sterigmatocystin from other substrate modifications inflicted by the mould, the following four selection regimes were used: (i) control without fungus, (ii) A. nidulans wild type, (iii) a mutant of A. nidulans ΔlaeA with impaired toxin production, (iv) synthetic Sterigmatocystin. Experimental evolution was carried out in five independent D. melanogaster populations each, for a total of 11 generations. This evolution experiment was further combined with transcriptome analysis to identify evolutionary shifts in gene expression due to the selection regimes and mould confrontation. Populations that evolved in presence of the toxin-producing mould or the pure mycotoxin rapidly adapted to the respective conditions and showed higher viability in subsequent confrontations. Yet, mycotoxin-selected populations had no advantage in A. nidulans wild type confrontation. Moreover, distinctive changes in gene expression related to the selection-regime contrast were only associated with the toxin-producing-fungus regime and comprised a narrow set of genes. Thus, it needs the specific conditions of the selection agent to enable adaptation to the fungus (Trienens, 2023).

    Experimental Evidence That Phenotypic Evolution but Not Plasticity Occurs along Genetic Lines of Least Resistance in Homogeneous Environments

    Genetic correlations concentrate genetic variation in certain directions of the multivariate phenotype. Adaptation and, under some models, plasticity is expected to occur in the direction of the phenotype containing the greatest amount of genetic variation (g(max)). However, this may hinge on environmental heterogeneity, which can affect patterns of genetic variation. This study used experimental evolution to test whether plasticity and phenotypic evolution follow g(max) during adaptation to environments that varied in environmental heterogeneity. For >25 generations, Drosophila melanogaster populations were exposed to six homogeneous or spatially and temporally heterogeneous treatments involving hot (25°C) and cold (16°C) temperatures. Five wing traits were assayed in both temperatures. Wing morphology diverged between populations evolving in homogeneous hot and cold temperatures in a direction of the phenotype containing a large proportion of genetic variance and that aligned closely with g(max) at 16°C but not at 2°C. Spatial heterogeneity produced an intermediate phenotype, which was associated with similar genetic variance across assay temperatures compared with all other treatments. Surprisingly, plasticity across assay temperatures was in a different direction to phenotypic evolution and aligned better with maternal variance than g(max). Together, these results provide experimental evidence for evolution along genetic lines of least resistance in homogeneous environments but no support for predicting plastic responses from the orientation of genetic variation. These results also suggest that spatial heterogeneity could maintain genetic variation that increases the stability of genetic variance across environments (Walter, 2023).

    Differential adaptive RNA editing signals between insects and plants revealed by a new measurement termed haplotype diversity

    C-to-U RNA editing in plants is believed to confer its evolutionary adaptiveness by reversing unfavorable DNA mutations. This "restorative hypothesis" has not yet been tested genome-wide. In contrast, A-to-I RNA editing in insects like Drosophila and honeybee is already known to benefit the host by increasing proteomic diversity in a spatial-temporal manner (namely "diversifying hypothesis"). This study profiled the RNA editomes of multiple tissues of Arabidopsis thaliana, Drosophila melanogaster, and Apis melifera. The haplotype diversity (HD) of RNA molecules was unprecedentedly defined based on nonsynonymous editing events (recoding sites). Signals of adaptation is confirmed in Arabidopsis by observing higher frequencies and levels at nonsynonymous editing sites over synonymous sites. Compared to A-to-I recoding sites in Drosophila, the C-to-U recoding sites in Arabidopsis show significantly lower HD, presumably due to the stronger linkage between C-to-U events. It is concluded that C-to-U RNA editing in Arabidopsis is adaptive but it is not designed for diversifying the proteome like A-to-I editing in Drosophila. Instead, C-to-U recoding sites resemble DNA mutations. These observation supports the restorative hypothesis of plant C-to-U editing which claims that editing is used for fixing unfavorable genomic sequences (Duan, 2023).

    Regulation of gene expression and RNA editing in Drosophila adapting to divergent microclimates

    Determining the mechanisms by which a species adapts to its environment is a key endeavor in the study of evolution. In particular, relatively little is known about how transcriptional processes are fine-tuned to adjust to different environmental conditions. This study examined Drosophila melanogaster from 'Evolution Canyon' in Israel, which consists of two opposing slopes with divergent microclimates. Several hundred differentially expressed genes and dozens of differentially edited sites were identified between flies from each slope; these changes were correlate with genetic differences, and CRISPR mutagenesis was used to validate that an intronic SNP in prominin regulates its editing levels. It was also demonstrated that while temperature affects editing levels at more sites than genetic differences, genetically regulated sites tend to be less affected by temperature. This work shows the extent to which gene expression and RNA editing differ between flies from different microclimates, and provides insights into the regulation responsible for these differences (Yablonovitch, 2017).

    This study analyzed the genomes, transcriptomes, and editomes of individual fly lines from the two slopes of Evolution Canyon, building upon previous studies examining Drosophila from this canyon1. Evolution Canyon is uniquely suited for studying the biodiversity, evolution and adaptation of organisms that live in relatively close proximity to each other, and is a potential model for incipient sympatric speciation. Although genetic and gene expression differences have been discovered previously in flies from different environments, most studies have examined fly populations at different latitudinal clines, and many signatures of adaptation found so far may be related to migration out of Africa. This is the first study to systematically examine gene expression and RNA editing differences in flies from different microclimates (Yablonovitch, 2017).

    Several candidate genes were identified whose expression may play an adaptive role in the Evolution Canyon flies. The most striking of these are the Glutathione S-transferase genes, which show global under-expression in the NFS1 (north facing slope 1) flies compared to the SFS (south facing slope), and tend to be under-expressed in the NFS2 flies compared to the SFS as well. These detoxification enzymes metabolize antioxidants, and their decreased expression in the NFS1 and NFS2 relative to the SFS flies may be related to the decreased sun exposure, as there is 200–800% more solar radiation on the SFS18. It is interesting to note that a previous study examining flies from Evolution Canyon showed enrichment of glutathione metabolism and transferase activity in genomic regions with evidence of inter-slope differentiating selection. In addition, some Glutathione S-transferase genes have been shown to have significantly decreased expression in European flies compared to African flies in brain tissue. Other genes involved in pigmentation, stress response, digestion, and chitin-related processes also showed significant gene expression differences between flies from the two slopes. Future studies will be needed to address the potential adaptive role of the expression of these genes, and any regulatory mutations that are responsible for these gene expression changes (Yablonovitch, 2017).

    A strong connection was shown between the genetic differences and the gene expression and RNA editing differences of the flies from the two slopes. This implies that, despite the flies being collected from Evolution Canyon years prior to these experiments, genetic regulation of gene expression and RNA editing still persists in the isofemale lines. In particular, it was confirmed that an intronic SNP regulates the editing levels of two sites in the prominin transcript, although the exact amount of editing level regulation contributed by the SNP could not be determined, since a CRISPR-associated PAM mutation was made in the same mutant. Since both the editing sites and the intronic SNP are conserved in many Drosophila species, and since most of the NFS1 lines contain the mutant allele that causes a decrease in editing, it is possible that the less stressful NFS environment decreased the strength of selection against this mutation. Although an editing-related prominin phenotype has not been identified, previous studies examining RNA editing evolution in different Drosophila species have demonstrated evidence of selection, especially for conserved, non-synonymous site. As the sites in prominin dealt with in this study are likewise conserved and code for non-synonymous amino acid changes, it's still possible that they play an adaptive role (Yablonovitch, 2017).

    For RNA editing, both population genetic differences and environmental differences were capable of regulating editing between flies from the two slopes, and that the regulation seems to act through changing the structural stability of the RNA editing substrate. A change in environment regulates editing to a large extent for dozens of sites, most likely by affecting the stability of many RNA structures simultaneously. In contrast, genetic regulation is more site-specific, likely due to particular SNPs nearby editing sites which change the stability of the RNA structure containing those sites. This result is also supported by previous studies that examined editing level differences between and within Drosophila species. Population genetic differences in editing tend to be maintained regardless of the environment in which they were measure, suggesting that genetic regulation may be more influential than environmental regulation of these sites. One 3' UTR site in the falafel transcript was found that exhibits a genotype-environment interaction between the NFS1 and SFS fly populations, as well as several non-synonymous sites in the cacophony transcript between the NFS2 and SFS fly populations. Future studies will be needed in different populations and environments to determine whether these trends in editing happen universally (Yablonovitch, 2017).

    To conclude, this study found surprising connections between genetics, gene expression, and RNA editing in flies from the distinct microclimates of Evolution Canyon. By sequencing individual lines, it was possuble to show a clear correspondence between genotype and gene expression differences between flies from the two opposing slopes, some of which may be important for adaptation. In addition, both genetic and environmental regulation of RNA editing was observed in these flies, though the two modes of regulation seem to operate mostly independently of each other. This study sets the stage for future examinations of the regulation of adaptive gene expression and RNA editing differences, not only in other fly populations, but in other species as well (Yablonovitch, 2017).

    Acuity and summation strategies differ in vinegar and desert fruit flies

    An animal's vision depends on terrain features that limit the amount and distribution of available light. Approximately 10,000 years ago, vinegar flies (Drosophila melanogaster) transitioned from a single plant specialist into a cosmopolitan generalist. Much earlier, desert flies (D. mojavensis) colonized the New World, specializing on rotting cactuses in southwest North America. Their desert habitats are characteristically flat, bright, and barren, implying environmental differences in light availability. This study demonstrated differences in eye morphology and visual motion perception under three ambient light levels. Reducing ambient light from 35 to 18 cd/m(2) causes sensitivity loss in desert but not vinegar flies. However, at 3 cd/m(2), desert flies sacrifice spatial and temporal acuity more severely than vinegar flies to maintain contrast sensitivity. These visual differences help vinegar flies navigate under variably lit habitats around the world and desert flies brave the harsh desert while accommodating their crepuscular lifestyle (Currea, 2022).

    Intermolecular Interactions Drive Protein Adaptive and Coadaptive Evolution at Both Species and Population Levels

    Proteins are the building blocks for almost all the functions in cells. Understanding the molecular evolution of proteins and the forces that shape protein evolution is essential in understanding the basis of function and evolution. Previous studies have shown that adaptation frequently occurs at the protein surface, such as in genes involved in host-pathogen interactions. However, it remains unclear whether adaptive sites are distributed randomly or at regions associated with particular structural or functional characteristics across the genome, since many proteins lack structural or functional annotations. This study sought to tackle this question by combining large-scale bioinformatic prediction, structural analysis, phylogenetic inference, and population genomic analysis of Drosophila protein-coding genes. Protein sequence adaptation was found to be more relevant to function-related rather than structure-related properties. Interestingly, intermolecular interactions contribute significantly to protein adaptation. Intermolecular interactions, such as physical interactions, may play a role in the coadaptation of fast-adaptive proteins. It was found that strongly differentiated amino acids across geographic regions in protein-coding genes are mostly adaptive, which may contribute to the long-term adaptive evolution. This strongly indicates that a number of adaptive sites tend to be repeatedly mutated and selected throughout evolution in the past, present, and maybe future. These results highlight the important roles of intermolecular interactions and coadaptation in the adaptive evolution of proteins both at the species and population levels (Peng, 2022).

    Direct observation of adaptive tracking on ecological time scales in Drosophila

    Direct observation of evolution in response to natural environmental change can resolve fundamental questions about adaptation, including its pace, temporal dynamics, and underlying phenotypic and genomic architecture. This study tracked the evolution of fitness-associated phenotypes and allele frequencies genome-wide in 10 replicate field populations of Drosophila melanogaster over 10 generations from summer to late fall. Adaptation was evident over each sampling interval (one to four generations), with exceptionally rapid phenotypic adaptation and large allele frequency shifts at many independent loci. The direction and basis of the adaptive response shifted repeatedly over time, consistent with the action of strong and rapidly fluctuating selection. Overall, clear phenotypic and genomic evidence were found of adaptive tracking occurring contemporaneously with environmental change, thus demonstrating the temporally dynamic nature of adaptation (Rudman, 2022).

    Strong evidence for the adaptive walk model of gene evolution in Drosophila and Arabidopsis

    Understanding the dynamics of species adaptation to their environments has long been a central focus of the study of evolution. Theories of adaptation propose that populations evolve by "walking" in a fitness landscape. This "adaptive walk" is characterised by a pattern of diminishing returns, where populations further away from their fitness optimum take larger steps than those closer to their optimal conditions. Hence, it is expected that young genes evolve faster and experience mutations with stronger fitness effects than older genes because they are further away from their fitness optimum. Testing this hypothesis, however, constitutes an arduous task. Young genes are small, encode proteins with a higher degree of intrinsic disorder, are expressed at lower levels, and are involved in species-specific adaptations. Since all these factors lead to increased protein evolutionary rates, they could be masking the effect of gene age. While controlling for these factors, this study used population genomic data sets of Arabidopsis and Drosophila and estimated the rate of adaptive substitutions across genes from different phylostrata. A gene's evolutionary age was found to significantly impact the molecular rate of adaptation. Moreover, it was observed that substitutions in young genes tend to have larger physicochemical effects. This study, therefore, provides strong evidence that molecular evolution follows an adaptive walk model across a large evolutionary timescale (Moutinho, 2022).

    Distinct signals of clinal and seasonal allele frequency change at eQTLs in Drosophila melanogaster

    Populations of short-lived organisms can respond to spatial and temporal environmental heterogeneity through local adaptation. Local adaptation can be reflected on both phenotypic and genetic levels, and it has been documented in many organisms. Although complex fitness-related phenotypes have been shown to vary across latitudinal clines and seasons in similar ways in Drosophila melanogaster populations, the comparative signals of local adaptation across space and time remain poorly understood. This study examined patterns of allele frequency change across a latitudinal cline and between seasons at previously reported expression quantitative trait loci (eQTLs). eQTLs were divided into groups by using differential expression profiles of fly populations collected across latitudinal clines or exposed to different environmental conditions. In general, eQTLs were found to be enriched for clinally varying polymorphisms, and these eQTLs changed in frequency in concordant ways across the cline and in response to starvation and chill-coma. The enrichment of eQTLs among seasonally varying polymorphisms is more subtle, and the direction of allele frequency change at eQTLs appears to be somewhat idiosyncratic. Taken together, it is suggested that clinal adaptation at eQTLs is at least partially distinct from seasonal adaptation (Yu, 2022).

    Maximum SNP FST outperforms full-window statistics for detecting soft sweeps in local adaptation

    Local adaptation can lead to elevated genetic differentiation at the targeted genetic variant and nearby sites. Selective sweeps come in different forms, and depending on the initial and final frequencies of a favored variant, very different patterns of genetic variation may be produced. If local selection favors an existing variant that had already recombined onto multiple genetic backgrounds, then the width of elevated genetic differentiation (high FST) may be too narrow to detect using a typical windowed genome scan, even if the targeted variant becomes highly differentiated. Therefore a simulation approach was used to investigate the power of SNP-level FST (specifically, the maximum SNP FST value within a window, or FST_MaxSNP) to detect diverse scenarios of local adaptation, and compared it against whole-window FST and the Comparative Haplotype Identity statistic. It was found that FST_MaxSNP had superior power to detect complete or mostly complete soft sweeps, but lesser power than full-window statistics to detect partial hard sweeps. Nonetheless, the power of FST_MaxSNP depended highly on sample size, and confident outliers depend on robust precautions and quality control. To investigate the relative enrichment of FST_MaxSNP outliers from real data, the two FST statistics were applied to a panel of Drosophila melanogaster populations. FST_MaxSNP had a genome-wide enrichment of outliers compared to demographic expectations, and though it yielded a lesser enrichment than window FST, it detected mostly unique outlier genes and functional categories. These results suggest that FST_MaxSNP is highly complementary to typical window-based approaches for detecting local adaptation, and merits inclusion in future genome scans and methodologies (da Silva Ribeiro, 2022).

    Drosophila melanogaster hosts coevolving with Pseudomonas entomophila pathogen show sex-specific patterns of local adaptation

    In spatially structured populations, local adaptation improves organisms' fitness in their native environment. Hosts and pathogens can rapidly adapt to their local antagonist. Since males and females can differ in their immunocompetence, the patterns of local adaptation can be different between the sexes. However, there is little information about sex differences in local adaptation in host-pathogen systems. This study experimentally coevolved four different replicate populations of Drosophila melanogaster (host) and Pseudomonas entomophila (pathogen) along with appropriate controls. The four host-pathogen coevolution populations were used to investigate the occurrence of local adaptation separately in males and females of the coevolving hosts. Local adaptation was also assessed in pathogens. A reciprocal infection experiment was set up where each of the four coevolving hosts were infected with their local pathogen or non-local pathogens from the other three replicate populations. Overall, male and female hosts had better survivorship when infected with local pathogens, indicating that they were locally adapted. Interestingly, males were more susceptible to non-local pathogens compared to females. In addition, no fecundity cost was found in females infected with either local or non-local pathogens. No evidence was found of local adaptation among the pathogens. This study showed sex-specific adaptation in the coevolving hosts where female hosts had a broader response against allopatric coevolving pathogens with no cost in fecundity. Thus, these results might suggest a novel mechanism that can maintain variation in susceptibility in spatially structured populations (Ahlawat, 2022).

    A single amino acid polymorphism in natural Metchnikowin alleles of Drosophila results in systemic immunity and life history tradeoffs

    Previous work demonstrated that one Antimicrobial peptide, Metchikowin (Mtk), has a single residue that segregates as either proline (P) or arginine (R) in populations of four different Drosophila species, some of which diverged more than 10 million years ago. The recurrent finding of this polymorphism regardless of geography or host species, coupled with evidence of balancing selection in Drosophila AMPs, suggest there is a distinct functional importance to each allele. To assess their functional differences, D. melanogaster lines were created with the P allele, R allele, or Mtk null mutation using CRISPR/Cas9 genome editing. This study report results from experiments assessing the two hypotheses using these lines. In males, testing of systemic immune responses to a repertoire of bacteria and fungi demonstrated that the R allele performs as well or better than the P and null alleles with most infections. With some pathogens, however, females show results in contrast with males where Mtk alleles either do not contribute to survival or where the P allele outperforms the R allele. In addition, measurements of life history traits demonstrate that the R allele is more costly in the absence of infection for both sexes. These results provide strong in vivo evidence that differential fitness with or without infection and sex-based functional differences in alleles may be adaptive mechanisms of maintaining immune gene polymorphisms in contrast with expectations of rapid evolution. Therefore, a complex interplay of forces including pathogen species and host sex may lead to balancing selection for immune genotypes. Strikingly, this selection may act on even a single amino acid polymorphism in an AMP (Perlmutter, 2023).

    Ecology-relevant bacteria drive the evolution of host antimicrobial peptides in Drosophila

    Antimicrobial peptides are host-encoded immune effectors that combat pathogens and shape the microbiome in plants and animals. However, little is known about how the host antimicrobial peptide repertoire is adapted to its microbiome. This study characterized the function and evolution of the Diptericin antimicrobial peptide family of Diptera. Using mutations affecting the two Diptericins (Dpt) of Drosophila melanogaster, the specific role of DptA for the pathogen Providencia rettgeri and DptB for the gut mutualist Acetobacter. The presence of DptA- or DptB-like genes across Diptera correlates with the presence of Providencia and Acetobacter in their environment. Moreover, DptA- and DptB-like sequences predict host resistance against infection by these bacteria across the genus Drosophila. This study explains the evolutionary logic behind the bursts of rapid evolution of an antimicrobial peptide family and reveals how the host immune repertoire adapts to changing microbial environments (Hanson, 2023).

    Experimental evolution of metabolism under nutrient restriction: enhanced amino acid catabolism and a key role of branched-chain amino acids

    Periodic food shortage is a common ecological stressor for animals, likely to drive physiological and metabolic adaptations to alleviate its consequences, particularly for juveniles that have no option but to continue to grow and develop despite undernutrition. This study examined changes in metabolism associated with adaptation to nutrient shortage, evolved by replicate Drosophila melanogaster populations maintained on a nutrient-poor larval diet for over 240 generations. In a factorial metabolomics experiment it was shown that both phenotypic plasticity and genetically-based adaptation to the poor diet involved wide-ranging changes in metabolite abundance; however, the plastic response did not predict the evolutionary change. Compared to nonadapted larvae exposed to the poor diet for the first time, the adapted larvae showed lower levels of multiple free amino acids in their tissues-and yet they grew faster. By quantifying accumulation of the nitrogen stable isotope (15)N it was shown that adaptation to the poor diet led to an increased use of amino acids for energy generation. This apparent "waste" of scarce amino acids likely results from the trade-off between acquisition of dietary amino acids and carbohydrates observed in these populations. The three branched-chain amino acids (leucine, isoleucine, and valine) showed a unique pattern of depletion in adapted larvae raised on the poor diet. A diet supplementation experiment demonstrated that these amino acids are limiting for growth on the poor diet, suggesting that their low levels resulted from their expeditious use for protein synthesis. These results demonstrate that selection driven by nutrient shortage not only promotes improved acquisition of limiting nutrients, but also has wide-ranging effects on how the nutrients are used. They also show that the abundance of free amino acids in the tissues does not, in general, reflect the nutritional condition and growth potential of an animal (Cavigliasso, 2023).

    Interplay between male quality and male-female compatibility across episodes of sexual selection

    The processes underlying mate choice profoundly influence the dynamics of sexual selection and the evolution of male sexual traits. Consistent preference for certain phenotypes may erode genetic variation in populations through directional selection, whereas divergent preferences (e.g., genetically compatible mates) provide one mechanism to maintain such variation. However, the relative contributions of these processes across episodes of selection remain unknown. Using Drosophila melanogaster, this study followed the fate of male genotypes, previously scored for their overall reproductive value and their compatibility with different female genotypes, across pre- and postmating episodes of selection. When pairs of competitor males differed in their intrinsic quality and their compatibility with the female, both factors influenced outcomes from mating success to paternity but to a varying degree between stages. These results add further dimensions to understanding of how the interactions between genotypes and forms of selection shape reproductive outcomes and ultimately reproductive trait evolution (Mahdjoub, 2023).

    Adaptive changes in energy reserves and effects of body melanization on thermal tolerance in Drosophila simulans

    Seasonally polyphenic types have been documented in many Drosophilids, which differ significantly during thermal stress. Although Drosophila simulans is a sibling species to Drosophila melanogaster, both thrive in the temperate and tropical climates, but various climatic factors are expected to impact their distribution and abundance. As a result, D. simulans may use phenotypic plasticity to adapt to colder and drier circumstances in temperate zones, although such studies are less known. The main aim of this study was to find a link between adaptive plasticity and thermal tolerance in D. simulans. Two morphs in D. simulans flies were characterized based on the abdominal melanization collected from the same locality and season, as this trait is highly associated with the larval developmental conditions. The results suggested that flies reared from dark and light morph showed significant differences in the basal level of proline, carbohydrates (trehalose, glycogen), and lipids (cuticular lipids and total body lipids) within simulated seasons and morph lineages in D. simulans flies. It was further shown that D. simulans reared from dark morph are better adapted to cold conditions, whereas light flies are more adapted to warm conditions. The flies, both from light and dark morph lineages, when reared at 15 °C, showed an increase in the level of total body lipids after acclimation at 0 °C but a decrease in the level of proline and carbohydrates (trehalose, glycogen). Heat acclimation increases glycogen levels in the flies from light morph lineage while decreases trehalose and proline (Tamang, 2022).

    Variation in mitochondrial DNA affects locomotor activity and sleep in Drosophila melanogaster

    Mitochondria are organelles that produce cellular energy in the form of ATP through oxidative phosphorylation, and this primary function is conserved among many taxa. Locomotion is a trait that is highly reliant on metabolic function and expected to be greatly affected by disruptions to mitochondrial performance. To this end, this study aimed to examine how activity and sleep vary between Drosophila melanogaster strains with different geographic origins, how these patterns are affected by mitochondrial DNA (mtDNA) variation, and how breaking up co-evolved mito-nuclear gene combinations affect the studied activity traits. The results demonstrate that Drosophila strains from different locations differ in sleep and activity, and that females are generally more active than males. By comparing activity and sleep of mtDNA variants introgressed onto a common nuclear background in cytoplasmic hybrid (cybrid) strains, it was possible to quantify the among-line variance attributable to mitochondrial DNA, and it was established that mtDNA variation affects both activity and sleep, in a sex-specific manner. Altogether this study highlights the important role that mitochondrial genome variation plays on organismal physiology and behaviour (Anderson, 2022).

    Phylogenomics provides insights into the evolution of cactophily and host plant shifts in Drosophila

    Cactophilic species of the Drosophila buzzatii cluster (repleta group) comprise an excellent model group to investigate genomic changes underlying adaptation to extreme climate conditions and host plants. In particular, these species form a tractable system to study the transition from chemically simpler breeding sites (like prickly pears of the genus Opuntia) to chemically more complex hosts (columnar cacti). This study reports four highly contiguous genome assemblies of three species of the buzzatii cluster. Based on this genomic data and inferred phylogenetic relationships, candidate taxonomically restricted genes (TRGs) likely involved in the evolution of cactophily and cactus host specialization were identified. Functional enrichment analyses of TRGs within the buzzatii cluster identified genes involved in detoxification, water preservation, immune system response, anatomical structure development, and morphogenesis. In contrast, processes that regulate responses to stress, as well as the metabolism of nitrogen compounds, transport, and secretion were found in the set of species that are columnar cacti dwellers. These findings are in line with the hypothesis that those genomic changes brought about key mechanisms underlying the adaptation of the buzzatii cluster species to arid regions in South America (Moreyra, 2023).

    Taste adaptations associated with host-specialization in the specialist Drosophila sechellia

    Chemosensory-driven hostplant specialization is a major force mediating insect ecological adaptation and speciation. Drosophila sechellia, a species endemic to the Seychelles islands, feeds and oviposits on Morinda citrifolia almost exclusively. This fruit is harmless to D. sechellia but toxic to other Drosophilidae, including the closely related generalists D. simulans and D. melanogaster, due to its high content of fatty acids. While several olfactory adaptations mediating D. sechellia's preference for its host have been uncovered, the role of taste has been much less examined. This study found that D. sechellia has reduced taste and feeding aversion to bitter compounds and host fatty acids that are aversive to D. melanogaster and D. simulans. The loss of aversion to canavanine, coumarin, and fatty acids arose in the D. sechellia lineage, as its sister species D. simulans showed responses akin to those of D. melanogaster. D. sechellia has increased taste and feeding responses towards M. citrifolia. These results are in line with D. sechellia's loss of genes encoding bitter gustatory receptors (GRs) in D. melanogaster. It was found that two gustatory receptor (GR) genes which are lost in D. sechellia, GR39a.a and GR28b.a, influence the reduction of aversive responses to some bitter compounds. Also, D. sechellia has increased appetite for a prominent host fatty acid compound that is toxic to its relatives. These results support the hypothesis that changes in the taste system, specifically a reduction of sensitivity to bitter compounds that deter generalist ancestors, contribute to the specialization of D. sechellia for its host (Reisenman, 2023).

    Slow and population specific evolutionary response to a warming environment

    Adaptation to increasingly warmer environments may be critical to avoid extinction. Whether and how these adaptive responses can arise is under debate. Though several studies have tackled evolutionary responses under different thermal selective regimes, very few have specifically addressed the underlying patterns of thermal adaptation under scenarios of progressive warming conditions. Also, considering how much past history affects such evolutionary response is critical. This study reports a long-term experimental evolution study addressing the adaptive response of Drosophila subobscura populations with distinct biogeographical history to two thermal regimes. The results showed clear differences between the historically differentiated populations, with adaptation to the warming conditions only evident in the low latitude populations. Furthermore, this adaptation was only detected after more than 30 generations of thermal evolution. These findings show some evolutionary potential of Drosophila populations to respond to a warming environment, but the response was slow and population specific, emphasizing limitations to the ability of ectotherms to adapt to rapid thermal shifts (Santos, 2023).

    Ethanol resistance in Drosophila melanogaster has increased in parallel cold-adapted populations and shows a variable genetic architecture within and between populations

    Understanding the genetic properties of adaptive trait evolution is a fundamental crux of biological inquiry that links molecular processes to biological diversity. Important uncertainties persist regarding the genetic predictability of adaptive trait change, the role of standing variation, and whether adaptation tends to result in the fixation of favored variants. This study used the recurrent evolution of enhanced ethanol resistance in Drosophila melanogaster during this species' worldwide expansion as a promising system to add to understanding of the genetics of adaptation. Elevated ethanol resistance was found to have evolved at least three times in different cooler regions of the species' modern range-not only at high latitude but also in two African high-altitude regions. Applying a bulk segregant mapping framework, this study found that the genetic architecture of ethanol resistance evolution differs substantially not only between the three resistant populations, but also between two crosses involving the same European population. Population genetic scans were applied for local adaptation within the quantitative trait locus regions, and potential contributions were found of genes with annotated roles in spindle localization, membrane composition, sterol and alcohol metabolism, and other processes. Simulation-based analyses were appleid that confirm the variable genetic basis of ethanol resistance and hint at a moderately polygenic architecture. However, these simulations indicate that larger-scale studies will be needed to more clearly quantify the genetic architecture of adaptive evolution and to firmly connect trait evolution to specific causative loci (Sprengelmeyer, 2021).

    Unique genetic signatures of local adaptation over space and time for diapause, an ecologically relevant complex trait, in Drosophila melanogaster

    Local adapation can result in variation in seasonal responses, but the genetic basis and evolutionary history of this variation remains elusive. Many insects, including Drosophila melanogaster, are able to undergo an arrest of reproductive development (diapause) in response to unfavorable conditions. In D. melanogaster, the ability to diapause is more common in high latitude populations, where flies endure harsher winters, and in the spring, reflecting differential survivorship of overwintering populations. Using a novel hybrid swarm-based genome wide association study, this study examined the genetic basis and evolutionary history of ovarian diapause. Outbred females were exposed to different temperatures and day lengths, ovarian development was characterized for over 2800 flies, and their complete, phased genomes were reconstructed. Diapause, scored at two different developmental cutoffs, was found to be modest heritability, and hundreds of SNPs associated with each of the two phenotypes were identified. Alleles associated with one of the diapause phenotypes tend to be more common at higher latitudes, but these alleles do not show predictable seasonal variation. The collective signal of many small-effect, clinally varying SNPs can plausibly explain latitudinal variation in diapause seen in North America. Alleles associated with diapause are segregating in Zambia, suggesting that variation in diapause relies on ancestral polymorphisms, and both pro- and anti-diapause alleles have experienced selection in North America. Finally, outdoor mesocosms were used to track diapause under natural conditions. Hybrid swarms reared outdoors were found to evolve increased propensity for diapause in late fall, whereas indoor control populations experienced no such change. These results indicate that diapause is a complex, quantitative trait with different evolutionary patterns across time and space (Erickson, 2020).

    Contingency in the convergent evolution of a regulatory network: Dosage compensation in Drosophila

    The repeatability or predictability of evolution is a central question in evolutionary biology and most often addressed in experimental evolution studies. This study inferred how genetically heterogeneous natural systems acquire the same molecular changes to address how genomic background affects adaptation in natural populations. In particular, advantage was taken of independently formed neo-sex chromosomes in Drosophila species that have evolved dosage compensation by co-opting the dosage-compensation male-specific lethal (MSL) complex to study the mutational paths that have led to the acquisition of hundreds of novel binding sites for the MSL complex in different species. This complex recognizes a conserved 21-bp GA-rich sequence motif that is enriched on the X chromosome, and newly formed X chromosomes recruit the MSL complex by de novo acquisition of this binding motif. Recently formed sex chromosomes were identified in the D. melanica and D. robusta species groups by genome sequencing and generate genomic occupancy maps of the MSL complex to infer the location of novel binding sites. Diverse mutational paths were utilized in each species to evolve hundreds of de novo binding motifs along the neo-X, including expansions of microsatellites and transposable element (TE) insertions. However, the propensity to utilize a particular mutational path differs between independently formed X chromosomes and appears to be contingent on genomic properties of that species, such as simple repeat or TE density. This establishes the 'genomic environment' as an important determinant in predicting the outcome of evolutionary adaptations (Ellison, 2019).

    This study took advantage of naturally occurring variation in sex chromosome karyotype in Drosophila species to study independent replicates of solving the same evolutionary challenge: to dosage compensate newly formed neo-X chromosomes by acquiring hundreds of MSL-binding sites in response to Y degeneration (Ellison, 2019).

    The independent acquisition of dosage compensation in Drosophila allows several important questions in evolutionary biology and gene regulation to be addressed: first, how repeatable is evolution? Evolutionary biologists have long debated the predictability of the evolutionary process. At one extreme, evolution could be highly idiosyncratic and unpredictable, since the survival of the fittest could occur along a great number of forking paths. Alternatively, constraints on evolution may force independent lineages to frequently converge on the same genetic solutions for the same evolutionary challenge. Second, how do regulatory networks evolve? And what is the contribution of TEs to regulatory evolution? Evolutionary innovations and adaptations often require rapid and concerted changes in regulation of gene expression at many loci. TEs constitute the most dynamic part of eukaryotic genomes, and the dispersal of TEs that contain a regulatory element may allow for the same regulatory motif to be recruited at many genomic locations, thereby drawing multiple genes into the same regulatory network. Third, what makes a binding motif functional? The genomes of complex organisms encompass megabases of DNA, and regulatory molecules must distinguish specific targets within this vast landscape. Regulatory factors typically identify their targets through sequence-specific interactions with the underlying DNA, but they typically bind only a fraction of the candidate genomic regions containing their specific target sequence motif. An unresolved mystery in regulatory evolution is what drives the specificity of binding to a subset of genomic regions that all appear to have a sequence that matches the consensus binding motif (Ellison, 2019).

    Several features make dosage compensation in Drosophila a promising system to tackle these questions. The genetic architecture for most adaptations -- especially those involving regulatory changes -- as well as the timing and exact selective forces driving them is generally little understood. In contrast, detailed knowledge is available of the molecular mechanism of dosage compensation in Drosophila. The cis- and trans-acting components of this regulatory network and the regulatory motif for targeting the MSL complex to the X are known. Clear expectations are available of which genomic regions should acquire dosage compensation and about the timing and the evolutionary forces that drive wiring of hundreds of genes into the dosage-compensation network on newly evolved X chromosomes. Specifically, Y degeneration is a general facet of sex chromosome evolution, creating selective pressures to up-regulate X-linked genes in males. Dosage compensation should thus only evolve on neo-X chromosomes whose neo-Y homologs have started to degenerate and should evolve simultaneously or shortly after substantial gene loss has occurred on the neo-Y. Indeed, comparative data in Drosophila support this model of dosage-compensation evolution. Drosophila species with partially eroded neo-Y chromosomes exist that have not yet evolved MSL-mediated dosage compensation, including D. busckii and D. albomicans, lending empirical support to the notion that dosage compensation evolves in response to Y degeneration and not the other way round. Thus, a refined understanding of how, when, why, and where dosage compensation in Drosophila evolves makes this an ideal model system to study the repeatability of evolution and the evolution of regulatory networks (Ellison, 2019).

    Results from evolution experiments indicate that although evolution is not identical in replicate populations, there is an important degree of predictability. Experimentally evolved populations under controlled, identical conditions consistently show parallelism in which mutations in certain genes are repeatedly selected. However, organisms adapting to similar environments are not genetically identical, but their genome instead carries the legacy of their unique evolutionary trajectory, raising the question of how genomic differences affect genetic parallelism (Ellison, 2019).

    Sex chromosome-autosome fusions have independently created neo-sex chromosomes in different Drosophila lineages. This provides everal independent replicates to study how, on the molecular level, evolution has solved the same adaptive challenge: acquiring hundreds of binding sites to recruit the MSL complex to newly formed X chromosomes. This allows quantification of how much variation there is, both within and between species, in the underlying mutational paths to acquire hundreds of MSL-binding sites on neo-X chromosomes and identify genomic contingencies that will influence the repeatability of evolutionary trajectories. Importantly, neo-sex chromosomes of Drosophila are evolutionarily young (between 0.1-15 MY old), which allows, in many cases, inferring of the causative mutations that have resulted in the gain of a regulatory element and decipher the evolutionary processes at work to draw hundreds of genes into a new regulatory network (Ellison, 2019).

    The results suggest that the evolution of MSL-binding sites is highly opportunistic but contingent on genomic background. In particular, each independently evolved neo-X chromosome was found to use a diverse set of mutational pathways to acquire MSL-binding sites on a new neo-X chromosome, ranging from microsatellite expansions to the utilization of presites to TE insertions. However, different lineages differ with regards to the frequency of which mutational paths are most often followed to acquire novel binding sites, and this propensity may depend on the genomic background. In particular, species found with the higher density of simple repeats are more prone to utilize expansions in GA microsatellites to gain a novel MSL-binding site. In contrast, D. robusta has an elevated TE density compared to its sibling species, and it was found that the dispersal of a TE has played an important role in the acquisition of MSL-binding sites on its neo-X chromosome. Thus, this suggests that the genomic background of a species predisposes it to evolve along a particular path, yet the evolutionary process is random and resourceful with regards to utilizing a variety of mutations to create novel MSL-binding sites. However, different phenotypes show drastic differences in their underlying genetic architecture, and the importance of genomic background likely differs among traits and (Ellison, 2019).

    Evolutionary innovations and adaptations often require rapid and concerted changes in regulation of gene expression at many loci. It has been suggested that TEs play a key role in rewiring regulatory networks, since the dispersal of TEs that contain a regulatory element may allow for the same regulatory motif to be recruited at many genomic locations. A handful of recent studies have implicated TEs as drivers of key evolutionary innovations, including placentation in mammals or rewiring the core regulatory network of human embryonic stem cells. While these studies demonstrate that TEs can, in principle, contribute to the creation or rewiring of regulatory networks, they do not address the question of how often regulatory elements evolve by TE insertions versus by other mutations. That is, the importance of TEs in contributing to regulatory evolution is not known. Quantification of the role of TEs would require a priori knowledge of how and when regulatory networks evolve and a detailed molecular understanding of which genes are being drawn into a regulatory network and how. As discussed above, these parameters are well understood for dosage compensation in flies (Ellison, 2019).

    Previous work in D. miranda has shown that a helitron TE was recruited into the dosage-compensation network at two independent time points. The younger 1.5-MY-old neo-X chromosome of D. miranda is in the process of evolving dosage compensation, and dozens of new CESs on this chromosome were created by insertions of the ISX element. The domesticated ISX TE gained a novel MRE motif by a 10-bp deletion in the ISY element, which is a highly abundant TE in the D. miranda genome. The remnants of a related (but different) TE at CES was found on the older neo-X of this species (which formed roughly 13-15 MY ago), but the TE was too eroded to reconstruct its evolutionary history. This study, identified another domesticated TE that was utilized to deliver MSL-binding sites to a newly formed neo-X chromosome, but no significant TE contribution was found for MSL-binding site evolution in two independent neo-X chromosomes (Ellison, 2019).

    The data shed light on the question of when TEs are expected to be important in regulatory evolution. For TEs to contribute to regulatory rewiring, two conditions have to be met: a regulatory element (or a progenitor sequence that can easily mutate into the required binding motif) needs to be present in the TE, and TE needs to be active in the genome (and not yet silenced by the host machinery). TEs undergo a characteristic life cycle in which they invade a new species (or escape the genome defense by mutation) and transpose until they are silenced by the host genome. Once a TE is robustly repressed, it no longer can serve as a vehicle to disperse regulatory elements, so the time window when a particular TE family can be domesticated is probably short and needs to coincide with a necessity to disperse regulatory motifs. A high TE burden does increase that chance, but at a cost: maintaining active TEs in the genome allows a rapid response to evolutionary challenges but also creates a major source of genomic mutation, illegitimate recombination, genomic rearrangements, and genome size inflation (Ellison, 2019).

    The current findings support this view of a TE tradeoff. The ISY element in D. miranda is the most highly abundant transposon in the D. miranda genome and is massively contributing to the degeneration of the neo-Y in this specie. Indeed, the genomic analysis has revealed >20,000 novel insertions of the ISY element on the neo-Y, often within genes. Yet, it contained a sequence that was only one mutational step away from a functional MSL-binding site (that is, a single 10-bp deletion), and domestication of this element allowed for the rapid dispersal of functional binding sites for the MSL complex along the neo-X. The domestication of the TE in D. robusta occurred too long ago for to reconstruct its exact evolutionary history and the potential damage its mobilization may have caused while it was active. However, consistent with a tradeoff that the host genome faces, it was found that D. robusta has a higher TE density than its sister species and also a considerably larger genome size, yet a TE contributed to wiring hundreds of genes into the dosage-compensation network on its neo-X (Ellison, 2019).

    Perhaps surprisingly, in many instances, it was not possible to detect specific mutations that would generate a novel MSL binding motif. Instead, it was found that functional MSL-binding sites are derived from presites containing the GA-rich motif that was already present in an ancestor in which the neo-X is autosomal and in which these sequences do not recruit the MSL complex. The MSL binding motif is only modestly enriched on the X chromosome compared to the autosomes (only approximately 2-fold), and only a small fraction of putative binding sites are actually bound by the MSL complex. The dosage-compensation machinery shares this characteristic with many other sequence-specific binding factors whose predicted target motifs are often in vast excess to the sites actually utilized. It has been speculated that other genomic aspects, such as chromatin context or the 3D organization of the genome, could help to distinguish between utilized and nonutilized copies of a motif. The finding that a large number of sites can acquire the ability to recruit the MSL complex, without any apparent associated changes at the DNA level, supports the view that epigenetic modifications or changes to the 3D architecture of the genome help to ultimately determine which putative binding sites in the genome are actually utilized. In D. melanogaster, the X chromosome has a unique satellite DNA composition, and it was suggested that these repeats play a primary role in determining X identity during dosage compensation. Furthermore, localization of the MSL complex to MREs is dependent on an additional cofactor, the CLAMP protein. CLAMP binds directly to GA-rich MRE sequences and targets MSL to the X chromosome but also binds to GA-rich sequence elements throughout the genome. Recent work has shown that variability in sequence composition within similar GA-rich motifs drive specificity for CLAMP binding, and variation within seemingly similar cis elements may also drive context-specific targeting of the MSL complex. Future investigations of changes in the chromatin level, the repeat content, and the genomic architecture of these newly formed sex chromosomes will help to resolve this outstanding question (Ellison, 2019).

    Allelic polymorphism at foxo contributes to local adaptation in Drosophila melanogaster

    The insulin/insulin-like growth factor signaling pathway has been hypothesized as a major determinant of life-history profiles that vary adaptively in natural populations. In Drosophila melanogaster, multiple components of this pathway vary predictably with latitude; this includes foxo, a conserved gene that regulates insulin signaling and has pleiotropic effects on a variety of fitness-associated traits. It was hypothesized that allelic variation at foxo contributes to genetic variance for size-related traits that vary adaptively with latitude. Patterns of variation were examined among natural populations along a latitudinal transect in the eastern United States; thorax length, wing area, wing loading, and starvation tolerance were found to exhibit significant latitudinal clines for both males and females but that development time does not vary predictably with latitude. Recombinant outbred populations were generated, naturally occurring allelic variation at foxo, which exhibits stronger clinality than expected, were shown to be associated with the same traits that vary with latitude in the natural populations. These results suggest that allelic variation at foxo contributes to adaptive patterns of life-history variation in natural populations of this genetic model (Betancourt, 2021).

    Gene regulatory evolution in cold-adapted fly populations neutralizes plasticity and may undermine genetic canalization

    The relationships between adaptive evolution, phenotypic plasticity, and canalization remain incompletely understood. Theoretical and empirical studies have made conflicting arguments on whether adaptive evolution may enhance or oppose the plastic response. Gene regulatory traits offer excellent potential to study the relationship between plasticity and adaptation, and they can now be studied at the transcriptomic level. This study took advantage of three closely-related pairs of natural populations of Drosophila melanogaster from contrasting thermal environments that reflect three separate instances of cold tolerance evolution. The transcriptome-wide plasticity in gene expression levels and alternative splicing (intron usage) were measured between warm and cold laboratory environments. Suspected adaptive changes in both gene expression and alternative splicing tended to neutralize the ancestral plastic response. Further, the hypothesis was tested that adaptive evolution can lead to decanalization of selected gene regulatory traits. Strong evidence was found that suspected adaptive gene expression (but not splicing) changes in cold-adapted populations are more vulnerable to the genetic perturbation of inbreeding than putatively neutral changes. Some evidence was found that these patterns may reflect a loss of genetic canalization accompanying adaptation, although other processes including hitchhiking recessive deleterious variants may contribute as well. These findings augment our understanding of genetic and environmental effects on gene regulation in the context of adaptive evolution (Huang, 2022).

    Metabolic and immunological responses of Drosophila melanogaster to dietary restriction and bacterial infection differ substantially between genotypes in a population

    To respond to changing environmental conditions, a population may either shift toward better-adapted genotypes or adapt on an individual level. The present work aimed to quantify the relevance of these two processes by comparing the responses of defined Drosophila melanogaster populations to different stressors. To do this, two homogeneous populations (isofemale lines), which differ significantly in fitness, and a synthetic heterogeneous population were infected with a specific pathogen and/or exposed to food restriction. Pectobacterium carotovorum was used to infect Drosophila larvae either fed standard or protein-restricted diet. In particular, the two homogeneous groups, which diverged in their fitness, showed considerable differences in all parameters assessed (survivorship, protein and lipid contents, Phenol oxidase (PO) activity, and antibacterial rate). Under fully nutritious conditions, larvae of the homogeneous population with low fitness exhibited lower survivorship and protein levels, as well as higher PO activity and antibacterial rate compared with the fitter population. A protein-restricted diet and bacterial infection provoked a decrease in survivorship, and antibacterial rate in most populations. Bacterial infection elicited an opposite response in protein and lipid content in both isofemale lines tested. Interestingly, the heterogeneous population showed a complex response pattern. The response of the heterogeneous population followed the fit genotype in terms of survival and antibacterial activity but followed the unfit genotype in terms of PO activity. In conclusion, these results show that defined genotypes exhibit highly divergent responses to varying stressors that are difficult to predict. Furthermore, the responses of heterogeneous populations do not follow a fixed pattern showing a very high degree of plasticity and differences between different genotypes (Meshrif, 2022).

    Evolution of a fatty acyl-CoA elongase underlies desert adaptation in Drosophila

    Traits that allow species to survive in extreme environments such as hot-arid deserts have independently evolved in multiple taxa. However, the genetic and evolutionary mechanisms underlying these traits have thus far not been elucidated. This study shows that Drosophila mojavensis, a desert-adapted fruit fly species, has evolved high desiccation resistance by producing long-chain methyl-branched cuticular hydrocarbons (mbCHCs) that contribute to a cuticular lipid layer reducing water loss. The ability to synthesize these longer mbCHCs is due to evolutionary changes in a fatty acyl-CoA elongase (mElo). mElo knockout in D. mojavensis led to loss of longer mbCHCs and reduction of desiccation resistance at high temperatures but did not affect mortality at either high temperatures or desiccating conditions individually. Phylogenetic analysis showed that mElo is a Drosophila-specific gene, suggesting that while the physiological mechanisms underlying desert adaptation may be similar between species, the genes involved in these mechanisms may be species or lineage specific (Wang, 2023).

    Gene expression clines reveal local adaptation and associated trade-offs at a continental scale

    Local adaptation, where fitness in one environment comes at a cost in another, should lead to spatial variation in trade-offs between life history traits and may be critical for population persistence. Recent studies have sought genomic signals of local adaptation, but often have been limited to laboratory populations representing two environmentally different locations of a species' distribution. This study measured gene expression, as a proxy for fitness, in males of Drosophila subobscura, occupying a 20 degrees latitudinal and 11 ° C thermal range. Uniquely, six populations were sampled, and both common garden and semi-natural responses to identify signals of local adaptation were identified. Contrasting patterns of investment were found: transcripts with expression positively correlated to latitude were enriched for metabolic processes, expressed across all tissues whereas negatively correlated transcripts were enriched for reproductive processes, expressed primarily in testes. When using only the end populations, to compare the results to previous studies, it was found that locally adaptive patterns were obscured. While phenotypic trade-offs between metabolic and reproductive functions across widespread species are well-known, the results identify underlying genetic and tissue responses at a continental scale that may be responsible for this. This may contribute to understanding population persistence under environmental change (Porcelli, 2016).

    Experimental evolution of gene expression and plasticity in alternative selective regimes

    Little is known of how gene expression and its plasticity evolves as populations adapt to different environmental regimes. Expression is expected to evolve adaptively in all populations but only those populations experiencing environmental heterogeneity are expected to show adaptive evolution of plasticity. This study measured the transcriptome in a cadmium-enriched diet and a salt-enriched diet for experimental populations of Drosophila melanogaster that evolved for ~130 generations in one of four selective regimes: two constant regimes maintained in either cadmium or salt diets and two heterogeneous regimes that varied either temporally or spatially between the two diets. For populations evolving in constant regimes, a strong signature of counter-gradient evolution was found; the evolved expression differences between populations adapted to alternative diets is opposite to the plastic response of the ancestral population that is naive to both diets. Based on expression patterns in the ancestral populations, a set of genes was identified for which selection in heterogeneous regimes was predicted to result in increases in plasticity, and the expected pattern was found. In contrast, a set of genes where reduced plasticity was predicted did not follow expectation. Nonetheless, both gene sets showed a pattern consistent with adaptive expression evolution in heterogeneous regimes, highlighting the difference between observing 'optimal' plasticity and improvements in environment-specific expression. Looking across all genes, there is evidence in all regimes of differences in biased allele expression across environments ('allelic plasticity') and this is more common among genes with plasticity in total expression (Huang, 2016).

    Reasons for success: rapid evolution for desiccation resistance and life-history changes in the polyphagous fly Anastrepha ludens

    Species that exhibit broad ranges of distribution may successfully navigate environmental changes by modifying some of their life history traits. Environmental humidity imposes a critical stress that organisms may overcome by increasing their resistance to desiccation. This study used experimental evolution to investigate adaptation to desiccation in the tephritid Anastrepha ludens, a species with high fecundity, late maturation and long lifespan. This study measured morphological, physiological, developmental as well as demographic changes involved in the adaptation to desiccation. Notwithstanding a low heritability (h2 = 0.237), desiccation resistance evolved extremely rapidly and few negative trade-offs were detected. Selected flies exhibited correlated increases in longevity, body size, the amount of body lipids and bulk water content, and in the duration of the pupal stage. Females further delayed sexual maturation, decreased daily fecundity but retained high lifetime reproductive potential. No differences in male mating competitiveness were found. Selected and control lines differed in longevity but not in total female fecundity, demonstrating that A. ludens flies have the capability for fast adaptation to desiccation without loosing their reproductive capability. Thus, it seems that a rapid evolutionary response to desiccation in this polyphagous insect works as a buffer for environmental variation and reduces the strength of selection on reproductive traits (Tejeda, 2016).

    Cold adaptation increases rates of nutrient flow and metabolic plasticity during cold exposure in Drosophila melanogaster

    Metabolic flexibility is an important component of adaptation to stressful environments, including thermal stress and latitudinal adaptation. The direct relationship between selection on thermal stress hardiness and metabolic flux has not previously been tested. This study investigated flexibility of nutrient catabolism during cold stress in Drosophila artificially selected for fast or slow recovery from chill coma (i.e. cold-hardy or -susceptible), specifically testing the hypothesis that stress adaptation increases metabolic turnover. Using 13C-labelled glucose, this study first showed that cold-hardy flies more rapidly incorporate ingested carbon into amino acids and newly synthesized glucose, permitting rapid synthesis of proline, a compound shown elsewhere to improve survival of cold stress. Second, using glucose and leucine tracers cold-hardy flies were shown to have higher oxidation rates than cold-susceptible flies before cold exposure, similar oxidation rates during cold exposure, and returned to higher oxidation rates during recovery. Additionally, cold-hardy flies transferred compounds among body pools more rapidly during cold exposure and recovery. Increased metabolic turnover may allow cold-adapted flies to better prepare for, resist and repair/tolerate cold damage. This work illustrates for the first time differences in nutrient fluxes associated with cold adaptation, suggesting that metabolic costs associated with cold hardiness could invoke resource-based trade-offs that shape life histories (Williams, 2016).

    Colder environments did not select for a faster metabolism during experimental evolution of Drosophila melanogaster

    The effect of temperature on the evolution of metabolism has been the subject of debate for a century; however, no consistent patterns have emerged from comparisons of metabolic rate within and among species living at different temperatures. This study used experimental evolution to determine how metabolism evolves in populations of Drosophila melanogaster exposed to one of three selective treatments: a constant 16 ° C, a constant 25 ° C, or temporal fluctuations between 16 and 25 ° C. August Krogh's controversial hypothesis was tested that colder environments select for a faster metabolism. Given that colder environments also experience greater seasonality, the hypothesis was also tested that temporal variation in temperature may be the factor that selects for a faster metabolism. The metabolic rate of flies from each selective treatment was measured at 16, 20.5, and 25 ° C. Although metabolism was faster at higher temperatures, flies from the selective treatments had similar metabolic rates at each measurement temperature. Based on variation among genotypes within populations, heritable variation in metabolism was likely sufficient for adaptation to occur. It is concluded that colder or seasonal environments do not necessarily select for a faster metabolism. Rather, other factors besides temperature likely contribute to patterns of metabolic rate over thermal clines in nature (Alton, 2016).

    Adaptive patterns of phenotypic plasticity in laboratory and field environments in Drosophila melanogaster

    Identifying mechanisms of adaptation to variable environments is essential in developing a comprehensive understanding of evolutionary dynamics in natural populations. Phenotypic plasticity allows for phenotypic change in response to changes in the environment, and as such may play a major role in adaptation to environmental heterogeneity. This study examined the plasticity of stress response in D. melanogaster originating from two distinct geographic regions and ecological habitats. Adults were given a short-term, 5-day exposure to combinations of temperature and photoperiod to elicit a plastic response for three fundamental aspects of stress tolerance that vary adaptively with geography. This was replicated in both the laboratory and in outdoor enclosures in the field. In the laboratory, geographic origin was found to be the primary determinant of the stress response. Temperature and the interaction between temperature and photoperiod were also found to significantly affect stress resistance. In the outdoor enclosures, plasticity was distinct among traits and between geographic regions. These results demonstrate that short-term exposure of adults to ecologically relevant environmental cues results in predictable effects on multiple aspects of fitness. These patterns of plasticity vary among traits and are highly distinct between the two examined geographic regions, consistent with patterns of local adaptation to climate and associated environmental parameters (Mathur, 2016).

    Genomic trajectories to desiccation resistance: Convergence and divergence among replicate selected Drosophila lines

    Adaptation to environmental stress is critical for long-term species persistence. With climate change and other anthropogenic stressors compounding natural selective pressures, understanding the nature of adaptation is as important as ever in evolutionary biology. This study investigated this issue in a set of replicated Drosophila lines selected for increased desiccation resistance, a classical physiological trait that has been closely linked to Drosophila species distributions. Pooled whole-genome sequencing was used to compare the genetic basis of their selection responses. While selected SNPs in replicates of the same treatment (desiccation-selection or lab adaptation) tended to change frequency in the same direction, suggesting some commonality in the selection response, candidate SNP and gene lists often differed among replicates. Three of the five desiccation-selection replicates showed significant overlap at the gene and network level. All five replicates showed enrichment for ovary-expressed genes, suggesting maternal effects on the selected trait. Divergence between pairs of replicate lines for desiccation-candidate SNPs was greater than between pairs of control lines. This difference also far exceeded the divergence between pairs of replicate lines for neutral SNPs. Overall, while there was overlap in the direction of allele frequency changes and the network and functional categories affected by desiccation selection, replicates showed unique responses at all levels likely reflecting hitchhiking effects, and highlighting the challenges in identifying candidate genes from these types of experiments when traits are likely to be polygenic (Griffin, 2016).

    Independent natural genetic variation of punishment- versus relief-memory

    A painful event establishes two opponent memories: cues that are associated with pain onset are remembered negatively, whereas cues that coincide with the relief at pain offset acquire positive valence. Such punishment- versus relief-memories are conserved across species, including humans, and the balance between them is critical for adaptive behaviour with respect to pain and trauma. In the fruit fly, Drosophila melanogaster as a study case, this study found that both punishment- and relief-memories display natural variation across wild-derived inbred strains, but they do not covary, suggesting a considerable level of dissociation in their genetic effectors. This provokes the question whether there may be heritable inter-individual differences in the balance between these opponent memories in man, with potential psycho-clinical implications (Appel, 2016).

    The genetic basis of natural variation in Drosophila (Diptera: Drosophilidae) virgin egg retention

    Drosophila melanogaster is able to thrive in harsh northern climates through adaptations in life-history traits and physiological mechanisms that allow for survival through the winter. This examined the genetic basis of natural variation in one such trait, female virgin egg retention, which was previously shown to vary clinally and seasonally. To further understanding of the genetic basis and evolution of virgin egg retention, a genome-wide association study (GWAS) was performed using the previously sequenced Drosophila Genetic Reference Panel (DGRP) mapping population. Twenty-nine single nucleotide polymorphisms (SNPs) associated with virgin egg retention were found, and six available mutant lines, each harboring a mutation in a candidate gene, were examined for effects on egg retention time. Four out of the six mutant lines had defects in egg retention time as compared with the respective controls: mun, T48, Mes-4, and Klp67A Surprisingly, none of these genes has a recognized role in ovulation control, but three of the four genes have known effects on fertility or have high expression in the ovaries. The SNP set associated with egg retention time was enriched for clinal SNPs. The majority of clinal SNPs had alleles associated with longer egg retention present at higher frequencies in higher latitudes. These results support previous studies that show higher frequency of long retention times at higher latitude, providing evidence for the adaptive value of virgin egg-retention (Akhund-Zade, 2016).

    Testing for local adaptation and evolutionary potential along altitudinal gradients in rainforest Drosophila: beyond laboratory estimates

    Predicting how species will respond to the rapid climatic changes predicted this century is an urgent task. Species distribution models (SDMs) use the current relationship between environmental variation and species' abundances to predict the effect of future environmental change on their distributions. However, two common assumptions of SDMs are likely to be violated in many cases: (i) that the relationship of environment with abundance or fitness is constant throughout a species' range and will remain so in future and (ii) that abiotic factors (e.g. temperature, humidity) determine species' distributions. These assumptions were tested by relating field abundance of the rainforest fruit fly Drosophila birchii to ecological change across gradients that include its low and high altitudinal limits. Then, how such ecological variation affects the fitness of 35 D. birchii families transplanted in 591 cages to sites along two altitudinal gradients, was tested to determine whether genetic variation in fitness responses could facilitate future adaptation to environmental change. Overall, field abundance was highest at cooler, high-altitude sites, and declined towards warmer, low-altitude sites. By contrast, cage fitness (productivity) increased towards warmer, lower-altitude sites, suggesting that biotic interactions (absent from cages) drive ecological limits at warmer margins. In addition, the relationship between environmental variation and abundance varied significantly among gradients, indicating divergence in ecological niche across the species' range. However, there was no evidence for local adaptation within gradients, despite greater productivity of high-altitude than low-altitude populations when families were reared under laboratory conditions. Families also responded similarly to transplantation along gradients, providing no evidence for fitness trade-offs that would favour local adaptation. These findings highlight the importance of (i) measuring genetic variation in key traits under ecologically relevant conditions, and (ii) considering the effect of biotic interactions when predicting species' responses to environmental change (O'Brien, 2017)

    Genomics of parallel experimental evolution in Drosophila

    What are the genomic foundations of adaptation in sexual populations? This question was addressed using fitness-character and whole-genome sequence data from 30 Drosophila laboratory populations. These 30 populations are part of a nearly forty-year laboratory radiation featuring three selection regimes, each shared by ten populations for up to 837 generations, with moderately large effective population sizes. Each of three sets of ten populations that shared a selection regime consist of five populations that have long been maintained under that selection regime, paired with five populations that had only recently been subjected to that selection regime. A high degree of evolutionary parallelism in fitness phenotypes was found when most-recent selection regimes are shared, as in previous studies from this laboratory. Genomic parallelism was also found with respect to the frequencies of single-nucleotide polymorphisms, transposable elements, insertions, and structural variants, which was expected. Entirely unexpected was a high degree of parallelism for linkage disequilibrium. The evolutionary genetic changes among these sexual populations are rapid and genomically extensive. This pattern may be due to segregating functional genetic variation that is abundantly maintained genome-wide by selection, variation that responds immediately to changes of selection regime (Graves, 2017).

    Geographical analysis of diapause inducibility in European Drosophila melanogaster populations

    Seasonal overwintering in insects represents an adaptation to stressful environments and in European Drosophila melanogaster females, low temperatures and short photoperiods can induce an ovarian diapause. Diapause may represent a recent (<15Ky) adaptation to the colonisation of temperate Europe by D. melanogaster from tropical sub-Saharan Africa, because African D. melanogaster and the sibling species D. simulans, have been reported to fail to undergo diapause. Over the past few centuries, D. melanogaster have also invaded North America and Australia, and eastern populations on both continents show a predictable latitudinal cline in diapause induction. In Europe however, a new diapause-enhancing timeless allele, ls-tim, is observed at high levels in southern Italy ( approximately 80%), where it appears to have arisen and has spread throughout the continent with a frequency of approximately 20% in Scandinavia. Given the phenotype of ls-tim and its geographical distribution, it was predicted that it would work against any latitudinal cline in diapause induction within Europe. Indeed this study revealed that any latitudinal cline for diapause in Europe is very weak, as predicted by ls-tim frequencies. In contrast, ls-tim frequencies were determined in North America and it was observed that they would be expected to strengthen the latitudinal pattern of diapause. The results reveal how a newly arisen mutation, can, via the stochastic nature of where it initially arose, blur an otherwise adaptive geographical pattern (Pegoraro, 2017)

    Evolution of circadian rhythms in Drosophila melanogaster populations reared in constant light and dark regimes for over 330 generations

    Organisms are believed to have evolved circadian clocks as adaptations to deal with cyclic environmental changes, and therefore it has been hypothesized that evolution in constant environments would lead to regression of such clocks. This study examined whether circadian clocks and the associated properties evolve differently under constant light and constant darkness. Activity-rest, adult emergence and oviposition rhythms were measured of D. melanogaster populations that have been maintained for over 19 years (~330 generations) under three different light regimes - constant light (LL), light-dark cycles of 12:12 h (LD) and constant darkness (DD). While circadian rhythms in all the three behaviors persist in both LL and DD stocks with no differences in circadian period, they differed in certain aspects of the entrained rhythms when compared to controls reared in rhythmic environment (LD). Interestingly, it was also observed that DD stocks have evolved significantly higher robustness or power of free-running activity-rest and adult emergence rhythms compared to LL stocks. Thus, this study, in addition to corroborating previous results of circadian clock evolution in constant light, also highlights that, contrary to the expected regression of circadian clocks, rearing in constant darkness leads to the evolution of more robust circadian clocks which may be attributed to an intrinsic adaptive advantage of circadian clocks and/or pleiotropic functions of clock genes in other traits (Shindey, 2017).

    Transcriptional polymorphism of piRNA regulatory genes underlies the mariner activity in D. simulans testes

    During colonization of new areas, natural populations have to deal with changing environments, and transposable elements (TEs) can be useful "tools" in the adaptation process since they are major contributor to the structural and functional evolution of genomes. In this general context, the activity (copy number, transcriptional and excision rate) of the mariner mos1 element was estimated in 19 natural populations of D. simulans. It is shown (1) that mos1 expression is always higher and more variable in testes than in ovaries; (2) that mos1 activity is higher in colonizing populations compared to the sub-Saharan African ones (ancestral populations); (3) that mos1 variations in transcript levels and copy number are negatively correlated to transcriptional variations of piRNA genes, aubergine and argonaute3. Furthermore, mos1 levels of expression in testes highly contrast with the low expression patterns of ago3. These results strongly suggest that the expression polymorphism of piRNA genes could be responsible for the mos1 variations, first between male and female germlines and second, according to the status of natural populations (colonizing or not). These results provide new perspectives about TEs and piRNA genes co-evolution in Drosophila germlines (Saint-Leandre, 2017).

    A test for gene flow among sympatric and allopatric Hawaiian picture-winged Drosophila

    The Hawaiian Drosophila are one of the most species-rich endemic groups in Hawaii and a spectacular example of adaptive radiation. Drosophila silvestris and D. heteroneura are two closely related picture-winged Drosophila species that occur sympatrically on Hawaii Island and are known to hybridize in nature, yet exhibit highly divergent behavioral and morphological traits driven largely through sexual selection. Their closest-related allopatric species, D. planitibia from Maui, exhibits hybrid male sterility and reduced behavioral reproductive isolation when crossed experimentally with D. silvestris or D. heteroneura. A modified four-taxon test for gene flow was applied to recently obtained genomes of the three Hawaiian Drosophila species. The analysis indicates recent gene flow in sympatry, but also, although less extensive, between allopatric species. This study underscores the prevalence of gene flow, even in taxonomic groups considered classic examples of allopatric speciation on islands. The potential confounding effects of gene flow in phylogenetic and population genetics inference are discussed, as well as the implications for conservation (Kang, 2017).

    Experimental test and refutation of a classic case of molecular adaptation in Drosophila melanogaster

    Identifying the genetic basis for adaptive differences between species requires explicit tests of historical hypotheses concerning the effects of past changes in gene sequence on molecular function, organismal phenotype and fitness. This challenge was addressed by combining ancestral protein reconstruction with biochemical experiments and physiological analysis of transgenic animals that carry ancestral genes. A widely held hypothesis of molecular adaptation was tested in this study-that changes in the alcohol dehydrogenase protein (ADH) along the lineage leading to Drosophila melanogaster increased the catalytic activity of the enzyme and thereby contributed to the ethanol tolerance and adaptation of the species to its ethanol-rich ecological niche. These experiments strongly refute the predictions of the adaptive ADH hypothesis and caution against accepting intuitively appealing accounts of historical molecular adaptation that are based on correlative evidence. The experimental strategy employed can be used to decisively test other adaptive hypotheses and the claims they entail about past biological causality (Siddiq, 2017).

    Adaptive evolution of gene expression in Drosophila

    Gene expression levels are important quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies have revealed substantial adaptive evolution at the genomic level, but the evolutionary modes of gene expression remain controversial. This study presents evidence that adaptation dominates the evolution of gene expression levels in flies. 64% of the observed expression divergence across seven Drosophila species are adaptive changes driven by directional selection. The results are derived from time-resolved data of gene expression divergence across a family of related species, using a probabilistic inference method for gene-specific selection. Adaptive gene expression is stronger in specific functional classes, including regulation, sensory perception, sexual behavior, and morphology. Moreover, a large group of genes was identifed with sex-specific adaptation of expression, which predominantly occurs in males. This analysis opens an avenue to map system-wide selection on molecular quantitative traits independently of their genetic basis (Nourmohammad, 2017).

    Adaptive evolution of gene expression in Drosophila

    Gene expression levels are important quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies have revealed substantial adaptive evolution at the genomic level, but the evolutionary modes of gene expression remain controversial. This study presents evidence that adaptation dominates the evolution of gene expression levels in flies. 64% of the observed expression divergence across seven Drosophila species are adaptive changes driven by directional selection. The results are derived from time-resolved data of gene expression divergence across a family of related species, using a probabilistic inference method for gene-specific selection. Adaptive gene expression is stronger in specific functional classes, including regulation, sensory perception, sexual behavior, and morphology. Moreover, a large group of genes was identified with sex-specific adaptation of expression, which predominantly occurs in males. This analysis opens an avenue to map system-wide selection on molecular quantitative traits independently of their genetic basis (Nourmohammad, 2017).

    The inference of adaptation exploits the complex dependence of the expression divergence on the evolutionary distance between species. It reflects two fundamental evolutionary features of quantitative traits. First, such traits generate a divergence pattern with two distinct molecular clocks: at a short evolutionary distance, the divergence is always near the expected value under neutrality; at a longer distance, it depends jointly on stabilizing and directional selection. This feature reconciles seemingly contradictory results of previous studies: analysis of closely related species produces a signal of neutral evolution, whereas evolutionary constraint becomes apparent for more distant species. Second, the phenotypic evolution of gene expression decouples from details of its genetic basis. This explains why overall strong selection on gene expression levels was found even though selection on individual QTLs is often weak. The probabilistic extension of the curren inference scheme, which is based on gene-specific expression divergence, identifies functional gene classes associated with adaptive evolution of regulation (Nourmohammad, 2017).

    The selection model underlying this analysis is a single-peak fitness seascape, which contains components of stabilizing and directional selection on a quantitative trait. These components are well-established notions of quantitative genetics on micro-evolutionary timescales. Each of them can provide a snapshot of the predominant selection pressure in a population. However, the description of selection remains incomplete as a description of selection over macro-evolutionary periods. If selection on a trait is directional at a given evolutionary time, will that selection relax after the trait value has significantly adapted in the direction of selection? If selection is stabilizing, can it be assumed that the optimal trait value will remain invariant in the context of a different species? To address these questions, a conceptual and quantitative synthesis of stabilizing and directional selection is need. The single-peak seascape model arguably provides the simplest such synthesis. It also provides a simple picture of continual adaptation over macro-evolutionary periods: a species follows a moving fitness peak, and this process generates positive fitness flux but no net increase in fitness (Nourmohammad, 2017).

    This method of selection inference can be applied to a spectrum of molecular quantitative traits with a complex genetic basis, provided that comparative data from multiple, sufficiently diverged species are available. Such traits include genome-wide protein levels, protein-DNA binding interactions, and enzymatic activities. For most of these traits, only partial knowledge is available of the underlying genetic loci and their effects on trait and fitness. This method complements QTL studies and opens a way to infer quantitative phenotype-fitness maps at the systems level (Nourmohammad, 2017).

    Inter- and intra-specific genomic divergence in Drosophila montana shows evidence for cold adaptation

    The genomes of species that are ecological specialists will likely contain signatures of genomic adaptation to their niche. This study describes the genome of Drosophila montana, which is the most extremely cold-adapted Drosophila species. Branch tests were used to identify genes showing accelerated divergence in contrasts between cold- and warm adapted species, and about 250 genes were identified that show differences, possibly driven by a lower synonymous substitution rate in cold-adapted species. Evidence was sought of accelerated divergence between D. montana and D. virilis, a previously sequenced relative, and no strong evidence was found for divergent selection on coding sequence variation. Divergent genes are involved in a variety of functions, including cuticular and olfactory processes. Three populations of D. montana were resequenced from its ecological and geographic range. Outlier loci were more likely to be found on the X chromosome and there was a greater than expected overlap between population outliers and those genes implicated in cold adaptation between Drosophila species, implying some continuity of selective process at these different evolutionary scales (Parker, 2018).

    Effects of evolutionary history on genome wide and phenotypic convergence in Drosophila populations

    Studies combining experimental evolution and next-generation sequencing have found that adaptation in sexually reproducing populations is primarily fueled by standing genetic variation. Consequently, the response to selection is rapid and highly repeatable across replicate populations. Some studies suggest that the response to selection is highly repeatable at both the phenotypic and genomic levels, and that evolutionary history has little impact. Other studies suggest that even when the response to selection is repeatable phenotypically, evolutionary history can have significant impacts at the genomic level. This study tests two hypotheses that may explain this discrepancy. Hypothesis 1: Past intense selection reduces evolutionary repeatability at the genomic and phenotypic levels when conditions change. Hypothesis 2: Previous intense selection does not reduce evolutionary repeatability, but other evolutionary mechanisms may. These hypotheses were tested using D. melanogaster populations that were subjected to 260 generations of intense selection for desiccation resistance and have since been under relaxed selection for the past 230 generations. It was found that, with the exception of longevity and to a lesser extent fecundity, 230 generations of relaxed selection has erased the extreme phenotypic differentiation previously found. No signs were found of genetic fixation, and only limited evidence of genetic differentiation between previously desiccation resistance selected populations and their controls. These findings suggest that evolution in this system is highly repeatable even when populations have been previously subjected to bouts of extreme selection. It is therefore concluded that evolutionary repeatability can overcome past bouts of extreme selection in Drosophila experimental evolution, provided experiments are sufficiently long and populations are not inbred (Phillips, 2018).

    Positive selection at sites of chemosensory genes is associated with the recent divergence and local ecological adaptation in cactophilic Drosophila

    Adaptation to new hosts in phytophagous insects often involves mechanisms of host recognition by genes of sensory pathways. Most often the molecular evolution of sensory genes has been explained in the context of the birth-and-death model. The role of positive selection is less understood, especially associated with host adaptation and specialization. This study aimed to contribute evidence for this latter hypothesis by considering the case of Drosophila mojavensis, a species with an evolutionary history shaped by multiple host shifts in a relatively short time scale, and its generalist sister species, D. arizonae. A phylogenetic and population genetic analysis framework was used to test for positive selection in a subset of four chemoreceptor genes, one gustatory receptor (Gr) and three odorant receptors (Or), for which their expression has been previously associated with host shifts. Strong evidence was found of positive selection at several amino acid sites in all genes investigated, most of which exhibited changes predicted to cause functional effects in these transmembrane proteins. A significant portion of the sites identified as evolving positively were largely found in the cytoplasmic region, although a few were also present in the extracellular domains. The pattern of substitution observed suggests that some of these changes likely had an effect on signal transduction as well as odorant recognition and protein-protein interactions. These findings support the role of positive selection in shaping the pattern of variation at chemosensory receptors, both during the specialization onto one or a few related hosts, but as well as during the evolution and adaptation of generalist species into utilizing several hosts (Dizz, 2018).

    Ultrastructural variation and adaptive evolution of the ovipositor in the endemic Hawaiian Drosophilidae

    Ecological diversification of the endemic Hawaiian Drosophilidae has been accompanied by striking divergence in egg morphology, and ovarian structure and function. To determine how these flies successfully oviposit in a variety of breeding substrates, Scanning Electron Microscopy was used to examine the ultrastructure of the ovipositor of a sample of 65 Drosophila species and five Scaptomyza species of this hyperdiverse monophyletic group. The Drosophila species analyzed included representatives of the fungus-breeding haleakalae group, the leaf-breeding antopocerus and modified tarsus groups, the modified mouthparts species group, the nudidrosophila, and the picture wing clade; the latter sample of 41 species from four species groups included stem- and bark-breeders, as well as tree sap flux-breeders. Ovipositor length was found to vary more than 12-fold among Hawaiian drosophilids, with the longest ovipositors observed in the bark-breeding species and the shortest among the Scaptomyza and fungus-breeders. More noteworthy is the striking variation in overall shape and proportions of the ovipositor, in the shape of the apical region, and in the pattern of sensory structures or ovisensilla. Ultrastructural observations of the pair of long subapical sensilla on the ventral side identify these as taste bristles. Ovipositor form correlates strongly with the oviposition substrate used by the species, being of a distinctive shape and size in each case. It is inferred that the observed morphological divergence in the ovipositor is adaptive and the product of natural selection for successful reproduction in alternate microhabitats (Craddock, 2018).

    Genomic changes associated with adaptation to arid environments in cactophilic Drosophila species

    Insights into the genetic capacities of species to adapt to future climate change can be gained by using comparative genomic and transcriptomic data to reconstruct the genetic changes associated with such adaptations in the past. This study investigated the genetic changes associated with adaptation to arid environments, specifically climatic extremes and new cactus hosts, through such an analysis of five repleta group Drosophila species. Disproportionately high rates of gene gains were found in internal branches in the species' phylogeny where cactus use and subsequently cactus specialisation and high heat and desiccation tolerance evolved. The terminal branch leading to the most heat and desiccation resistant species, Drosophila aldrichi, also shows disproportionately high rates of both gene gains and positive selection. Several Gene Ontology terms related to metabolism were enriched in gene gain events in lineages where cactus use was evolving, while some regulatory and developmental genes were strongly selected in the Drosophila aldrichi branch. Transcriptomic analysis of flies subjected to sublethal heat shocks showed many more downregulation responses to the stress in a heat sensitive versus heat resistant species, confirming the existence of widespread regulatory as well as structural changes in the species' differing adaptations. Gene Ontology terms related to metabolism were enriched in the differentially expressed genes in the resistant species while terms related to stress response were over-represented in the sensitive one. It is concluded that daptations to new cactus hosts and hot desiccating environments were associated with periods of accelerated evolutionary change in diverse biochemistries. The hundreds of genes involved suggest adaptations of this sort would be difficult to achieve in the timeframes projected for anthropogenic climate change (Rane, 2019).

    Phenotypic plasticity facilitates initial colonization of a novel environment

    Phenotypic plasticity can allow organisms to respond to environmental changes by producing better matching phenotypes without any genetic change. Because of this, plasticity is predicted to be a major mechanism by which a population can survive the initial stage of colonizing a novel environment. This prediction was tested by challenging wild Drosophila melanogaster with increasingly extreme larval environments and then examining expression of alcohol dehydrogenase (ADH) and its relationship to larval survival in the first generation of encountering a novel environment. Most families responded in the adaptive direction of increased ADH activity in higher alcohol environments and families with higher plasticity were also more likely to survive in the highest alcohol environment. Thus, plasticity of ADH activity was positively selected in the most extreme environment and was a key trait influencing fitness. Furthermore, there was significant heritability of ADH plasticity that can allow plasticity to evolve in subsequent generations after initial colonization. The adaptive value of plasticity, however, was only evident in the most extreme environment and had little impact on fitness in less extreme environments. The results provide one of the first direct tests of the adaptive role of phenotypic plasticity in colonizing a novel environment (Wang, 2019).

    Ribosomal DNA Instability as a Potential Cause of Karyotype Evolution

    Karyotype refers to the configuration of the genome into a set of chromosomes. The karyotype difference between species is expected to impede various biological processes, such as chromosome segregation and meiotic chromosome pairing, potentially contributing to incompatibility. Karyotypes can rapidly change between closely related species and even among populations of the same species. However, the forces driving karyotype evolution are poorly understood. This study describes a unique karyotype of a Drosophila melanogaster strain isolated from the Seychelles archipelago. This strain has lost the ribosomal DNA (rDNA) locus on the X chromosome. Because the Y chromosome is the only other rDNA-bearing chromosome, all females carry at least one Y chromosome as the source of rDNA. Interestingly, it was found that the strain also carries a truncated Y chromosome (YS) that is stably maintained in the population despite its inability to support male fertility. Modeling and cytological analysis suggest that the Y chromosome has a larger negative impact on female fitness than the YS chromosome. Moreover, an independent strain was generated that lacks X rDNA and has a karyotype of XXY females and XY males. This strain quickly evolved multiple karyotypes: two new truncated Y chromosomes (similar to YS), as well as two independent X chromosome fusions that contain the Y-derived rDNA fragment, eliminating females' dependence on the Y chromosome. Considering that Robertsonian fusions frequently occur at rDNA loci in humans, it is proposed that rDNA loci instability may be one of driving forces of karyotype evolution (Li, 2022).

    Three recent sex chromosome-to-autosome fusions in a Drosophila virilis strain with high satellite DNA content

    The karyotype, or number and arrangement of chromosomes, has varying levels of stability across both evolution and disease. Karyotype changes often originate from DNA breaks near the centromeres of chromosomes, which generally contain long arrays of tandem repeats or satellite DNA. Drosophila virilis possesses among the highest relative satellite abundances of studied species, with almost half its genome composed of three related 7 bp satellites. This study discovered a strain of D. virilis that is inferred to have recently undergone three independent chromosome fusion events involving the X and Y chromosomes, in addition to one subsequent fission event. This study isolated and characterized the four different karyotypes discovered in this strain which is believed to demonstrate remarkable genome instability. One of the substrains with an X-autosome fusion has a X-to-Y chromosome nondisjunction rate 20x higher than the D. virilis reference strain (21% vs. 1%). Finally, an overall higher rate of DNA breakage was found in the substrain with higher satellite DNA compared to a genetically similar substrain with less satellite DNA. This suggests satellite DNA abundance may play a role in the risk of genome instability. Overall, this study introduces a novel system consisting of a single strain with four different karyotypes, which will be useful for future studies of genome instability, centromere function, and sex chromosome evolution (Flynn, 2023).

    Hybrid Breakdown in Male Reproduction Between Recently-Diverged Drosophila melanogaster Populations Has a Complex and Variable Genetic Architecture

    Secondary contact between formerly isolated populations may result in hybrid breakdown, in which untested allelic combinations in hybrids are maladaptive and limit genetic exchange. Studying early-stage reproductive isolation may yield key insights into the genetic architectures and evolutionary forces underlying the first steps toward speciation. This study leveraged the recent worldwide expansion of Drosophila melanogaster to test for hybrid breakdown between populations that diverged within the last 13,000 years. Clear evidence was found for hybrid breakdown in male reproduction, but not female reproduction or viability, supporting the prediction that hybrid breakdown affects the heterogametic sex first. The frequency of non-reproducing F2 males varied among different crosses involving the same southern African and European populations, as did the qualitative effect of cross direction, implying a genetically variable basis of hybrid breakdown and a role for uniparentally inherited factors. The levels of breakdown observed in F2 males were not recapitulated in backcrossed individuals, consistent with the existence of incompatibilities with at least three partners. Thus, some of the very first steps toward reproductive isolation could involve incompatibilities with complex and variable genetic architectures. Collectively, these findings emphasize this system's potential for future studies on the genetic and organismal basis of early-stage reproductive isolation (Lollar, 2023).

    The effects of inversion polymorphisms on patterns of neutral genetic diversity

    The strong reduction in the frequency of recombination in heterozygotes for an inversion and a standard gene arrangement causes the arrangements to become partially isolated genetically, resulting in sequence divergence between them and changes in the levels of neutral variability at nucleotide sites within each arrangement class. Previous theoretical studies on the effects of on neutral variability have assumed either that the population is panmictic or that it is divided into 2 populations subject to divergent selection. In this study, the theory is extended to a model of an arbitrary number of demes connected by migration, using a finite island model with the inversion present at the same frequency in all demes. Recursion relations for mean pairwise coalescent times are used to obtain simple approximate expressions for diversity and divergence statistics for an inversion polymorphism at equilibrium under recombination and drift, and for the approach to equilibrium following the sweep of an inversion to a stable intermediate frequency. The effects of an inversion polymorphism on patterns of linkage disequilibrium are also examined. The reduction in effective recombination rate caused by population subdivision can have significant effects on these statistics. The theoretical results are discussed in relation to population genomic data on inversion polymorphisms, with an emphasis on Drosophila melanogaster. Methods are proposed for testing whether or not inversions are close to recombination-drift equilibrium, and for estimating the rate of recombinational exchange in heterozygotes for inversions; difficulties involved in estimating the ages of inversions are also discussed (Charlesworth, 2023).

    An Ancestral Balanced Inversion Polymorphism Confers Global Adaptation

    Since the pioneering work of Dobzhansky in the 1930s and 1940s, many chromosomal inversions have been identified, but how they contribute to adaptation remains poorly understood. In Drosophila melanogaster, the widespread inversion polymorphism In(3R)Payne underpins latitudinal clines in fitness traits on multiple continents. This study used single-individual whole-genome sequencing, transcriptomics, and published sequencing data to study the population genomics of this inversion on four continents: in its ancestral African range and in derived populations in Europe, North America, and Australia. The results confirm that this inversion originated in sub-Saharan Africa and subsequently became cosmopolitan; marked monophyletic divergence of inverted and noninverted karyotypes was observed, with some substructure among inverted chromosomes between continents. Despite divergent evolution of this inversion since its out-of-Africa migration, derived non-African populations exhibit similar patterns of long-range linkage disequilibrium between the inversion breakpoints and major peaks of divergence in its center, consistent with balancing selection and suggesting that the inversion harbors alleles that are maintained by selection on several continents. Using RNA-sequencing, this study identified overlap between inversion-linked single-nucleotide polymorphisms and loci that are differentially expressed between inverted and noninverted chromosomes. Expression levels are higher for inverted chromosomes at low temperature, suggesting loss of buffering or compensatory plasticity and consistent with higher inversion frequency in warm climates. These results suggest that this ancestrally tropical balanced polymorphism spread around the world and became latitudinally assorted along similar but independent climatic gradients, always being frequent in subtropical/tropical areas but rare or absent in temperate climates (Kapun, 2023).

    Female meiotic drive shapes the distribution of rare inversion polymorphisms in Drosophila melanogaster

    In all species, new chromosomal inversions are constantly being formed by spontaneous rearrangement and then stochastically eliminated from natural populations. In Drosophila, when new chromosomal inversions overlap with a preexisting inversion in the population, their rate of elimination becomes a function of the relative size, position, and linkage phase of the gene rearrangements. These altered dynamics result from complex meiotic behavior wherein overlapping inversions generate asymmetric dyads that cause both meiotic drive/drag and segmental aneuploidy. In this context, patterns in rare inversion polymorphisms of a natural population can be modeled from the fundamental genetic processes of forming asymmetric dyads via crossing-over in meiosis I and preferential segregation from asymmetric dyads in meiosis II. Here, a mathematical model of crossover-dependent female meiotic drive is developed and parameterized with published experimental data from Drosophila melanogaster laboratory constructs. This mechanism is demonstrated to favor smaller, distal inversions and accelerate the elimination of larger, proximal inversions. Simulated sampling experiments indicate that the paracentric inversions directly observed in natural population surveys of D. melanogaster are a biased subset that both maximizes meiotic drive and minimizes the frequency of lethal zygotes caused by this cytogenetic mechanism. Incorporating this form of selection into a population genetic model accurately predicts the shift in relative size, position, and linkage phase for rare inversions found in this species. The model and analysis presented in this study suggest that this weak form of female meiotic drive is an important process influencing the genomic distribution of rare inversion polymorphisms (Koury, 2023).

    The Adaptive Value of Chromosomal Inversions and Climatic Change-Studies on the Natural Populations of Drosophila subobscura from the Balkans

    The adaptive value of the Drosophila subobscura chromosomal inversion polymorphism with regard to environmental effects is well-known. However, the specific details of the inversion adaptations to the global warming scenario deserve to be analyzed. Toward this aim, polymorphism and karyotypes were studied in 574 individuals from Petnica (Serbia) in annual samples taken in June for the period 2019-2022. Comparing the results of Petnica (Cfa: humid subtropical climate) with those from Avala (Serbia: Cfb, temperate oceanic climate) and Font Groga (Barcelona, Spain; Csa: hot-summer Mediterranean climate), significant differences were observed for their chromosomal polymorphism. In Petnica, inversions from U and E chromosomes mainly reacted significantly with regard to temperature, humidity, and rainfall. Moreover, the inversion polymorphism from Petnica (2019-2022) was compared with that from 1995. In this period, a significant increase in mean and maximum temperature was observed. However, to properly explain the observed variations of inversions over time, it was necessary to carefully analyze annual seasonal changes and particular heat wave episodes. Interestingly, yearly fluctuations of U chromosome 'warm'-adapted inversions corresponded with opposite changes in 'non-thermal' inversions. Perhaps these types of inversions were not correctly defined with regard to thermal adaptation, or these fluctuations were also due to adaptations to other physical and/or biological variables. Finally, a joint study of chromosomal inversion polymorphism from many Balkan populations of D. subobscura indicated that different climatic regions presented distinct composition, including thermal-adapted inversions (Zivanovic, 2023).

    High levels of intra-strain structural variation in Drosophila simulans X pericentric heterochromatin

    Large genome structural variations can impact genome regulation and integrity. Repeat-rich regions like pericentric heterochromatin are vulnerable to structural rearrangements although we know little about how often these rearrangements occur over evolutionary time. Repetitive genome regions are particularly difficult to study with genomic approaches, as they are missing from most genome assemblies. However, cytogenetic approaches offer a direct way to detect large rearrangements involving pericentric heterochromatin. This study used a cytogenetic approach to reveal large structural rearrangements associated with the X pericentromeric region of Drosophila simulans. These rearrangements involve large blocks of satellite DNA-the 500-bp and Rsp-like satellites-which colocalize in the X pericentromeric heterochromatin. This region is polymorphic not only among different strains, but between isolates of the same strain from different labs, and even within individual isolates. On the one hand, these observations raise questions regarding the potential impact of such variation at the phenotypic level and the ability to control for such genetic variability. This highlights the very rapid turnover of the pericentric heterochromatin most likely associated with genomic instability of the X pericentromere. It represents a unique opportunity to study the dynamics of pericentric heterochromatin, the evolution of associated satellites on a very short time scale, and to better understand how structural variation arises (Courret, 2023).

    Genetic redundancy fuels polygenic adaptation in Drosophila

    The genetic architecture of adaptive traits is of key importance to predict evolutionary responses. Most adaptive traits are polygenic-i.e., result from selection on a large number of genetic loci-but most molecularly characterized traits have a simple genetic basis. This discrepancy is best explained by the difficulty in detecting small allele frequency changes (AFCs) across many contributing loci. To resolve this, laboratory natural selection was used to detect signatures for selective sweeps and polygenic adaptation. This study exposed 10 replicates of a Drosophila simulans population to a new temperature regime and uncovered a polygenic architecture of an adaptive trait with high genetic redundancy among beneficial alleles. Convergent responses were observed for several phenotypes-e.g., fitness, metabolic rate, and fat content-and a strong polygenic response (99 selected alleles; mean s = 0.059). However, each of these selected alleles increased in frequency only in a subset of the evolving replicates. Different evolutionary paradigms were discerned based on the heterogeneous genomic patterns among replicates. Redundancy and quantitative trait (QT) paradigms fitted the experimental data better than simulations assuming independent selective sweeps. These results show that natural D. simulans populations harbor a vast reservoir of adaptive variation facilitating rapid evolutionary responses using multiple alternative genetic pathways converging at a new phenotypic optimum. This key property of beneficial alleles requires the modification of testing strategies in natural populations beyond the search for convergence on the molecular level (Barghi, 2019).

    Demographic history of the human commensal Drosophila melanogaster

    The cohabitation of Drosophila melanogaster with humans is nearly ubiquitous. Though it has been well-established that this fly species originated in sub-Saharan Africa, and only recently has spread globally, many details of its swift expansion remain unclear. Elucidating the demographic history of D. melanogaster provides a unique opportunity to investigate how human movement might have impacted patterns of genetic diversity in a commensal species, as well as providing neutral null models for studies aimed at identifying genomic signatures of local adaptation. This study used whole-genome data from five populations (Africa, North America, Europe, Central Asia, and the South Pacific) to carry out demographic inferences, with particular attention to the inclusion of migration and admixture. The importance of these parameters for model fitting is demonstrated, and how previous estimates of divergence times are likely to be significantly underestimated as a result of not including them is shown. Finally, how human movement along early shipping routes might have shaped the present-day population structure of D. melanogaster is discussed (Arguello, 2019).

    A 24 h age difference causes twice as much gene expression divergence as 100 generations of adaptation to a novel environment

    Gene expression profiling is one of the most reliable high-throughput phenotyping methods, allowing researchers to quantify the transcript abundance of expressed genes. Because many biotic and abiotic factors influence gene expression, it is recommended to control them as tightly as possible. This study shows that a 24 h age difference of Drosophila simulans females that were subjected to RNA sequencing (RNA-Seq) five and six days after eclosure resulted in more than 2000 differentially expressed genes. This is twice the number of genes that changed expression during 100 generations of evolution in a novel hot laboratory environment. Importantly, most of the genes differing in expression due to age introduce false positives or negatives if an adaptive gene expression analysis is not controlled for age. These results indicate that tightly controlled experimental conditions, including precise developmental staging, are needed for reliable gene expression analyses, in particular in an evolutionary framework (Hsu, 2019).

    Estimating the timing of multiple admixture pulses during local ancestry inference

    Admixture, the mixing of genetically distinct populations, is increasingly recognized as a fundamental biological process. One major goal of admixture analyses is to estimate the timing of admixture events. Whereas most methods today can only detect the most recent admixture event, this study presents coalescent theory and associated software that can be used to estimate the timing of multiple admixture events in an admixed population. This approach was extensively validated and the conditions under which it can successfully distinguish one from two-pulse admixture models was validated. This approach was applied to real and simulated data of Drosophila melanogaster. Evidence was found of a single very recent pulse of cosmopolitan ancestry contributing to African populations as well as evidence for more ancient admixture among genetically differentiated populations in sub-Saharan Africa. These results suggest this method can quantify complex admixture histories involving genetic material introduced by multiple discrete admixture pulses. The new method facilitates the exploration of admixture and its contribution to adaptation, ecological divergence, and speciation (Medina, 2018).

    The making of a pest: Insights from the evolution of chemosensory receptor families in a pestiferous and invasive fly

    Drosophila suzukii differs from other melanogaster group members in their proclivity for laying eggs in fresh fruit rather than in fermenting fruits. Earlier work has revealed how the olfactory landscape of D. suzukii is dominated by volatiles derived from its unique niche. This study annotated the Olfactory receptors and Gustatory Receptors in D. suzukii and two close relatives, D. biarmipes and D. takahashii, to identify candidate chemoreceptors associated with D. suzukii's unusual niche utilization. A total of 71 Or genes were annotated in D. suzukii, with nine of those being pseudogenes (12.7 %). Alternative splicing of two genes brings the total to 62 genes encoding 66 Ors. Duplications of Or23a and Or67a expanded D. suzukii's Or repertoire, while pseudogenization of Or74a, Or85a, and Or98b reduced the number of functional Ors to roughly the same as other annotated species in the melanogaster group. Seventy-one intact Gr genes and three pseudogenes were annotated in D. suzukii. Alternative splicing in three genes brings the total number of Grs to 81. Signatures of positive selection were identified in two Ors and three Grs at nodes leading to D. suzukii, while three copies in the largest expanded Or lineage, Or67a, also showed signs of positive selection at the external nodes. This analysis of D. suzukii's chemoreceptor repertoires in the context of nine melanogaster group drosophilids, including two of its closest relatives (D. biarmipes and D. takahashii), revealed several candidate receptors associated with the adaptation of D. suzukii to its unique ecological niche (Hickner, 2016).

    Phylogenomic analyses of the genus Drosophila reveals genomic signals of climate adaptation

    Many Drosophila species differ widely in their distributions and climate niches, making them excellent subjects for evolutionary genomic studies. A database was developed of high-quality assemblies for 46 Drosophila species and one closely related Zaprionus. Fifteen of the genomes were newly sequenced, and 20 were improved with additional sequencing. New or improved annotations were generated for all 47 species, assisted by new transcriptomes for 19. Phylogenomic analyses of these data resolved several previously ambiguous relationships, especially in the melanogaster species group. However, it also revealed significant phylogenetic incongruence among genes, mainly in the form of incomplete lineage sorting in the subgenus Sophophora but also including asymmetric introgression in the subgenus Drosophila. Using the phylogeny as a framework and taking into account these incongruences, the data was screened for genome-wide signals of adaptation to different climatic niches. First, phylostratigraphy revealed relatively high rates of recent novel gene gain in three temperate pseudoobscura and five desert-adapted cactophilic mulleri subgroup species. Second, it was found differing ratios of nonsynonymous to synonymous substitutions in several hundred orthologues between climate generalists and specialists, with trends for significantly higher ratios for those in tropical and lower ratios for those in temperate-continental specialists respectively than those in the climate generalists. Finally, resequencing natural populations of 13 species revealed tropics-restricted species generally had smaller population sizes, lower genome diversity and more deleterious mutations than the more widespread species. It is concluded that adaptation to different climates in the genus Drosophila has been associated with large-scale and multifaceted genomic changes (Li, 2022).

    Investigating the phylogenetic history of toxin tolerance in mushroom-feeding Drosophila

    Understanding how and when key novel adaptations evolved is a central goal of evolutionary biology. Within the immigrans-tripunctata radiation of Drosophila, many mushroom-feeding species are tolerant of host toxins, such as cyclopeptides, that are lethal to nearly all other eukaryotes. In this study, phylogenetic and functional approaches were used to investigate the evolution of cyclopeptide tolerance in the immigrans-tripunctata radiation of Drosophila. First, the evolutionary relationships among 48 species in this radiation was inferred using 978 single copy orthologs. These results resolved previous incongruities within species groups across the phylogeny. Second, this study expanded on previous studies of toxin tolerance by assaying 16 of these species for tolerance to α-amanitin and found that six of these species could develop on diet with toxin. Third, fly development was examined on a diet containing a natural mix of toxins extracted from the Death Cap Amanita phalloides mushroom. Both tolerant and susceptible species developed on diet with this mix, though tolerant species survived at significantly higher concentrations. Finally, it was asked how cyclopeptide tolerance might have evolved across the immigrans-tripunctata radiation and inferred that toxin tolerance was ancestral and subsequently lost multiple times. These results suggest the evolutionary history of cyclopeptide tolerance is complex, and simply describing this trait as present or absent does not fully capture the occurrence or impact on this adaptive radiation. More broadly, the evolution of novelty can be more complex than previously thought, and that accurate descriptions of such novelties are critical in studies examining their evolution (Erlenbach, 2023).

    A genome-wide scan for genes under balancing selection in Drosophila melanogaster

    In the history of population genetics balancing selection has been considered as an important evolutionary force, yet until today little is known about its abundance and its effect on patterns of genetic diversity. Several well-known examples of balancing selection have been reported from humans, mice, plants, and parasites. However, only very few systematic studies have been carried out to detect genes under balancing selection. This study carried out a genome scan in Drosophila melanogaster to find signatures of balancing selection in a derived (European) and an ancestral (African) population. A total of 34 genomes were scanned, searching for regions of high genetic diversity and an excess of SNPs with intermediate frequency. In total, 183 candidate genes were found: 141 in the European population and 45 in the African one, with only three genes shared between both populations. Most differences between both populations were observed on the X chromosome, though this might be partly due to false positives. Functionally, an overrepresentation of genes involved in neuronal development and circadian rhythm were found. Furthermore, some of the top genes identified are involved in innate immunity. These results revealed evidence of genes under balancing selection in European and African populations. More candidate genes have been found in the European population. They are involved in several different functions (Croze, 2017).

    Nucleotide diversity inflation as a genome-wide response to experimental lifespan extension in Drosophila melanogaster

    Evolutionary theory predicts that antagonistically selected alleles, such as those with divergent pleiotropic effects in early and late life, may often reach intermediate population frequencies due to balancing selection, an elusive process when sought out empirically. Alternatively, genetic diversity may increase as a result of positive frequency-dependent selection and genetic purging in bottlenecked populations. While experimental evolution systems with directional phenotypic selection typically result in at least local heterozygosity loss, this study reports that selection for increased lifespan in Drosophila melanogaster leads to an extensive genome-wide increase of nucleotide diversity in the selected lines compared to replicate control lines, pronounced in regions with no or low recombination, such as chromosome 4 and centromere neighborhoods. These changes, particularly in coding sequences, are most consistent with the operation of balancing selection and the antagonistic pleiotropy theory of aging and life history traits that tend to be intercorrelated. Genes involved in antioxidant defenses, along with multiple lncRNAs, were among those most affected by balancing selection. Despite the overwhelming genetic diversification and the paucity of selective sweep regions, two genes with functions important for central nervous system and memory, Ptp10D and Ank2, evolved under positive selection in the longevity lines. Overall, the 'evolve-and-resequence' experimental approach proves successful in providing unique insights into the complex evolutionary dynamics of genomic regions responsible for longevity (Michalak, 2017).

    Balancing selection drives the maintenance of genetic variation in Drosophila antimicrobial peptides

    Genes involved in immune defense against pathogens provide some of the most well-known examples of both directional and balancing selection. Antimicrobial peptides (AMPs) are innate immune effector genes, playing a key role in pathogen clearance in many species, including Drosophila. Conflicting lines of evidence have suggested AMPs may be under directional, balancing or purifying selection. This study used both a linear model and control gene-based approach to show that balancing selection is an important force shaping AMP diversity in Drosophila. In D. melanogaster, this is most clearly observed in ancestral African populations. Furthermore, the signature of balancing selection is even more striking once background selection has been accounted for. Balancing selection also acts on AMPs in D. mauritiana, an isolated island endemic separated from D. melanogaster by about 4 million years of evolution. This suggests that balancing selection may be broadly acting to maintain adaptive diversity in Drosophila AMPs, as has been found in other taxa (Chapman, 2019).

    Environmental dependence of mutational (co)variances of adaptive traits

    Standing genetic variation, and capacity to adapt to environment change, will ultimately depend on the fitness effects of mutations across the range of environments experienced by contemporary, panmictic, populations. This study investigated how mild perturbations in diet and temperature affect mutational (co)variances of traits that evolve under climatic adaptation, and contribute to individual fitness in Drosophila serrata. Egg-to-adult viability, development time and wing size were assessed of 64 lines that had diverged from one another via spontaneous mutation over 30 generations of brother-sister mating. The results suggested most mutations have directionally concordant (i.e., synergistic) effects in all environments and both sexes. However, elevated mutational variance under reduced macronutrient conditions suggested environment-dependent variation in mutational effect sizes for development time. Evidence was also observed for antagonistic effects under standard versus reduced macronutrient conditions, where these effects were further contingent on temperature (for development time) or sex (for size). Diet also influenced the magnitude and sign of mutational correlations between traits, although this result was largely due to a single genotype (line), which may reflect a rare, large effect mutation. Overall, these results suggest environmental heterogeneity and environment-dependency of mutational effects could contribute to the maintenance of genetic variance (Kannan, 2023).

    Annotation and Analysis of 3902 Odorant Receptor Protein Sequences from 21 Insect Species Provide Insights into the Evolution of Odorant Receptor Gene Families in Solitary and Social Insects

    The gene family of insect olfactory receptors (ORs) has expanded greatly over the course of evolution. ORs enable insects to detect volatile chemicals and therefore play an important role in social interactions, enemy and prey recognition, and foraging. The sequences of several thousand ORs are known, but their specific function or their ligands have only been identified for very few of them. To advance the functional characterization of ORs, this study has assembled, curated, and aligned the sequences of 3902 ORs from 21 insect species, which is provided as an annotated online resource. Using functionally characterized proteins from the fly Drosophila melanogaster, the mosquito Anopheles gambiae and the ant Harpegnathos saltator, amino acid positions were identified that best predict response to ligands. The conservation of these predicted relevant residues was examined in all OR subfamilies; the results showed that the subfamilies that expanded strongly in social insects had a high degree of conservation in their binding sites. This suggests that the ORs of social insect families are typically finely tuned and exhibit sensitivity to very similar odorants. The novel approach of this study provides a powerful tool to exploit functional information from a limited number of genes to study the functional evolution of large gene families (Mier, 2022).

    Genetic convergence in the evolution of male-specific color patterns in Drosophila

    Convergent evolution provides a type of natural replication that can be exploited to understand the roles of contingency and constraint in the evolution of phenotypes and the gene networks that control their development. For sex-specific traits, convergence offers the additional opportunity for testing whether the same gene networks follow different evolutionary trends in males versus females. Thus study used an unbiased, systematic mapping approach to compare the genetic basis of evolutionary changes in male-limited pigmentation in several pairs of Drosophila species that represent independent evolutionary transitions. A strong evidence for repeated recruitment of the same genes to specify similar pigmentation in different species was found. At one of these genes, ebony, convergent evolution of sexually dimorphic and monomorphic expression through cis-regulatory changes was observed. However, this functional convergence has a different molecular basis in different species, reflecting both parallel fixation of ancestral alleles and independent origin of distinct mutations with similar functional consequences. These results show that a strong evolutionary constraint at the gene level is compatible with a dominant role of chance at the molecular level (Signor, 2016).

    Recent studies have led to an emerging consensus that convergent phenotypes often reflect evolutionary changes in the same genes (the 'evolutionary hotspot' model). However, most case studies supporting the hotspot model relied heavily on candidate gene approaches, which results in a positive ascertainment bias and some difficulty in interpreting the results. Although genetic mapping is more laborious than candidate gene analysis, it offers several key advantages: it is unbiased in that the loci implicated in other species are no more likely to be discovered than any other genes, it produces direct evidence of a gene's causative role in trait evolution (and, equally importantly, allows other genes to be ruled out), and it provides a quantitative estimate of the relative importance of each gene to the overall genetic architecture of a phenotype. This study applied this approach to the ananassae species subgroup, in which multiple species have independently evolved similar male-specific color patterns. The convergent phenotypes were found ti be controlled by overlapping, but not identical, sets of genes in different evolutionary contrasts. The only gene that was implicated in all three high-resolution mapping crosses and could not be ruled out in the fourth, low-resolution cross (D. m. malerkotliana/D. bipectinata) was ebony. Moreover, ebony is the strongest QTL in all contrasts, contributing 35% to 80% of overall divergence. ebony has previously been implicated in both intraspecific and interspecific differences in pigmentation in several other Drosophila species. Clearly, ebony fits the definition of an evolutionary hotspot. ebony encodes an enzyme, β-alanyl-dopamine synthase, that synthesizes light pigment precursors so that higher ebony expression causes lighter pigmentation. Like other pigmentation genes, it has additional roles in other tissues, such as control of circadian locomotor activity in brain glial cells. Every time ebony has been implicated in the evolution of pigmentation, cis-regulatory rather than coding mutations were involved. Presumably, this pattern reflects the ability of cis-regulatory mutations to overcome pleiotropic constraints by uncoupling gene functions in different cell types (Signor, 2016).

    Repeated involvement of the same gene in multiple phenotypic transitions could potentially result from different evolutionary processes: recurrent de novo mutation, lineage sorting of ancestral variation, or interspecific introgression. Adaptation from standing variation is likely to be faster than awaiting a new mutation because potentially beneficial alleles are available immediately and are likely to be present at higher frequencies than alleles arising de novo. Cases of parallel fixation appear to be fairly common, most notably when a reservoir of newly adaptive alleles is available to colonizing populations. Similarly, introgressive hybridization has been implicated, among other traits, in the evolution of wing color patterns in Heliconius butterflies and high-altitude adaptation in humans. Genome-wide analyses suggest that interspecific introgression may play a more important role in evolution than previously thought. This study found that in D. malerkotliana, D. bipectinata, and D. parabipectinata, at least some of the putative causative SNPs at the ebony locus are shared across species, most likely reflecting ancestral lineage sorting. However, these variants are not found either in D. pseudoananassae or in the ercepeae species complex, suggesting a role for independent ebony mutations in these taxa. The region of the ebony locus associated with the evolution of color patterns in the bipectinata complex evolves so rapidly that it cannot be aligned with other taxa. Outside of the ananassae subgroup, evolutionary changes in ebony expression that lead to divergent pigmentation map to a different, more upstream region of the gene; population-genetic analysis rules out this region in the bipectinata complex. It can be concluded that the widely convergent involvement of ebony in the evolution of color patterns is not due solely to fixation of pre-existing variation, but reflects independent origin of distinct, though functionally similar, cis-regulatory mutations (Signor, 2016).

    Cuticle color depends not just on the level of ebony, but on the balance between ebony, tan, yellow, and potentially other enzymes. For example, tan encodes a β-alanyl-dopamine hydrolase, which reverses the chemical reaction catalyzed by ebony. Although tan is implicated in the evolution of pigmentation in several species, it has been ruled out in many other studies including this one (Table S5). Interestingly, the evolutionary changes that were found to involve tan are never male limited; for example, tan controls a female-limited color polymorphism in D. erecta, and the secondary loss of pigmentation in D. santomea affects both sexes. It is possible that ebony could be favored as the male hotspot due to its dosage sensitivity and chromosomal location. ebony, but not tan or yellow, has a semi-dominant loss-of-function phenotype, suggesting that cis-regulatory mutations in ebony could be more readily visible to directional selection. At the same time, yellow and tan are X-linked, whereas ebony is autosomal, suggesting that it could harbor higher levels of standing genetic variation when not under directional selection. Interestingly, in D. melanogaster, D. americana, and the bipectinata species complex, the role of ebony in phenotypic evolution appears to derive from a combination of pre-existing and de novo mutations. Thus, chromosomal sex, the topology of the regulatory network, the kinetics of the pigment synthesis pathway, and population-genetic factors may all contribute to the evolutionary hotspot status of ebony (Signor, 2016).

    In an accompanying paper (Yassin, 2016), a similarly unbiased and systematic approach was taken to map the genetic basis of natural variation in female-specific abdominal pigmentation in multiple species of the Drosophila montium species subgroup, which is closely related to the ananassae lineage. This variation was found to map to the pdm3 transcription factor in several distantly related species. Moreover, convergent involvement of pdm3 appears to reflect independent mutations in this gene in different species. In contrast, ebony does not contribute to color pattern variation in any of the four montium-subgroup species examined. Why do evolutionary hotspots differ in closely related lineages? Is this a matter of historical contingency or different gene network topology in different clades? Or are different genes within a shared network favored for cis-regulatory evolution in different sexes, resulting in sex-specific evolutionary hotspots? Intriguingly, in the only montium subgroup species in which ebony was implicated in color pattern variation, the pigmentation phenotype is male specific, supporting the latter hypothesis (Signor, 2016).

    One can envision two principal mechanisms for the gain and loss of sex-specific traits. First (the instructive model), the genes responsible for phenotypic changes may be the same genes that are regulated in a dimorphic manner to generate sex-specific phenotypes, as was observed for ebony. Alternatively (the permissive model), the causative genes could be monomorphic, while sexual dimorphism is encoded in parallel to or downstream of these genes. For example, ebony could have been expressed equally between sexes in all species, while a different, 'gatekeeper' gene is sexually dimorphic in all species. In the latter scenario, high levels of ebony expression in both sexes would mask the dimorphic phenotypes promoted by the sex-specific gatekeeper gene, while low ebony levels would uncover the underlying dimorphism. Thus, ebony would be the causative gene responsible for differences between lineages, while the gatekeeper gene is responsible for sexual dimorphism (Signor, 2016).

    These two models suggest very different mechanisms for the evolution of sexual dimorphism. Under the instructive model, gain and loss of sex-specific traits is caused by frequent changes in sex-specific gene regulation. Under the permissive model, the targets of the sex determination pathway can remain static over long evolutionary distances, while the underlying sexual dimorphism is revealed or obscured by sexually monomorphic genetic changes that occur elsewhere in the developmental pathway (Signor, 2016).

    The current results argue for the instructive model: in all evolutionary contrasts, sex-specific pigmentation is associated with sex-specific ebony expression, and sexually monomorphic pigmentation is associated with monomorphic expression. Thus, sex-specific transcriptional regulation of ebony has been gained and/or lost several times within the ananassae species subgroup. A similar pattern has been observed in the expression of desat-F, a hydrocarbon desaturase enzyme involved in the synthesis of cuticular pheromones. It appears that sex-specific gene regulation can be gained and lost quite easily over short evolutionary timescales and that the evolution of sexually dimorphic traits is more likely to follow the instructive model (Signor, 2016).

    Although the study of color pattern evolution in Drosophila has largely been dominated by candidate gene analyses, it has now been enriched by several unbiased, high-resolution genetic mapping studies, including this work. These studies have gone beyond spotlighting individual genes to provide a more holistic picture of the genetic architecture of evolutionary changes and have confirmed the predominance of cis-regulatory mutations in phenotypic evolution. Although no single gene is involved in all cases, the number of players appears to be limited, and most genes have been implicated repeatedly in multiple taxa. Collectively, parallel genetic analyses in multiple species suggest a 'toolkit model' of convergent evolution. For any trait, there are a limited number of genes that can potentially evolve to produce phenotypic changes. Within that toolkit, the relative likelihood of each gene's involvement may depend on its position in the regulatory network that controls the development of that trait, on the historical contingencies specific to each evolving lineage, and, potentially, on sex. Together, these trends result in a pattern where convergent phenotypes have distinct yet overlapping genetic basis in different species (Signor, 2016).

    Patterning the insect eye: From stochastic to deterministic mechanisms

    While most processes in biology are highly deterministic, stochastic mechanisms are sometimes used to increase cellular diversity. In human and Drosophila eyes, photoreceptors sensitive to different wavelengths of light are distributed in stochastic patterns, and one such patterning system has been analyzed in detail in the Drosophila retina. Interestingly, some species in the dipteran family Dolichopodidae (the "long legged" flies, or "Doli") instead exhibit highly orderly deterministic eye patterns. In these species, alternating columns of ommatidia (unit eyes) produce corneal lenses of different colors. Occasional perturbations in some individuals disrupt the regular columns in a way that suggests that patterning occurs via a posterior-to-anterior signaling relay during development, and that specification follows a local, cellular-automaton-like rule. It is hypothesized that the regulatory mechanisms that pattern the eye are largely conserved among flies and that the difference between unordered Drosophila and ordered dolichopodid eyes can be explained in terms of relative strengths of signaling interactions rather than a rewiring of the regulatory network itself. A simple stochastic model is presented that is capable of explaining both the stochastic Drosophila eye and the striped pattern of Dolichopodidae eyes and thereby characterize the least number of underlying developmental rules necessary to produce both stochastic and deterministic patterns. Only small changes to model parameters are needed to also reproduce intermediate, semi-random patterns observed in another Doli species, and quantification of ommatidial distributions in these eyes suggests that their patterning follows similar rules (Ebadi, 2018).

    A Continuum of Evolving De Novo Genes Drives Protein-Coding Novelty in Drosophila

    Orphan genes, lacking detectable homologs in outgroup species, typically represent 10-30% of eukaryotic genomes. This study investigated the roots of orphan gene emergence in the Drosophila genus. Across the annotated proteomes of twelve species, 6297 orphan genes were found within 4953 taxon-specific clusters of orthologs. By inferring the ancestral DNA as non-coding for between 550 and 2467 (8.7-39.2%) of these genes, this study describes for the first time how de novo emergence contributes to the abundance of clade-specific Drosophila genes. In support of them having functional roles, it was shown that de novo genes have robust expression and translational support. However, the distinct nucleotide sequences of de novo genes, which have characteristics intermediate between intergenic regions and conserved genes, reflect their recent birth from non-coding DNA. It was found that de novo genes encode more disordered proteins than both older genes and intergenic regions. Together, these results suggest that gene emergence from non-coding DNA provides an abundant source of material for the evolution of new proteins. Following gene birth, gradual evolution over large evolutionary timescales moulds sequence properties towards those of conserved genes, resulting in a continuum of properties whose starting points depend on the nucleotide sequences of an initial pool of novel genes (Heames, 2020).

    Evolution of herbivory in Drosophilidae linked to loss of behaviors, antennal responses, odorant receptors, and ancestral diet

    Herbivory is a key innovation in insects, yet has only evolved in one-third of living orders. The evolution of herbivory likely involves major behavioral changes mediated by remodeling of canonical chemosensory modules. Herbivorous flies in the genus Scaptomyza (Drosophilidae) are compelling species in which to study the genomic architecture linked to the transition to herbivory because they recently evolved from microbe-feeding ancestors and are closely related to Drosophila melanogaster. This study found that Scaptomyza flava, a leaf-mining specialist on plants in the family (Brassicaceae), was not attracted to yeast volatiles in a four-field olfactometer assay, whereas D. melanogaster was strongly attracted to these volatiles. Yeast-associated volatiles, especially short-chain aliphatic esters, elicited strong antennal responses in D. melanogaster, but weak antennal responses in electroantennographic recordings from S. flava. The genome of S. flava was sequenced, and this species' odorant receptor repertoire was characterized. Orthologs of odorant receptors, which detect yeast volatiles in D. melanogaster and mediate critical host-choice behavior, were deleted or pseudogenized in the genome of S. flava. These genes were lost step-wise during the evolution of Scaptomyza. Additionally, Scaptomyza has experienced gene duplication and likely positive selection in paralogs of Or67b in D. melanogaster. Olfactory sensory neurons expressing Or67b are sensitive to green-leaf volatiles. Major trophic shifts in insects are associated with chemoreceptor gene loss as recently evolved ecologies shape sensory repertoires (Goldman-Huertas, 2005).

    Understanding the origins and consequences of trophic shifts, especially the transition to herbivory, has been a central problem in evolutionary biology. The paleontological record suggests that evolutionary transitions to herbivory have been rare in insects, and the first transitions to herbivory in vertebrates occurred long after the colonization of land. However, species radiations result from herbivorous transitions in insects and vertebrates, suggesting that herbivory is a key innovation. Identifying functional genomic changes associated with the evolutionary transition to herbivory could yield insight into the mechanisms that have driven their success. However, the origins of the most diverse clades of herbivorous insects are ancient and date to the Jurassic or earlier, limiting meaningful genomic comparisons. In contrast, herbivory has evolved more times in Diptera than in any other order. The Drosophilidae is an excellent system to study the evolution of herbivory from a functional genomic perspective because it includes several transitions to herbivory, and the genomic model Drosophila melanogaster (Goldman-Huertas, 2005).

    The transition to herbivory involves adaptations in physiology, morphology, and behavior. The evolution of sensory repertoires could reinforce or even precipitate these adaptations through adaptive loss or relaxation of functional constraint subsequent to a trophic shift. Adaptive loss of chemoreceptors has been rarely shown but occurs in nematodes, although their olfactory systems are distinct from insects. Families of mammalian olfactory receptor proteins have been remodeled during transitions to flight, aquatic lifestyles, and frugivory. Similarly, the evolution of diet specialization in Drosophila species correlates with chemoreceptor gene losses, and hematophagous flies have lost gustatory receptors that detect sweet compounds. More profound changes such as the evolution of new protein families are associated with major evolutionary transitions such as the evolution of flight in insects. Although gene loss is unlikely to be a driving force of innovation, loss-of-function mutations may be exeptations that allow novel behaviors to evolve by disrupting ancestral attractions. If detection of different chemical cues becomes selected in a novel niche, then loss through relaxed constraint may indicate which chemical cues have changed during a trophic shift (Goldman-Huertas, 2005).

    The chemosensory repertoires of many drosophilid species have been functionally annotated. The genus Drosophila includes 23 species with published genome sequences, and D. melanogaster presents the most fully characterized insect olfactory system, allowing potential linkage of receptor remodeling to a mechanistic understanding of behavioral change (Goldman-Huertas, 2005).

    Most drosophilids feed on yeast and other microbes growing on decaying plant tissues. Adult female D. melanogaster and distantly related species innately prefer yeast chemical cues to those produced by the fruit on which they oviposit. D. melanogaster detects volatiles with chemoreceptors of several different protein families, but especially receptors from the odorant receptor (OR) gene family, some of which, such as Or42b, are highly conserved across species. Or42b is necessary for attraction and orientation to vinegar and aliphatic esters. Similar compounds activate Or42b across many Drosophila species, suggesting that volatile cues for yeast, and the associated receptors, are conserved across the Drosophilidae (Goldman-Huertas, 2005).

    The ancestral feeding niche for the genus Scaptomyza (Drosophilidae) is microbe-feeding, but Scaptomyza use decaying leaves and stems rather than the fermenting fruit used by D. melanogaster and other members of the subgenus Sophophora. The close association of Scaptomyza with decaying plant tissues may have precipitated the evolution of herbivory <20 MyBP. Adult females of the species S. flava feed and oviposit on living leaves of many cruciferous plants (Brassicales) including Arabidopsis thaliana. Females puncture leaves with serrated ovipositors to create feeding and oviposition sites, and larvae mine and pupate within the living leaves (Goldman-Huertas, 2005).

    This study used Scaptomyza as a model to test the hypothesis that functional loss of chemosensory genes has played a role in a major ecological transition to herbivory in insects. It was hypothesized that the conserved detection of yeast volatiles would be lost in the herbivorous Scaptomyza lineage. This loss was tested by comparing D. melanogaster and S. flava at behavioral, physiological, and genetic levels. First, it was hypothesized that gravid ovipositing S. flava females would not be attracted to yeast volatiles. Second, it was hypothesized that the olfactory sensory organs of S. flava would have a decreased ability to detect individual yeast volatiles and volatile mixtures. Third, chemoreceptor genes from the OR gene family implicated in detection of yeast volatiles would be lost in the S. flava genome. Finally, it was predicted that chemoreceptor genes potentially mediating detection of plant volatiles would show evidence of positive selection and possibly, neofunctionalization (Goldman-Huertas, 2005).

    Olfaction is used by insects to find resources, mates, and oviposition substrates. This study tested the hypothesis that S. flava is not attracted to yeast volatiles, whereas D. melanogaster is attracted to yeast volatiles. A four-field olfactometer assay was used in which filtered air blown through four corners of a diamond-shaped arena establishes four independent airfields. Two of the four fields were exposed to yeast volatiles from Saccharomyces cerevisiae cultures. The presence of gravid adult females of both species in either yeast or control fields was recorded every 6 s for 10 min. D. melanogaster flies spent 82.4 ± 18.2% SD of the assay time in yeast-volatile fields and more time in yeast-volatile fields than S. flava. S. flava did not spend more time in yeast-volatile fields and divided residence time evenly between yeast and control fields, consistent with a loss of attraction to yeast volatiles in S. flava flies (Goldman-Huertas, 2005).

    Because S. flava flies failed to increase their residence time in olfactometer quadrants exposed to yeast volatiles, it was hypothesized that S. flava antennal olfactory sensory neurons (OSNs) were deficient in their ability to detect yeast volatiles. This hypothesis was tested by conducting electroantennogram (EAG) measurements in adult D. melanogaster and S. flava flies of both sexes 4-20 d after eclosion, exposed to the same yeast volatiles used in the olfactometer assays and to crushed rosette leaves of the host plant of S. flava flies in laboratory colonies (Arabidopsis thaliana accession Col-0). EAG responses are driven by the aggregate depolarization of OSNs in the antennae and scale with the concentration and identity of stimulants. No difference were found between sexes and data for male and female flies were combined. Consistently lower EAG signals were recorded in S. flava flies compared with D. melanogaster, preventing interspecific comparisons of signal amplitude, possibly due to differences in electrical properties of antennae (Goldman-Huertas, 2005).

    The antennae of S. flava were more strongly stimulated by Arabidopsis volatiles than by yeast, whereas the antennae of D. melanogaster were more responsive to volatiles from yeast than those from Arabidopsis. Responses were recorded to a small panel of three volatiles associated with A. thaliana [(Z)-3-hexenol, myrcene, phenethyl isothiocyanate] and two with S. cerevisiae (2-phenylethanol, ethyl acetate). Antennae of both species detected all volatiles compared with a negative control. The antennae of S. flava were most responsive to (Z)-3-hexenol, a volatile produced by damaged leaves of many plant species, and were also highly attuned to phenethyl isothiocyanate, a hydrolyzed product of glucosinolates, which are the major defensive compound in host plants of S. flava. Responses to myrcene and 2-phenylethanol were not in the expected direction, although 2-phenylethanol, as a widespread floral volatile, may remain an important chemical cue for Scaptomyza adults (Goldman-Huertas, 2005).

    Antennae of S. flava were less responsive to yeast and the yeast-associated volatile ethyl acetate than to plant-related volatiles, but these relative comparisons were insufficient to prove that the detection threshold for yeast volatiles had decreased in Scaptomyza. Therefore the sensitivity of S. flava and D. melanogaster flies to this and other short-chain aliphatic esters was tested by exposing females to half-log dilution series of ethyl acetate, ethyl propionate, and isobutyl acetate. Sensitivity was defined as the first concentration increase that generated an increased antennal response. S. flava was insensitive to ethyl acetate at the concentrations tested. S. flava was also less responsive to ethyl propionate and isobutyl acetate compared with D. melanogaster. Scaptomyza is considerably less sensitive to short aliphatic esters, which may account for differences in signal strength in response to plant and yeast volatile mixtures and the lack of attraction to yeast volatiles by S. flava. This unresponsiveness is consistent with the fact that deficits in the production of aliphatic esters in a yeast strain decreased attractiveness to D. melanogaster flies (Goldman-Huertas, 2005).

    The lack of attraction and minimal EAG response to yeast volatiles in S. flava suggested that chemosensory genes have been lost or changed in herbivorous Scaptomyza species. ORs are expressed in the dendrites of OSNs in the antennae and maxillary palps and are the primary receptors by which most neopteran insects detect odors in their environments. The OR family has been functionally annotated in D. melanogaster, and members of subfamily H OR genes in particular are highly conserved and enriched in receptors for aliphatic esters, a group of compounds S. flava detected poorly (Goldman-Huertas, 2005).

    To characterize changes in the OR gene repertoire in S. flava associated with the olfactory phenotypes, the genome of S. flava and annotated OR genes were annotated by using reciprocal tBLASTn searches of previously annotated Drosophila OR protein sequences against this de novo S. flava genome assembly. 65 full-length ORFs for OR genes were found in S. flava. Consistent with previous OR gene-naming conventions, ORs were named after the D. melanogaster ortholog or the most closely related gene, with the exception of OrN1 and OrN2 orthologs, which are not present in D. melanogaster (Goldman-Huertas, 2005).

    Protein translations of S. flava genes were included in a phylogeny of D. melanogaster, Drosophila virilis, Drosophila mojavensis, and Drosophila grimshawi OR protein sequences to assess homology. The latter three species are the closest relatives of Scaptomyza with fully sequenced genomes (Goldman-Huertas, 2005).

    S. flava retains duplicates of Or42a, Or67a, Or74a, Or83c, Or98a, and OrN2 found in other sequenced Drosophila species. Scaptomyza also has duplications not shared with close relatives, although nine of these genes are pseudogenized. The majority of paralogs (56%) were found on the same scaffold in tandem arrays. The functional significance of these gene duplications is not yet clear, but it is suggestive that Or67b, with three copies in S. flava, is in single copy in nearly all sequenced Drosophila. In D. melanogaster, neurons expressing Or67b respond to green leaf volatiles such as (Z)-3-hexenol, to which S. flava also has a robust antennal response (Goldman-Huertas, 2005).

    Only four widely conserved ORs were uniquely lost (Or22a and Or85d) or pseudogenized (Or9a, Or42b) in the Scaptomyza lineage. Syntenic regions flanking OR losses were recovered in the genome assembly. Orthologs of Or9a, Or22a, and Or42b are intact in 23 Drosophila species with genome sequences, and Or85d is missing only in the Drosophila albomicans and Drosophila rhopaloa genome assemblies. As predicted, orthologs of ORs that persist in microbe-feeding Drosophila species and are lost in S. flava, function in yeast-volatile detection. Or42b is highly conserved in sequence among Drosophila species, and the receptor is highly attuned to aliphatic esters at low concentrations. Knockouts of Or42b in adult D. melanogaster result in failure to orient in flight toward aliphatic ester odor plumes , and rescuing these neurons restores attraction to yeast volatiles. Similarly, no sequences similar to Or22a were present in the S. flava assembly, although conserved intergenic regions were found in S. flava that flank Or22a in other Drosophila species. Or22a also detects aliphatic esters and in the specialist species Drosophila erecta and Drosophila sechellia, Or22a detects volatiles produced by host fruit. Both Or22a and Or42b are activated by floral volatiles of Arum palestinum, which mimics yeast fermentation volatiles and attracts a diversity of drosophilids. Finally, Or85d orthologs were not detected in the S. flava genome by BLAST or by inspection of genome regions flanking Or85d in other species. Or85d is expressed in the maxillary palps and in D. melanogaster is responsive to the yeast metabolites 2-heptanol, ethyl acetate, and isoamyl acetate. Or85d is highly sensitive to phenethyl acetate, a common volatile of many yeast species. In D. melanogaster, Or9a is activated by a broad range of ketone-, alcohol-, and carboxylic acid-containing ligands. Some of these ligands, such as acetoin, are common yeast volatiles and strong attractants. The consequences of Or9a pseudogenization will require further study (Goldman-Huertas, 2005).

    A time-calibrated phylogeny of the family Drosophilidae suggests that herbivory evolved in Scaptomyza ca.13.5 million years ago (95% highest posterior density 10.02–17.48 million years ago), overlapping with age ranges inferred from previous analyses. Ancestral state reconstructions were performed in the APE package by using an equal rates model. This analysis indicated that microbe feeding is ancestral in Drosophila and Scaptomyza (99.7% probability) and that herbivory evolved once within the genus Scaptomyza (Goldman-Huertas, 2005).

    It was hypothesized that OR gene losses would coincide with the evolution of herbivory. Degenerate PCR primers were developed from genomes of multiple Scaptomyza and Drosophila species that targeted exonic sequences of Or22a and Or9a, and conserved, flanking, intergenic sequences of Or42b and Or85d (Goldman-Huertas, 2005).

    Gene losses in S. flava were confirmed by PCR screen in three natural populations, with the exception of SflaOr9a-1, which appeared to be present in a functional copy in a population from Arizona. A preliminary genome assembly of Scaptomyza pallida was consistent with PCR screening results for OR loss patterns in this species. The presence/absence of S. flava gene losses was reconstructed along ancestral nodes and found that three of the four OR gene losses in S. flava (Or22a, Or85d, Or42b) coincided with or preceded the evolution of herbivory in Scaptomyza. Losses were shared by herbivorous congeners. Or22a, while lost in S. flava, is intact in the microbe-feeding species Scaptomyza apicata and S. pallida and is also lost in two other herbivorous species, Scaptomyza nigrita and Scaptomyza graminum (Goldman-Huertas, 2005).

    Specialist, microbe-feeding Drosophila species, such as D. sechellia and D. erecta have an accelerated rate of chemoreceptor gene loss, but this pattern could also be due to nearly neutral processes. S. flava feeds almost exclusively on plants within the Brassicales, and it was hypothesized that this species has experienced an accelerated rate of chemosensory gene loss compared with other microbe-feeding Drosophila species. This hypothesis was tested by coding homologous groups of ORs as present or absent in S. flava, D. virilis, D. mojavensis and D. grimshawi (the closest Drosophila relatives of Scaptomyza), and two models of gene loss were inferred in the Brownie software package. No evidence was found for the alternative model of increased rate of loss in Scaptomyza, but it cannot be ruled out that there were insufficient loss events to parameterize the more complex model or that other chemoreceptor gene families have undergone accelerated loss in S. flava. Also, S. flava is oligophagous, feeding on many plant species in the Brassicales, and it is less specialized than D. sechellia and D. erecta (Goldman-Huertas, 2005).

    Because the shift to herbivory in Scaptomyza likely involved many changes in olfactory cues, it was hypothesized that some S. flava OR genes should bear signatures of episodic positive selection, as flies adapted to a novel environment. To test this hypothesis, null and alternative (branch-site) models were inferred in PAML 4.7a where subsets of codons in extant S. flava ORs could evolve under (i) purifying or neutral selection or (ii) purifying, neutral, or positive selection, relative to 12 Drosophila species. A phylogeny-aware alignment program, PRANK, was used to identify regions where indels were probable while minimizing sensitivity to alignment errors. Alignments where more than one taxon had an inferred indel in greater than two regions were trimmed by using Gblocks to remove columns with ambiguous homology(Goldman-Huertas, 2005).

    After correcting for false discovery, two ORs were found in which the branch-site model consistent with episodic positive selection was more likely than the null model. Or88a had the strongest statistical support for the branch-site model. In D. melanogaster, Or88a functions in recognition of male and virgin female conspecifics . Two other branches among the S. flava Or67b paralogs also supported the branch-site model: an ancestral branch preceding a Scaptomyza-specific duplication event and a branch leading to Or67b-3. Homologs of this gene in D. melanogaster encode ORs that respond to the green-leaf volatile (Z)-3-hexenol, one of the most salient ligands found in EAG studies of S. flava. Experimental, functional, and population-based tests are needed to verify whether positive selection has fixed amino acid changes in the Scaptomyza lineage (Goldman-Huertas, 2005).

    It is concluded that trophic transitions in the history of animal life, such as herbivory, may be mediated by genetic changes in chemosensory repertoires. The majority of Drosophilidae feed on microbes, and distantly related drosophilid lineages are attracted by the same yeast-mimicking floral scent produced by A. palestinum. A subset of the ORs stimulated by this scent are highly conserved in other drosophilids, which may be part of a homologous and conserved olfactory circuit used to find fermenting host substrates across the family. It was hypothesized that mutations disrupting the function of OR homologs in this conserved olfactory circuit could mediate the evolution of herbivory or other novel food preferences (Goldman-Huertas, 2005).

    S. flava, an herbivorous drosophilid, has lost orthologs of ORs involved in this generalized yeast olfactory circuit. Consistent with these findings, S. flava did not respond to yeast volatiles in a behavioral assay. Antennae of S. flava were weakly activated by active yeast cultures and short-chain aliphatic esters, key compounds found in yeast volatile blends and known ligands of ORs in D. melanogaster lost in S. flava. However, retention of some ORs implicated in yeast-volatile detection, such as Or92a and Or59b, implies that S. flava may retain the ability to detect some untested yeast compounds (Goldman-Huertas, 2005).

    It is hypothesized that OR genes would be intact in nonherbivorous Scaptomyza and gene losses would coincide with the transition to herbivory. Or22a loss did coincide with the evolution of herbivory, but losses of Or42b and Or85d likely predate the evolution of plant feeding. These more ancient losses of conserved yeast-volatile receptors suggest ancestral Scaptomyza may have already evolved novel olfactory pathways that were later co-opted by herbivorous lineages, and in fact, many Scaptomyza species feed on microbes living within decaying leaves or in leaf mines produced by other insects. Sister groups of many major herbivorous insect lineages also feed on detritus and fungi, suggesting that the transition from microbe feeding to herbivory may be common. The genetic changes that underlie host-finding remain to be identified, but recently duplicated ORs, such as the unique triplication of Or67b in Scaptomyza, are likely candidates for further functional study. Subtle, targeted remodeling of chemoreceptor repertoires may be a general mechanism driving changes in behavior, facilitating trophic shifts and ultimately diversification in animals (Goldman-Huertas, 2005).

    Molecular and functional evolution at the Odorant receptor Or22 locus in Drosophila melanogaster

    Insect odorant receptor (Or) genes determine the responses of sensory neurons that mediate critical behaviours. The Drosophila melanogaster Or22 locus represents an interesting example of molecular evolution, with high levels of sequence divergence and copy number variation between D. melanogaster and other Drosophila species, and a corresponding high level of variability in the responses of the neuron it controls, ab3A. However, the link between Or22 molecular and functional diversity has not been established. This study shows that several naturally occurring Or22 variants generate major shifts in neuronal response properties. The molecular changes were determined that underpin these response shifts, one of which represents a chimaeric gene variant previously suggested to be under natural selection. In addition it was shown that several alternative molecular genetic mechanisms have evolved for ensuring that where there is more than one gene copy at this locus, only one functional receptor is generated. These data thus provide a causal link between the striking levels of phenotypic neuronal response variation found in natural populations of D. melanogaster and genetic variation at the Or22 locus. Since neuronal responses govern animal behaviour, it is predicted that Or22 may be a key player in underlying one or more olfactory-driven behaviours of significant adaptive importance (Shaw, 2019).

    Color preference of the spotted wing Drosophila, Drosophila suzukii

    Drosophila suzukii Matsumura (Diptera: Drosophilidae) is a significant invasive pest in soft-skin fruits and berries in Asia, Europe, and North and South America. Many herbivorous insects use multiple cues for host selection, particularly olfactory and visual stimuli. The visual system of closely-related Drosophila melanogaster is well-documented, expressing strong sensitivity to short-wavelength colors (ultraviolet to green) and only limited sensitivity to long-wavelength colors (red to infrared). The results suggest that D. suzukii have limited ability to distinguish red consistent with visual sensitivity range within the melanogaster subgroup. It is proposed that color contrast rather than color appearance may be of greater importance in orientation and attraction. It is proposed that differences in reflectance between light wavelengths important for color opponency are key to color discrimination to provide color contrast between foreground and background, as occurs between fruit and foliage, during host-finding (Little, 2019).

    The loci of behavioral evolution: evidence that Fas2 and tilB underlie differences in pupation site choice behavior between Drosophila melanogaster and D. simulans

    The behaviors of closely related species can be remarkably different, and these differences have important ecological and evolutionary consequences. While the recent boom in genotype-phenotype studies has led to a greater understanding of the genetic architecture and evolution of a variety of traits, studies identifying the genetic basis of behaviors are, comparatively, still lacking. This is likely because they are complex and environmentally sensitive phenotypes, making them difficult to measure reliably for association studies. The Drosophila species complex holds promise for addressing these challenges, as the behaviors of closely related species can be readily assayed in a common environment. This study investigated the genetic basis of an evolved behavioral difference, pupation site choice, between Drosophila melanogaster and D. simulans. In this study, A significant contribution was demonstrated of the X chromosome to the difference in pupation site choice behavior between these species. Using a panel of X-chromosome deficiencies, the majority of the X chromosome was screened for causal loci, and two regions were identified associated with this X-effect. Gene disruption and RNAi data were collecting supporting a single gene that affects pupation behavior within each region: Fas2 and tilB. Finally, differences in tilB expression were shown to correlate with the differences in pupation site choice behavior between species. This evidence associating two genes with differences in a complex, environmentally sensitive behavior represents the first step towards a functional and evolutionary understanding of this behavioral divergence (Pischedda, 2019).

    Back to the light, coevolution between vision and olfaction in the "Dark-flies" (Drosophila melanogaster)

    Trade-off between vision and olfaction, the fact that investment in one correlates with decreased investment in the other, has been demonstrated by a wealth of comparative studies. However, there is still no empirical evidence suggesting how these two sensory systems coevolve, i.e. simultaneously or alternatively. The "Dark-flies" (Drosophila melanogaster) constitute a unique model to investigate such relation since they have been reared in the dark since 1954, approximately 60 years (~1500 generations). To observe how vision and olfaction evolve, populations of Dark-flies were reared in normal lighting conditions for 1 (DF1G) and 65 (DF65G) generations. The sizes of the visual (optic lobes, OLs) and olfactory (antennal lobes, ALs) primary centres, as well as the rest of the brain, and compared the results with the original and its genetically most similar strain (Oregon flies). Whereas the ALs decreased in size, the OLs (together with the brain) increased in size in the Dark-flies returned back to the light, both in the DF1G and DF65G. These results experimentally show that trade-off between vision and olfaction occurs simultaneously, and suggests that there are possible genetic and epigenetic processes regulating the size of both optic and antennal lobes. Furthermore, although the Dark-flies were able to mate and survive in the dark with a reduced neural investment, individuals being returned to the light seem to have been selected with reinvestment in visual capabilities despite a potential higher energetic cost (Ozer, 2020).

    Olfactory receptor and circuit evolution promote host specialization

    The evolution of animal behaviour is poorly understood. Despite numerous correlations between interspecific divergence in behaviour and nervous system structure and function, demonstrations of the genetic basis of these behavioural differences remain rare. This study develop a neurogenetic model, Drosophila sechellia, a species that displays marked differences in behaviour compared to its close cousin Drosophila melanogaster that are linked to its extreme specialization on noni fruit (Morinda citrifolia). Using calcium imaging, this study identified olfactory pathways in D. sechellia that detect volatiles emitted by the noni host. This mutational analysis indicates roles for different olfactory receptors in long- and short-range attraction to noni, and cross-species allele-transfer experiments demonstrate that the tuning of one of these receptors is important for species-specific host-seeking. The molecular determinants of this functional change were identified, and their evolutionary origin and behavioural importance were characterized. Circuit tracing was performed in the D. sechellia brain, and receptor adaptations were found to be accompanied by increased sensory pooling onto interneurons as well as species-specific central projection patterns. This work reveals an accumulation of molecular, physiological and anatomical traits that are linked to behavioural divergence between species, and defines a model for investigating speciation and the evolution of the nervous system (Auer, 2020).

    A courtship behavior that makes monandrous females polyandrous

    Females of many animal species mate several times with different males (polyandry), whereas females of some species mate with a single male (monandry) only once. Little is known about the mechanisms by which these different mating systems evolve. Females of Drosophila prolongata mate serially, unlike Drosophila melanogaster females that refuse to remate for several days after their first mating (remating suppression [RS]). Nevertheless, interestingly, nonvirgin D. prolongata females refuse to remate with males that are prohibited from performing their species-specific courtship behavior, leg vibration (LV), suggesting that LV overrides RS making it cryptic in D. prolongata. This study examined how long this cryptic RS persists. Surprisingly, it was sustained for at least 2 weeks, showing that RS is substantially augmented in D. prolongata compared to that of D. melanogaster. The two most closely related species to D. prolongata, Drosophila rhopaloa and Drosophila carrolli, do not perform LV and showed augmented RS, supporting the idea that augmented RS could have evolved before LV was acquired. These results suggested that D. prolongata females are intrinsically monandrous, whereas the newly evolved courtship behavior makes them polyandrous. This is a rare case in which a proximate mechanism of polyandry evolution from monandry is demonstrated (Minekawa, 2020).

    Competitive history shapes rapid evolution in a seasonal climate

    Eco-evolutionary dynamics will play a critical role in determining species' fates as climatic conditions change. Unfortunately, there is little understanding of how rapid evolutionary responses to climate play out when species are embedded in the competitive communities that they inhabit in nature. The effects of rapid evolution in response to interspecific competition were tested on subsequent ecological and evolutionary trajectories in a seasonally changing climate using a field-based evolution experiment with Drosophila melanogaster. Populations of D. melanogaster were either exposed, or not exposed, to interspecific competition with an invasive competitor, Zaprionus indianus, over the summer. these populations' ecological trajectories (abundances) and evolutionary trajectories (heritable phenotypic change) were then quantified when exposed to a cooling fall climate. It was found that competition with Z. indianus in the summer affected the subsequent evolutionary trajectory of D. melanogaster populations in the fall, after all interspecific competition had ceased. Specifically, flies with a history of interspecific competition evolved under fall conditions to be larger and have lower cold fecundity and faster development than flies without a history of interspecific competition. Surprisingly, this divergent fall evolutionary trajectory occurred in the absence of any detectible effect of the summer competitive environment on phenotypic evolution over the summer or population dynamics in the fall. This study demonstrates that competitive interactions can leave a legacy that shapes evolutionary responses to climate even after competition has ceased, and more broadly, that evolution in response to one selective pressure can fundamentally alter evolution in response to subsequent agents of selection (Grainger, 2021).

    Sex ratio and the evolution of aggression in fruit flies

    Aggressive behaviours are among the most striking displayed by animals, and aggression strongly impacts fitness in many species. Aggression varies plastically in response to the social environment, but direct tests of how aggression evolves in response to intra-sexual competition are lacking. This study investigated how aggression in both sexes evolves in response to the competitive environment, using populations of Drosophila melanogaster that were experimentally evolved under female-biased, equal, and male-biased sex ratios. After evolution in a female-biased environment-with less male competition for mates-males fought less often on food patches, although the total frequency and duration of aggressive behaviour did not change. In females, evolution in a female-biased environment-where female competition for resources is higher-resulted in more frequent aggressive interactions among mated females, along with a greater increase in post-mating aggression. These changes in female aggression could not be attributed solely to evolution either in females or in male stimulation of female aggression, suggesting that coevolved interactions between the sexes determine female post-mating aggression. Evidence was found consistent with a positive genetic correlation for aggression between males and females, suggesting a shared genetic basis. This study demonstrates the experimental evolution of a behaviour strongly linked to fitness, and the potential for the social environment to shape the evolution of contest behaviours (Bath, 2021).

    Drosophila adaptation to viral infection through defensive symbiont evolution

    Microbial symbionts can modulate host interactions with biotic and abiotic factors. Such interactions may affect the evolutionary trajectories of both host and symbiont. Wolbachia protects Drosophila melanogaster against several viral infections and the strength of the protection varies between variants of this endosymbiont. Since Wolbachia is maternally transmitted, its fitness depends on the fitness of its host. Therefore, Wolbachia populations may be under selection when Drosophila is subjected to viral infection. This study shows that in D. melanogaster populations selected for increased survival upon infection with Drosophila C virus there is a strong selection coefficient for specific Wolbachia variants, leading to their fixation. Flies carrying these selected Wolbachia variants have higher survival and fertility upon viral infection when compared to flies with the other variants. These findings demonstrate how the interaction of a host with pathogens shapes the genetic composition of symbiont populations. Furthermore, host adaptation can result from the evolution of its symbionts, with host and symbiont functioning as a single evolutionary unit (Faria, 2016).

    Generality of toxins in defensive symbiosis: Ribosome-inactivating proteins and defense against parasitic wasps in Drosophila

    While it has become increasingly clear that multicellular organisms often harbor microbial symbionts that protect their hosts against natural enemies, the mechanistic underpinnings underlying most defensive symbioses are largely unknown. Spiroplasma bacteria are widespread associates of terrestrial arthropods, and include strains that protect diverse Drosophila flies against parasitic wasps and nematodes. Recent work implicated a ribosome-inactivating protein (RIP) encoded by Spiroplasma, and related to Shiga-like toxins in enterohemorrhagic Escherichia coli, in defense against a virulent parasitic nematode in the woodland fly, Drosophila neotestacea. This study tested the generality of RIP-mediated protection by examining whether Spiroplasma RIPs also play a role in wasp protection, in D. melanogaster and D. neotestacea. Strong evidence was found for a major role of RIPs, with ribosomal RNA (rRNA) from the larval endoparasitic wasps, Leptopilina heterotoma and Leptopilina boulardi, exhibiting the hallmarks of RIP activity. In Spiroplasma-containing hosts, parasitic wasp ribosomes show abundant site-specific depurination in the alpha-sarcin/ricin loop of the 28S rRNA, with depurination occurring soon after wasp eggs hatch inside fly larvae. Interestingly, the pupal ectoparasitic wasp, Pachycrepoideus vindemmiae, was found to escape protection by Spiroplasma, and its ribosomes do not show high levels of depurination. It was also shown that fly ribosomes show little evidence of targeting by RIPs. Finally, the genome of D. neotestacea's defensive Spiroplasma was found to encode a diverse repertoire of RIP genes, which are differ in abundance. This work suggests that specificity of defensive symbionts against different natural enemies may be driven by the evolution of toxin repertoires, and that toxin diversity may play a role in shaping host-symbiont-enemy interactions (Ballinger, 2017).

    An innovative ovipositor for niche exploitation impacts genital coevolution between sexes in a fruit-damaging Drosophila

    Limited attention has been given to ecological factors influencing the coevolution of male and female genitalia. The innovative ovipositor of Drosophila suzukii, an invading fruit pest, represents an appealing case to document this phenomenon. The serrated saw-like ovipositor is used to pierce the hard skin of ripening fruits that are not used by other fruit flies that prefer soft decaying fruits. This study highlights another function of the ovipositor related to its involvement in genital coupling during copulation. The morphology and coupling of male and female genitalia in this species were compared to its sibling species, Drosophila subpulchrella, and to an outgroup species, Drosophila biarmipes. These comparisons and a surgical manipulation indicated that the shape of male genitalia in D. suzukii has had to be adjusted to ensure tight coupling, despite having to abandon the use of a hook-like structure, paramere, because of the more linearly elongated ovipositor. This phenomenon demonstrates that ecological niche exploitation can directly affect the mechanics of genital coupling and potentially cause incompatibility among divergent forms. This model case provides new insights towards elucidating the importance of the dual functions of ovipositors in other insect species that potentially induce genital coevolution and ecological speciation (Muto, 2018).

    Neural evolution of context-dependent fly song

    It is unclear where in the nervous system evolutionary changes tend to occur. To localize the source of neural evolution that has generated divergent behaviors, a new approach was developed to label and functionally manipulate homologous neurons across Drosophila species. Homologous descending neurons were examined that drive courtship song in two species that sing divergent song types, and relevant evolutionary changes were localized in circuit function downstream of the intrinsic physiology of these descending neurons. This evolutionary change causes different species to produce divergent motor patterns in similar social contexts. Artificial stimulation of these descending neurons drives multiple song types, suggesting that multifunctional properties of song circuits may facilitate rapid evolution of song types (Ding, 2019).

    Enemies make you stronger: Coevolution between fruit fly host and bacterial pathogen increases postinfection survivorship in the host

    Multiple laboratory studies have evolved hosts against a nonevolving pathogen to address questions about evolution of immune responses (, 2021). However, an ecologically more relevant scenario is one where hosts and pathogens can coevolve. Such coevolution between the antagonists, depending on the mutual selection pressure and additive variance in the respective populations, can potentially lead to a different pattern of evolution in the hosts compared to a situation where the host evolves against a nonevolving pathogen. This study used Drosophila melanogaster as the host and Pseudomonas entomophila as the pathogen. The host populations were allowed either to evolve against a nonevolving pathogen or tocoevolve with the same pathogen. It was found that the coevolving hosts on average evolved higher survivorship against the coevolving pathogen and ancestral (nonevolving) pathogen relative to the hosts evolving against a nonevolving pathogen. The coevolving pathogens evolved greater ability to induce host mortality even in nonlocal (novel) hosts compared to infection by an ancestral (nonevolving) pathogen. Thus, these results clearly show that the evolved traits in the host and the pathogen under coevolution can be different from one-sided adaptation. In addition, the results also show that the coevolving host-pathogen interactions can involve certain general mechanisms in the pathogen, leading to increased mortality induction in nonlocal or novel hosts (Ahlawat, 2021).

    Modular Evolution of the Drosophila Metabolome

    Comparative phylogenetic studies offer a powerful approach to study the evolution of complex traits. While much effort has been devoted to the evolution of the genome and to organismal phenotypes, until now relatively little work has been done on the evolution of the metabolome, despite the fact that it is composed of the basic structural and functional building blocks of all organisms. This study explored variation in metabolite levels across 50 million years of evolution in the genus Drosophila, employing a common garden design to measure the metabolome within and among 11 species of Drosophila. This study found that both sex and age have dramatic and evolutionarily conserved effects on the metabolome. This study also found substantial evidence that many metabolite pairs covary after phylogenetic correction, and that such metabolome coevolution is modular. Some of these modules are enriched for specific biochemical pathways and show different evolutionary trajectories, with some showing signs of stabilizing selection. Both observations suggest that functional relationships may ultimately cause such modularity. These coevolutionary patterns also differ between sexes and are affected by age. This study also explored the relevance of modular evolution to fitness by associating modules with lifespan variation measured in the same common garden. Several modules associated with lifespan were found, particularly in the metabolome of older flies. Oxaloacetate levels in older females appear to coevolve with lifespan, and a lifespan-associated module in older females suggests that metabolic associations could underlie 50 million years of lifespan evolution (Harrison, 2021).

    Evolutionary History of the Hymenoptera

    Hymenoptera (sawflies, wasps, ants, and bees) are one of four mega-diverse insect orders, comprising more than 153,000 described and possibly up to one million undescribed extant species. As parasitoids, predators, and pollinators, Hymenoptera play a fundamental role in virtually all terrestrial ecosystems and are of substantial economic importance. To understand the diversification and key evolutionary transitions of Hymenoptera, most notably from phytophagy to parasitoidism and predation (and vice versa) and from solitary to eusocial life, this study inferred the phylogeny and divergence times of all major lineages of Hymenoptera by analyzing 3,256 protein-coding genes in 173 insect species. These analyses suggest that extant Hymenoptera started to diversify around 281 million years ago (mya). The primarily ectophytophagous sawflies are found to be monophyletic. The species-rich lineages of parasitoid wasps constitute a monophyletic group as well. The little-known, species-poor Trigonaloidea are identified as the sister group of the stinging wasps (Aculeata). Finally, the evolutionary root of bees were located within the apoid wasp family "Crabronidae." These results reveal that the extant sawfly diversity is largely the result of a previously unrecognized major radiation of phytophagous Hymenoptera that did not lead to wood-dwelling and parasitoidism. They also confirm that all primarily parasitoid wasps are descendants of a single endophytic parasitoid ancestor that lived around 247 mya. These findings provide the basis for a natural classification of Hymenoptera and allow for future comparative analyses of Hymenoptera, including their genomes, morphology, venoms, and parasitoid and eusocial life styles (Peters, 2017).

    Phylogeography of the Subgenus Drosophila (Diptera: Drosophilidae): Evolutionary history of faunal divergence between the old and the new worlds

    The current subgenus Drosophila (the traditional immigrans-tripunctata radiation) includes major elements of temperate drosophilid faunas in the northern hemisphere. Despite previous molecular phylogenetic analyses, the phylogeny of the subgenus Drosophila has not fully been resolved: the resulting trees have more or less varied in topology. One possible factor for such ambiguous results is taxon-sampling that has been biased towards New World species in previous studies. In this study, taxon sampling was balanced between Old and New World species, and phylogenetic relationships among 45 ingroup species selected from ten core species groups of the subgenus Drosophila were analyzed using nucleotide sequences of three nuclear and two mitochondrial genes. Based on the resulting phylogenetic tree, ancestral distributions and divergence times were estimated for each clade to test Throckmorton's hypothesis that there was a primary, early-Oligocene disjunction of tropical faunas and a subsequent mid-Miocene disjunction of temperate faunas between the Old and the New Worlds that occurred in parallel in separate lineages of the Drosophilidae. The results of this study substantially support Throckmorton's hypothesis of ancestral migrations via the Bering Land Bridge mainly from the Old to the New World, and subsequent vicariant divergence of descendants between the two Worlds occurred in parallel among different lineages of the subgenus Drosophila. However, the results also indicate that these events took place multiple times over a wider time range than Throckmorton proposed, from the late Oligocene to the Pliocene (Izumitani, 2016).

    Adaptive protein divergence of BMP ligands takes place under developmental and evolutionary constraints

    The bone morphogenetic protein (BMP) signaling network, comprising evolutionary conserved BMP2/4/Decapentaplegic (Dpp) and Chordin/Short gastrulation (Sog), is widely utilized for dorsal-ventral (DV) patterning during animal development. A similar network is required for posterior crossvein (PCV) formation in the Drosophila pupal wing. Although both transcriptional and post-transcriptional regulation of co-factors in the network appears to give rise to tissue-specific and species-specific properties, their mechanisms are incompletely understood. In Drosophila, BMP5-8 type ligands, Screw (Scw) and /aGlass bottom boat (Gbb), form heterodimers with Dpp for DV patterning and PCV development, respectively. Sequence analysis indicates that the Scw ligand contains two N-glycosylation motifs; one being highly conserved between BMP2/4 and BMP5-8 type ligands, and the other being Scw ligand-specific. The data reveal that N-glycosylation of the Scw ligand boosts BMP signaling both in cell culture and in the embryo. In contrast, N-glycosylation modifications of Gbb or Scw ligands reduce the consistency of PCV development. These results suggest that tolerance for structural changes of BMP5-8 type ligands is dependent on developmental constraints. Furthermore, gain and loss of N-glycosylation motifs in conserved signaling molecules under evolutionary constraints appear to constitute flexible modules to adapt to developmental processes (Tauscher, 2016).

    Genomics of parallel adaptation at two timescales in Drosophila

    Two interesting unanswered questions are the extent to which both the broad patterns and genetic details of adaptive divergence are repeatable across species, and the timescales over which parallel adaptation may be observed. Drosophila melanogaster is a key model system for population and evolutionary genomics. Findings from genetics and genomics suggest that recent adaptation to latitudinal environmental variation (on the timescale of hundreds or thousands of years) associated with Out-of-Africa colonization plays an important role in maintaining biological variation in the species. Additionally, studies of interspecific differences between D. melanogaster and its sister species D. simulans have revealed that a substantial proportion of proteins and amino acid residues exhibit adaptive divergence on a roughly few million years long timescale. This study used population genomic approaches to attack the problem of parallelism between D. melanogaster and a highly diverged conger, D. hydei, on two timescales. D. hydei, a member of the repleta group of Drosophila, is similar to D. melanogaster, in that it too appears to be a recently cosmopolitan species and recent colonizer of high latitude environments. Parallelism was observed both for genes exhibiting latitudinal allele frequency differentiation within species and for genes exhibiting recurrent adaptive protein divergence between species. Greater parallelism was observed for long-term adaptive protein evolution and this parallelism includes not only the specific genes/proteins that exhibit adaptive evolution, but extends even to the magnitudes of the selective effects on interspecific protein differences. Thus, despite the roughly 50 million years of time separating D. melanogaster and D. hydei, and despite their considerably divergent biology, they exhibit substantial parallelism, suggesting the existence of a fundamental predictability of adaptive evolution in the genus (Zhao, 2017).

    Inferring the distribution of selective effects from a time inhomogeneous model

    A Poisson random field model has been developed for estimating the distribution of selective effects of newly arisen nonsynonymous mutations that could be observed as polymorphism or divergence in samples of two related species under the assumption that the two species populations are not at mutation-selection-drift equilibrium. The model is applied to 91 Drosophila genes by comparing levels of polymorphism in an African population of D. melanogaster with divergence to a reference strain of D. simulans. Based on the difference of gene expression level between testes and ovaries, the 91 genes were classified as 33 male-biased, 28 female-biased, and 30 sex-unbiased genes. Under a Bayesian framework, Markov chain Monte Carlo simulations are implemented to the model in which the distribution of selective effects is assumed to be Gaussian with a mean that may differ from one gene to the other to sample key parameters. Based on estimates, the majority of newly-arisen nonsynonymous mutations that could contribute to polymorphism or divergence in Drosophila species are mildly deleterious with a mean scaled selection coefficient of -2.81, while almost 86% of the fixed differences between species are driven by positive selection. There are only 16.6% of the nonsynonymous mutations observed in sex-unbiased genes that are under positive selection in comparison to 30% of male-biased and 46% of female-biased genes that are beneficial. It was also estimated that D. melanogaster and D. simulans may have diverged 1.72 million years ago (Amei, 2019).

    Contrasting patterns of molecular evolution in metazoan germ line genes

    Germ lines are the cell lineages that give rise to the sperm and eggs in animals. The germ lines first arise from primordial germ cells (PGCs) during embryogenesis: these form from either a presumed derived mode of preformed germ plasm (inheritance) or from an ancestral mechanism of inductive cell-cell signalling (induction). Numerous genes involved in germ line specification and development have been identified and functionally studied. However, little is known about the molecular evolutionary dynamics of germ line genes in metazoan model systems. This study examined the molecular evolution of germ line genes within three metazoan model systems. These include the genus Drosophila (N=34 genes, inheritance), the fellow insect Apis (N=30, induction), and their more distant relative Caenorhabditis (N=23, inheritance). Using multiple species and established phylogenies in each genus, this study reports that germ line genes exhibited marked variation in the constraint on protein sequence divergence (dN/dS) and codon usage bias (CUB) within each genus. Importantly, it was found that de novo lineage-specific inheritance (LSI) genes in Drosophila (osk, pgc) and in Caenorhabditis (pie-1, pgl-1), which are essential to germ plasm functions under the derived inheritance mode, displayed rapid protein sequence divergence relative to the other germ line genes within each respective genus. This may reflect the evolution of specialized germ plasm functions and/or low pleiotropy of LSI genes, features not shared with other germ line genes. In addition, it was observed that the relative ranking of dN/dS and of CUB between genera were each more strongly correlated between Drosophila and Caenorhabditis, from different phyla, than between Drosophila and its insect relative Apis, suggesting taxonomic differences in how germ line genes have evolved. Taken together, the present results advance understanding of the evolution of animal germ line genes within three well-known metazoan models. Further, the findings provide insights to the molecular evolution of germ line genes with respect to LSI status, pleiotropy, adaptive evolution as well as PGC-specification mode (Whittle, 2019a).

    Evolution of salivary glue genes in Drosophila species

    At the very end of the larval stage Drosophila expectorate a glue secreted by their salivary glands to attach themselves to a substrate while pupariating. The glue is a mixture of apparently unrelated proteins, some of which are highly glycosylated and possess internal repeats. Because species adhere to distinct substrates (i.e. leaves, wood, rotten fruits), glue genes are expected to evolve rapidly. Available genome sequences and PCR-sequencing of regions of interest were used to investigate the glue genes in 20 Drosophila species. A new gene in addition was discovered to the seven glue genes annotated in D. melanogaster. A phase 1 intron was identified at a conserved position present in five of the eight glue genes of D. melanogaster, suggesting a common origin for those glue genes. A slightly significant rate of gene turnover was inferred. Both the number of repeats and the repeat sequence were found to diverge rapidly, even between closely related species. High repeat number variation was also detected at the intrapopulation level in D. melanogaster. It is concluded that most conspicuous signs of accelerated evolution are found in the repeat regions of several glue genes (Da Lage, 2019).

    Phylogenetic position of the Drosophila fima and dentissima lineages, and the status of the D. melanogaster species group

    The subgenus Sophophora of Drosophila, which includes D. melanogaster, is an important model for the study of molecular evolution, comparative genomics, and evolutionary developmental biology. Numerous phylogenetic studies have examined species relationships in the well-known melanogaster, obscura, willistoni, and saltans species groups, as well as the relationships among these clades. In contrast, other species groups of Sophophora have been relatively neglected and have not been subjected to molecular phylogenetic analysis. This study focuses on the endemic African Drosophila fima and dentissima lineages. Both these clades fall within the broadly defined melanogaster species group, but are otherwise distantly related to each other. The new phylogeny supports pervasive divergent and convergent evolution of male-specific grasping structures (sex combs). The implications of these results are discussed for defining the boundaries of the melanogaster species group, and weigh the relative merits of "splitting" and "lumping" approaches to the taxonomy of this key model system (Kopp, 2019).

    A phylogeny for the Drosophila montium species group: a model clade for comparative analyses

    The Drosophila montium species group is a clade of 94 named species closely related to the model species D. melanogaster. The montium species group is distributed over a broad geographic range throughout Asia, Africa, and Australasia. Species of this group possess a wide range of morphologies, mating behaviors, and endosymbiont associations, making this clade useful for comparative analyses. This study used genomic data from 42 available species to estimate the phylogeny and relative divergence times within the montium species group, and its relative divergence time from D. melanogaster. To assess the robustness of the phylogenetic inferences, three non-overlapping sets of 20 single-copy coding sequences were used, and all 60 genes were analyzed with both Bayesian and maximum likelihood methods. This analyses support monophyly of the group. Apart from the uncertain placement of a single species, D. baimaii, this analyses also support the monophyly of all seven subgroups proposed within the montium group. Phylograms and relative chronograms provide a highly resolved species tree, with discordance restricted to estimates of relatively short branches deep in the tree. In contrast, age estimates for the montium crown group, relative to its divergence from D. melanogaster, depend critically on prior assumptions concerning variation in rates of molecular evolution across branches, and hence have not been reliably determined. Methodological issues are discussed that limit phylogenetic resolution - even when complete genome sequences are available - as well as the utility of the current phylogeny for understanding the evolutionary and biogeographic history of this clade (Conner, 2020).

    How phenotypic convergence arises in experimental evolution

    Evolutionary convergence is a core issue in the study of adaptive evolution, as well as a highly debated topic at present. Few studies have analyzed this issue using a 'real-time' or evolutionary trajectory approach. Do populations that are initially differentiated converge to a similar adaptive state when experiencing a common novel environment? Drosophila subobscura populations founded from different locations and years showed initial differences and variation in evolutionary rates in several traits during short-term (approximately 20 generations) laboratory adaptation. This study has extended that analysis to 40 more generations to analyze (1) how differences in evolutionary dynamics among populations change between shorter and longer time spans, and (2) whether evolutionary convergence occurs after 60 generations of evolution in a common environment. Substantial variation was found in longer term evolutionary trajectories and differences between short- and longer term evolutionary dynamics. Although pervasive patterns of convergence were observed toward the character values of long-established populations, populations still remain differentiated for several traits at the final generations analyzed. This pattern might involve transient divergence, as is reported in some cases, indicating that more generations should lead to final convergence. These findings highlight the importance of longer term studies for understanding convergent evolution (Simoes, 2019).

    Polymorphism and Divergence of Novel Gene Expression Patterns in Drosophila melanogaster

    Transcriptomes may evolve by multiple mechanisms, including the evolution of novel genes, the evolution of transcript abundance, and the evolution of cell, tissue, or organ expression patterns. This study focused on the last of these mechanisms in an investigation of tissue and organ shifts in gene expression in Drosophila melanogaster. In contrast to most investigations of expression evolution, this study sought to provide a framework for understanding the mechanisms of novel expression patterns on a short population genetic timescale. To do so population samples of D. melanogaster transcriptomes were generated from five tissues: accessory gland, testis, larval salivary gland, female head, and first instar larva. These data were combined with comparable data from two outgroups to characterize gains and losses of expression, both polymorphic and fixed, in D. melanogaster. A large number of gain or loss of expression phenotypes were observed, most of which were polymorphic within D. melanogaster. Several polymorphic, novel expression phenotypes were strongly influenced by segregating cis-acting variants. In support of previous literature on the evolution of novelties functioning in male reproduction, many more novel expression phenotypes were found in the testis and accessory gland than in other tissues. Additionally, genes showing novel expression phenotypes tend to exhibit greater tissue specific expression. Finally, in addition to qualitatively novel expression phenotypes, genes exhibiting major quantitative expression divergence in the D. melanogaster lineage were identified (Cridland, 2020).

    Interspecific introgression reveals a role of male genital morphology during the evolution of reproductive isolation in Drosophila

    Rapid divergence in genital structures among nascent species has been posited to be an early-evolving cause of reproductive isolation, although evidence supporting this idea as a widespread phenomenon remains mixed. Using a collection of interspecific introgression lines between two Drosophila species that diverged ∼240,000 years ago, this study tested the hypothesis that even modest divergence in genital morphology can result in substantial fitness losses. The reproductive consequences were studied of variation in the male epandrial posterior lobes between Drosophila mauritiana and D. sechellia; divergence in posterior lobe morphology has significant fitness costs on several pre-fertilization and post-copulatory reproductive measures. Males with divergent posterior lobe morphology also significantly reduced the life span of their mates. Interestingly, one of the consequences of genital divergence was decreased oviposition and fertilization, which suggests that a sensory bias for posterior lobe morphology could exist in females, and thus posterior lobe morphology may be the target of cryptic female choice in these species. These results provide evidence that divergence in genitalia can in fact give rise to substantial reproductive isolation early during species divergence, and they also reveal novel reproductive functions of the external male genitalia in Drosophila (Frazee, 2021).

    Soft Selective Sweep on Chemosensory Genes Correlates with Ancestral Preference for Toxic Noni in a Specialist Drosophila Population

    Understanding how organisms adapt to environmental changes is a major question in evolution and ecology. In particular, the role of ancestral variation in rapid adaptation remains unclear because its trace on genetic variation, known as soft selective sweep, is often hardly recognizable from genome-wide selection scans. This study investigate the evolution of chemosensory genes in Drosophila yakuba mayottensis, a specialist subspecies on toxic noni (Morinda citrifolia) fruits on the island of Mayotte. Population genomics analyses and behavioral assays were combined to evaluate the level of divergence in chemosensory genes and perception of noni chemicals between specialist and generalist subspecies of D. yakuba. A signal of soft selective sweep was identified on a handful of genes, with the most diverging ones involving a cluster of gustatory receptors expressed in bitter-sensing neurons. These results highlight the potential role of ancestral genetic variation in promoting host plant specialization in herbivorous insects and identify a number of candidate genes underlying behavioral adaptation (Ferreira, 2020).

    Detection of hard and soft selective sweeps from Drosophila melanogaster population genomic data

    Whether hard sweeps or soft sweeps dominate adaptation has been a matter of much debate. Recently, haplotype homozygosity statistics were developed that (i) can detect both hard and soft sweeps with similar power and (ii) can classify the detected sweeps as hard or soft. The application of this method to population genomic data from a natural population of Drosophila melanogaster (DGRP) allowed rediscovery of three known cases of adaptation at the loci Ace, Cyp6g1, and CHKov1 known to be driven by soft sweeps, and additional candidate loci were detected for recent and strong sweeps. Surprisingly, all of the top 50 candidates showed patterns much more consistent with soft rather than hard sweeps. Recently, this work has been criticized by suggesting that all the candidate loci detected by the haplotype statistics, including the positive controls, are unlikely to be sweeps at all and that instead these haplotype patterns can be more easily explained by complex neutral demographic models. This criticism also claimed that these neutral non-sweeps are likely to be hard instead of soft sweeps. This study reanalyze the DGRP data using a range of complex admixture demographic models and reconfirmed the original published results suggesting that the majority of recent and strong sweeps in D. melanogaster are first likely to be true sweeps, and second, that they do appear to be soft. Furthermore, ways to take this work forward are discussed given that most demographic models employed in such analyses are necessarily too simple to capture the full demographic complexity, while more realistic models are unlikely to be inferred correctly because they require a large number of free parameters (Garud, 2021).

    Dominance shifts increase the likelihood of soft selective sweeps

    Genetic models of adaptation to a new environment have typically assumed that the alleles involved maintain a constant fitness dominance across the old and new environments. However, theories of dominance suggest that this should often not be the case. Instead, the alleles involved should frequently shift from recessive deleterious in the old environment to dominant beneficial in the new environment. This paper examines the consequences of these expected dominance shifts for the genetics of adaptation to a new environment. Dominance shifts were found to increase the likelihood that adaptation occurs from standing variation, and that multiple alleles from the standing variation are involved (a soft selective sweep). Furthermore, it was found that expected dominance shifts increase the haplotypic diversity of selective sweeps, rendering soft sweeps more detectable in small genomic samples. In cases where an environmental change threatens the viability of the population, it was shown that expected dominance shifts of newly beneficial alleles increase the likelihood of evolutionary rescue and the number of alleles involved. Finally, the results are applied to a well-studied case of adaptation to a new environment: the evolution of pesticide resistance at the Ace locus in Drosophila melanogaster. Under reasonable demographic assumptions, the expected dominance shift of resistant alleles causes soft sweeps to be the most frequent outcome in this case, with the primary source of these soft sweeps being the standing variation at the onset of pesticide use, rather than recurrent mutation thereafter (Muralidhar, 2022).

    Soft selective sweeps: Addressing new definitions, evaluating competing models, and interpreting empirical outliers

    The ability to accurately identify and quantify genetic signatures associated with soft selective sweeps based on patterns of nucleotide variation has remained controversial. This study provides counter viewpoints to recent publications in PLOS Genetics that have argued not only for the statistical identifiability of soft selective sweeps, but also for their pervasive evolutionary role in both Drosophila and HIV populations. Evidence is presented that these claims owe to a lack of consideration of competing evolutionary models, unjustified interpretations of empirical outliers, as well as to new definitions of the processes themselves. The results highlight the dangers of fitting evolutionary models based on hypothesized and episodic processes without properly first considering common processes and, more generally, of the tendency in certain research areas to view pervasive positive selection as a foregone conclusion (Johri, 2022).

    Allometry constrains the evolution of sexual dimorphism in Drosophila across 33 million years of divergence

    Sexual dimorphism is widely viewed as adaptive, reflecting the evolution of males and females towards divergent fitness optima. Its evolution, however, may often be constrained by the shared genetic architecture of the sexes, and by allometry. This study investigated the evolution of sexual size dimorphism, shape dimorphism, and their allometric relationship, in the wings of 82 taxa in the family Drosophilidae which have been diverging for at least 33 million years. Shape dimorphism among species was remarkably similar, with males characterized by longer thinner wings than females. There was, however, quantitative variation among species in both size and shape dimorphism, with evidence that they have adapted to different evolutionary optima in different clades on timescales of about 10 million years. Within species, shape dimorphism was predicted by size, and among species, there was a strong relationship between size dimorphism and shape dimorphism. Allometry constrained the evolution of shape dimorphism for the two most variable traits studied, but dimorphism was evolutionary labile in other traits. The keys for disentangling alternative explanations for dimorphism evolution are studies of natural and sexual selection, together with a deeper understanding of how microevolutionary parameters of evolvability relate to macroevolutionary patterns of divergence (Sztepanacz, 2021).

    Screens in fly and beetle reveal vastly divergent gene sets required for developmental processes

    Drosophila is a prime model for insect genetics, and while conservation of many gene functions has been observed among bilaterian animals, a plethora of data show evolutionary divergence of gene function among more closely-related groups, such as within the insects. A quantification of conservation versus divergence of gene functions has been missing, without which it is unclear how representative data from model systems actually are. This study systematically compare the gene sets required for a number of homologous but divergent developmental processes between fly and beetle in order to quantify the difference of the gene sets. To that end, the RNAi screen in the red flour beetle Tribolium castaneum was expanded to cover more than half of the protein-coding genes. The gene sets required for four different developmental processes between beetle and fly were compared. Around 50% of the gene functions were identified in the screens of both species while for the rest, phenotypes were revealed only in fly (~ 10%) or beetle (~ 40%) reflecting both technical and biological differences. Accordingly, it was possible to annotate novel developmental GO terms for 96 genes studied in this work. This paper is the final dataset for the pupal injection screen of the iBeetle screen reaching a coverage of 87% (13,020 genes). It is concluded that the gene sets required for a homologous process diverge more than widely believed. Hence, the insights gained in flies may be less representative for insects or protostomes than previously thought, and work in complementary model systems is required to gain a comprehensive picture. The RNAi screening resources developed in this project, the expanding transgenic toolkit, and our large-scale functional data make T. castaneum an excellent model system in that endeavor (Hakeemi, 2022).

    Expression of netrin and its receptors uncoordinated-5 and frazzled in arthropods and onychophorans suggests conserved and diverged functions in neuronal pathfinding and synaptogenesis

    Development of the nervous system and the correct connection of nerve cells require coordinated axonal pathfinding through an extracellular matrix. Outgrowing axons exhibit directional growth toward or away from external guidance cues such as Netrin. Guidance cues can be detected by growth cones that are located at the end of growing axons through membrane-bound receptors such as Uncoordinated-5 and Frazzled. Binding of Netrin causes reformation of the cytoskeleton and growth of the axon toward (or away from) the source of Netrin production. This study investigate the embryonic mRNA expression patterns of netrin genes and their potential receptors, uncoordinated-5 and frazzled in arthropod species that cover all main branches of Arthropoda, that is, Pancrustacea, Myriapoda, and Chelicerata. The expression patterns were also studied in a closely related outgroup species, the onychophoran Euperipatoides kanangrensis, and data is provided on expression profiles of these genes in larval tissues of the fly Drosophila melanogaster including the brain and the imaginal disks. These data reveal conserved and diverged aspects of neuronal guidance in Drosophila with respect to the other investigated species and suggest a conserved function in nervous system patterning of the developing appendages (Janssen, 2022).

    Desiccation resistance differences in Drosophila species can be largely explained by variations in cuticular hydrocarbons

    Maintaining water balance is a universal challenge for organisms living in terrestrial environments, especially for insects, which have essential roles in the ecosystem. Although the high surface area to volume ratio in insects makes them vulnerable to water loss, insects have evolved different levels of desiccation resistance to adapt to diverse environments. To withstand desiccation, insects use a lipid layer called cuticular hydrocarbons (CHCs) to reduce water evaporation from the body surface. It has long been hypothesized that the water-proofing capability of this CHC layer, which can confer different levels of desiccation resistance, depends on its chemical composition. However, it is unknown which CHC components are important contributors to desiccation resistance and how these components can determine differences in desiccation resistance. In this study, machine-learning algorithms, correlation analyses, and synthetic CHCs were used to investigate how different CHC components affect desiccation resistance in 50 Drosophila and related species. Desiccation resistance differences across these species were shown to be largely explained by variation in CHC composition. In particular, length variation in a subset of CHCs, the methyl-branched CHCs (mbCHCs), is a key determinant of desiccation resistance. There is also a significant correlation between the evolution of longer mbCHCs and higher desiccation resistance in these species. Given that CHCs are almost ubiquitous in insects, it is suggested that evolutionary changes in insect CHC components can be a general mechanism for the evolution of desiccation resistance and adaptation to diverse and changing environments (Wang, 2022).

    Comparative morphology of serotonin-immunoreactive neurons innervating the central complex in the brain of dicondylian insects

    Serotonin (5-hydroxytryptamine) acts as a widespread neuromodulator in the nervous system of vertebrates and invertebrates. In insects, it promotes feeding, enhances olfactory sensitivity, modulates aggressive behavior, and, in the central complex of Drosophila, serves a role in sleep homeostasis. In addition to a role in sleep-wake regulation, the central complex has a prominent role in spatial orientation, goal-directed locomotion, and navigation vector memory. To further understand the role of serotonergic signaling in this brain area, this study analyzed the distribution and identity of serotonin-immunoreactive neurons across a wide range of insect species. While one bilateral pair of tangential neurons innervating the central body was present in all species studied, a second type was labeled in all neopterans but not in dragonflies and firebrats. Both cell types show conserved major fiber trajectories but taxon-specific differences in dendritic targets outside the central body and axonal terminals in the central body, noduli, and lateral accessory lobes. In addition, numerous tangential neurons of the protocerebral bridge were labeled in all studied polyneopteran species except for Phasmatodea, but not in Holometabola. Lepidoptera and Diptera showed additional labeling of two bilateral pairs of neurons of a third type. The presence of serotonin in systems of columnar neurons apparently evolved independently in dragonflies and desert locusts. The data suggest distinct evolutionary changes in the composition of serotonin-immunolabeled neurons of the central complex and provides a promising basis for a phylogenetic study in a wider range of arthropod species (Homberg, 2023).

    Functional Divergence of the Tribolium castaneum engrailed and invected Paralogs

    engrailed (en) and invected (inv) encode paralogous transcription factors found as a closely linked tandem duplication within holometabolous insects. Drosophila en mutants segment normally, then fail to maintain their segments. Loss of Drosophila inv is viable, while loss of both genes results in asegmental larvae. Surprisingly, the knockdown of Oncopeltus inv can result in the loss or fusion of the entire abdomen and en knockdowns in Tribolium show variable degrees of segmental loss. The consequence of losing or knocking down both paralogs on embryogenesis has not been studied beyond Drosophila. To further investigate the relative functions of each paralog and the mechanism behind the segmental loss, Tribolium double and single knockdowns of en and inv were analyzed. The most common cuticular phenotype of the double knockdowns was small, limbless, and open dorsally, with all but a single, segmentally iterated row of bristles. Less severe knockdowns had fused segments and reduced appendages. The Tribolium paralogs appear to act synergistically: the knockdown of either Tribolium gene alone was typically less severe, with all limbs present, whereas the most extreme single knockdowns mimic the most severe double knockdown phenotype. Morphological abnormalities unique to either single gene knockdown were not found. inv expression was not affected in the Tribolium en knockdowns, but hh expression was unexpectedly increased midway through development. Thus, while the segmental expression of en/inv is broadly conserved within insects, the functions of en and inv are evolving independently in different lineages (Blunk, 2023).

    A full repertoire of Hemiptera genomes reveals a multi-step evolutionary trajectory of auto-RNA editing site in insect Adar gene

    Adenosine-to-inosine (A-to-I) RNA editing, mediated by metazoan ADAR enzymes, is a prevalent post-transcriptional modification that diversifies the proteome and promotes adaptive evolution of organisms. The Drosophila Adar gene has an auto-recoding site (termed S>G site) that forms a negative-feedback loop and stabilizes the global editing activity. However, the evolutionary trajectory of Adar S>G site in many other insects remains largely unknown, preventing a deeper understanding on the significance of this auto-editing mechanism. This study retrieved the well-annotated genomes of 375 arthropod species including the five major insect orders (Lepidoptera, Diptera, Coleoptera, Hymenoptera and Hemiptera) and several outgroup species. Comparative genomic analysis was performed on the Adar auto-recoding S>G site. The ancestral state of insect S>G site was found to be an uneditable serine codon (unSer); this state was largely maintained in Hymenoptera. The editable serine codon (edSer) appeared in the common ancestor of Lepidoptera, Diptera and Coleoptera and was almost fixed in the three orders. Interestingly, Hemiptera species possessed comparable numbers of unSer and edSer codons, and a few 'intermediate codons', demonstrating a multi-step evolutionary trace from unSer-to-edSer with non-synchronized mutations at three codon positions. It is argued that the evolution of Adar S>G site is the best genomic evidence supporting the 'proteomic diversifying hypothesis' of RNA editing. This work deepens our understanding on the evolutionary significance of Adar auto-recoding site which stabilizes the global editing activity and controls transcriptomic diversity (Ma, 2023)

    A single-cell transcriptomic atlas tracking the neural basis of division of labour in an ant superorganism

    Ant colonies with permanent division of labour between castes and highly distinct roles of the sexes have been conceptualized to be superorganisms, but the cellular and molecular mechanisms that mediate caste/sex-specific behavioural specialization have remained obscure. This study characterized the brain cell repertoire of queens, gynes (virgin queens), workers and males of Monomorium pharaonis by obtaining 206,367 single-nucleus transcriptomes. In contrast to Drosophila, the mushroom body Kenyon cells are abundant in ants and display a high diversity with most subtypes being enriched in worker brains, the evolutionarily derived caste. Male brains are as specialized as worker brains but with opposite trends in cell composition with higher abundances of all optic lobe neuronal subtypes, while the composition of gyne and queen brains remained generalized, reminiscent of solitary ancestors. Role differentiation from virgin gynes to inseminated queens induces abundance changes in roughly 35% of cell types, indicating active neurogenesis and/or programmed cell death during this transition. Insemination-induced cell changes were identified probably associated with the longevity and fecundity of the reproductive caste, including increases of ensheathing glia and a population of dopamine-regulated Dh31-expressing neurons. It is concluded that permanent caste differentiation and extreme sex-differentiation induced major changes in the neural circuitry of ants (Li, 2022).

    This study generated a superorganismal brain cell atlas by profiling all brain cells of the full panel of adult phenotypes that typically make up an ant colony. The ant mushroom body KCs are abundant and transcriptionally diverse relative to the KCs of Drosophila. Conserved optic lobe (OL) neurons were identified that probably play crucial roles in visual courtship behaviour and circadian rhythm regulation in ants. The results are consistent with advanced brain-level division of labour in superorganismal colonies and shed new light on neural mechanisms associated with the lifespan differences between workers and queens (Li, 2022).

    It was expected that the major evolutionary transition to superorganismal colony organization in ancestral ants should have selected for specialization of neural circuitry rather than bigger brains per se. This study provides direct evidence to support this hypothesis, with high degrees of specialization being detectable in the brain cellular composition of all four adult phenotypes of M. pharaonis ants. 41 out of 43 cell types could be detected in all four brain phenotypes, albeit in different abundances. In particular, workers and males have evolved extreme forms of brain specialization and with almost opposite cell-type preferences. Worker brains had the most abundant KCs and optic nerves (OPNs) and the least abundant optic lobe (OL) neurons, all biases that were opposite in male brains. These cellular differences were consistent with anatomical brain structures reflecting the distinct social and sexual specialization in these two phenotypes. Males are extremely short-lived and do not take part in any colony maintenance tasks, as their only function is to find and inseminate a virgin queen. Ant males therefore function as 'simple minded' but extremely targeted sperm vectors. In sharp contrast, workers engage in all the colony tasks except reproduction and need multipurpose brains, consistent with the KCs and OPNs in workers being biased for processing complex information associated with nursing, foraging, colony defence and social communication (Li, 2022).

    Relative to these extremes, gynes and queens had intermediate abundances for almost all brain cell types. This probably reflects that both gynes and queens have maintained functional brain repertoires for a large subset of the social tasks normally done in more advanced ways by workers. Many ants may have retained generalist queen brain functions because they have solitary lives during colony founding, so they need to nurse a first brood and in some species even to forage. However, finding relatively generalist brains in M. pharaonis gynes and queens is remarkable because this species has lost that ancestral independent colony founding behaviour and never needs to operate without worker assistance. However, Monomorium colonies have very many queens, some of which may fail to become inseminated. Such failed queens are known to survive, albeit for less time than inseminated queens, and perform worker-like behaviours, which may have selected for the maintenance of general cognitive abilities in the gyne/queen caste (Li, 2022).

    Overall, the results confirm the concept of complementary divergence in brain function between superorganismal colony members and strongly suggest that fine-tuned brain-level division of labour is an integrated part of sex, caste and reproductive role differentiation, in ways that are not expected to evolve in social systems where a variable number of colony members retain breeder potential even though they may first have helper roles. In many ways, the separate individual brains in colonies of ants such as M. pharaonis combine into a modularly coordinated super-neural organization maintained by advanced communication between colony members. Individual brains are continuously turned over when adult colony members hatch and die, but functional homeostasis and balanced interactions between modules continue, similar to how cells in a metazoan body are turned over without compromising overall body health. The complementary functions of individual brains across the full panel of adult phenotypes are consistent with natural selection maximizing colony-level fitness, as expected for all superorganismal social insects, but not for animals that form societies without irreversible caste differentiation for life among all colony members (Li, 2022).

    Gynes and queens represent two subsequent functional states of the same reproductive female caste, separated by a single insemination event that induces substantial brain transcriptome remodelling resulting in remarkable shifts in behaviour. The gene regulatory network that mediates this reproductive role differentiation is insemination-specific rather than queen-specific, because it has been co-opted by distantly related ant species that secondarily shifted to reproduction via worker-gamergates rather than queens. The present study further explored this convergent evolutionary scenario across castes at the brain cell level. There are parallel cellular shifts across these two caste-specific reproductive role transitions induced by insemination. In particular, a cluster of ensheathing glia with neuroprotective and anti-ageing functions was expanded in both M. pharaonis queens and H. saltator gamergates. It is therefore speculated that ensheathing glia modification might represent one of the proximate mechanisms that ancestrally prolonged queen longevity in ants and whose co-option secondarily extended worker lifespan when they became inseminated as gamergate reproductives. This quantitative reinforcement mechanism of particular neural modules in adulthood effectively decouples queen and worker ageing, so that extremely divergent caste-specific lifespans could evolve (Li, 2022).

    Insemination also induced the expansion of dopamine neurons and a cluster of downstream Dop2R expressing neurons in M. pharaonis queens, and the counterpart cell cluster in H. saltator was found to be convergently expanded in gamergates as well. Experimental confirmation of the gonadotrophic function of dopamine via feeding M. pharaonis gynes with l-dopa suggests that dormant ovary maturation in gynes may be switched into an accelerating trajectory by elevating functionality of dopamine neurons. The downstream Dop2R neurons also preferentially expressed Dh31, a diuretic hormone known to regulate ovulation in flies. The simultaneously expanded dopamine neurons and downstream Dop2R neurons may thus constitute an integral and conserved neural module to realize enhanced reproductive potential in ant queens well beyond the normal fertility levels of solitary insects (Li, 2022).

    Accelerated inbreeding depression suggests synergistic epistasis for deleterious mutations in Drosophila melanogaster

    Synergistic epistasis for deleterious alleles is relevant to the mutation load paradox and the evolution of sex and recombination. Some studies have shown evidence of synergistic epistasis for spontaneous or induced deleterious mutations appearing in mutation-accumulation experiments. However, many newly arising mutations may not actually be segregating in natural populations because of the erasing action of natural selection. A demonstration of synergistic epistasis for naturally segregating alleles can be achieved by means of inbreeding depression studies, as deleterious recessive allelic effects are exposed in inbred lines. This paper reports the results of two independent inbreeding experiments carried out with two different populations of Drosophila melanogaster. The results show a consistent accelerated inbreeding depression for fitness, suggesting synergistic epistasis among deleterious alleles. Computer simulations were performed assuming different possible models of epistasis and mutational parameters for fitness, finding some of them to be compatible with the results observed. These results suggest that synergistic epistasis for deleterious mutations not only occurs among newly arisen spontaneous or induced mutations, but also among segregating alleles in natural populations (Dominguez-Garcia, 2019).

    Adaptive substitutions underlying cardiac glycoside insensitivity in insects exhibit epistasis in vivo

    Predicting how species will respond to selection pressures requires understanding the factors that constrain their evolution. This study used genome engineering of Drosophila to investigate constraints on the repeated evolution of unrelated herbivorous insects to toxic cardiac glycosides, which primarily occurs via a small subset of possible functionally-relevant substitutions to Na(+),K(+)-ATPase. Surprisingly, frequently observed adaptive substitutions were found at at two sites, 111 and 122, are lethal when homozygous and adult heterozygotes exhibit dominant neural dysfunction. A phylogenetically correlated substitution, A119S, was found that partially ameliorates the deleterious effects of substitutions at 111 and 122. Despite contributing little to cardiac glycoside-insensitivity in vitro, A119S, like substitutions at 111 and 122, substantially increases adult survivorship upon cardiac glycoside exposure. These results demonstrate the importance of epistasis in constraining adaptive paths. Moreover, by revealing distinct effects of substitutions in vitro and in vivo, the results underscore the importance of evaluating the fitness of adaptive substitutions and their interactions in whole organisms (Taverner, 2019).

    Epistatic selection on a selfish Segregation Distorter supergene - drive, recombination, and genetic load

    Meiotic drive supergenes are complexes of alleles at linked loci that together subvert Mendelian segregation resulting in preferential transmission. In males, the most common mechanism of drive involves the disruption of sperm bearing one of a pair of alternative alleles. While at least two loci are important for male drive-the driver and the target-linked modifiers can enhance drive, creating selection pressure to suppress recombination. This work investigates the evolution and genomic consequences of an autosomal, multilocus, male meiotic drive system, Segregation Distorter (SD) in the fruit fly, Drosophila melanogaster. In African populations, the predominant SD chromosome variant, SD-Mal, is characterized by two overlapping, paracentric inversions on chromosome arm 2R and nearly perfect (~100%) transmission. The SD-Mal system in was studied in detail, exploring its components, chromosomal structure, and evolutionary history. The findings reveal a recent chromosome-scale selective sweep mediated by strong epistatic selection for haplotypes carrying Sd, the main driving allele, and one or more factors within the double inversion. While most SD-Mal chromosomes are homozygous lethal, SD-Mal haplotypes can recombine with other, complementing haplotypes via crossing over, and with wildtype chromosomes via gene conversion. SD-Mal chromosomes have nevertheless accumulated lethal mutations, excess non-synonymous mutations, and excess transposable element insertions. Therefore, SD-Mal haplotypes evolve as a small, semi-isolated subpopulation with a history of strong selection. These results may explain the evolutionary turnover of SD haplotypes in different populations around the world and have implications for supergene evolution broadly (Navarro-Dominguez, 2022).

    The ability of Drosophila hybrids to locate food declines with parental divergence

    Hybrids are generally less fit than their parental species, and the mechanisms underlying their fitness reductions can manifest through different traits. For example, hybrids can have physiological, behavioral, or ecological defects, and these defects can generate reproductive isolation between their parental species. However, the rate that mechanisms of postzygotic isolation other than hybrid sterility and inviability evolve has remained largely uninvestigated, despite isolated studies showing that behavioral defects in hybrids are not only possible but might be widespread.This work studied a fundamental animal behavior - the ability of individuals to find food - and tested the rate at which it breaks down in hybrids. The ability of hybrids from 94 pairs of Drosophila species to find food was measured, and this ability was shown to decrease with increasing genetic divergence between the parental species and that male hybrids are more strongly (and negatively) affected than females. These findings quantify the rate that hybrid dysfunction evolves across the diverse radiation of Drosophila and highlights the need for future investigations of the genetic and neurological mechanisms that affect a hybrid's ability to find a suitable substrate on which to feed and breed (Turissini, 2017).

    The Drosophila speciation factor HMR localizes to genomic insulator sites

    Hybrid incompatibility between Drosophila melanogaster and D. simulans is caused by a lethal interaction of the proteins encoded by the Hmr (Hybrid male rescue) and Lhr (Lethal hybrid rescue) genes. In D. melanogaster the loss of HMR results in mitotic defects, an increase in transcription of transposable elements and a deregulation of heterochromatic genes. To better understand the molecular mechanisms that mediate HMR's function, this study measured genome-wide localization of HMR in D. melanogaster tissue culture cells by chromatin immunoprecipitation. Interestingly, HMR was found to localize to genomic insulator sites that can be classified into two groups. One group belongs to gypsy insulators and another one borders HP1a bound regions at active genes. The transcription of the latter group genes is strongly affected in larvae and ovaries of Hmr mutant flies. These data suggest a novel link between HMR and insulator proteins, a finding that implicates a potential role for genome organization in the formation of species (Gerland, 2017).

    Biodiversity is the result of the emergence and the extinction of species. New species form by pre- and post-zygotic isolation mediated by genetic incompatibility. One of the best characterized examples of hybrid incompatibility is the gene pair Hybrid male rescue (Hmr) and Lethal hybrid rescue (Lhr). Hmr and Lhr cause hybrid incompatibility between the closely related fly species Drosophila melanogaster and D. simulans. Hmr diverged in both Drosophila sibling species under positive selection. HMR and LHR from both species interact physically and localize predominantly to centromeric regions. A reduction of HMR expression results in a misregulation of transposable elements, satellite DNAs and heterochromatic genes. The major difference between HMR and LHR in D. melanogaster and D. simulans is their substantial difference in protein amounts which has been proposed to result in a lethal gain of function in male hybrids. High levels of HMR and LHR in hybrids and overexpression of these proteins in pure species lead to an increased number of binding sites of the complex. Such spreading phenomena based on protein amount have been observed for several chromatin-associated complexes such as the dosage compensation complex, the polycomb complex or components of pericentromeric heterochromatin. In most cases, the precise mechanisms for targeting and spreading are not fully understood. Interestingly, several of the components involved in these processes show signs of adaptive evolution and differ substantially even in very closely related organisms. This observation has spurred a model of a dynamic genome that drives the adaptive evolution of chromatin-associated factors (Gerland, 2017 and references therein).

    Eukaryotic genomes of closely related species differ mostly in the amount and sequence of repetitive DNA. This DNA is often derived from transposable elements, which are highly mutagenic and are therefore under tight transcriptional control by the cellular machinery. During evolution transposons or transposon-derived sequences occasionally adopted structural or novel cis-regulatory functions, thereby contributing to the evolution of new, species-specific, phenotypic traits. Genomic insulators are a particular class of such novel, fast evolving, cis-regulatory elements that show signs of transposon ancestry. A strong expansion of these elements is observed in arthropods, which also experienced a successive gain in the number of insulator binding proteins during evolution. In fact, the Drosophila genome harbours a large variety of insulator proteins such as CTCF, BEAF-32, Su(Hw), Mod(mdg4) and CP190, which all affect nuclear architecture. Different Drosophila species underwent multiple genomic rearrangements and transposon invasions, which presumably resulted in an adaptive response of regulatory DNA binding factors to maintain spatial and temporal gene expression. For example, binding sites for the insulator proteins BEAF-32 and CTCF show a high degree of variability when compared among very closely related species. The gain of new insulator sites is associated with chromosome rearrangements, new born genes and species-specific transcription regulation. Similar to insulator proteins, which tend to cluster in specific nuclear regions, the speciation factor HMR clusters at centromeres or pericentromeric regions in diploid cells but is also detected at distinct euchromatic regions along the chromosome arms in polytene chromosomes. A unifying feature for many of these sites is their close proximity to binding sits of the Heterochromatin Protein 1 (HP1a), a HMR interactor and a well-characterized heterochromatic mark (Gerland, 2017).

    Various studies describe HMR's localization to heterochromatin, but the molecular details on HMR's binding sites and its recruitment to these sites are not well understood. To get new insights into HMR's association to chromatin, this study measured HMR's genome-wide localization by chromatin immunoprecipitation (ChIP) in the D. melanogaster embryonic S2 cell line. This analysis demonstrated an extensive colocalization of HMR with a subset of insulator sites across the genome. HMR's binding to genomic gypsy insulators, which constitute the major group of its binding sites, is dependent on the residing insulator protein complex. In a second group, HMR borders heterochromatin together with the insulator protein BEAF-32. In agreement with previous low-resolution techniques in cell lines and fly tissue, these binding sites are enriched at pericentromeric regions, the cytological region 31 on the 2nd chromosome and the entire 4th chromosome. At most of these sites, HMR associates to the promoters of actively transcribed genes. Interestingly, these genes code for transcripts that have been reported to be downregulated in Hmr mutant larvae and ovaries. Altogether, these data provide evidence for a functional link between HMR and insulator proteins, which potentially results in hybrid incompatibilities due to the adaptive evolution of these genome-organizing complexes (Gerland, 2017).

    HMR localizes to centromeric and pericentromeric regions in D. melanogaster cell lines as well as in mitotically dividing embryonic cells where it has been suggested to act as a repressor of transposable elements. Mutations in Hmr lead to overexpression of satellite DNA and transposable elements in ovaries and larvae. Such a derepression is also observed in hybrid flies, where HMR and LHR levels are higher than the ones in pure species and result in a widespread distribution of the HMR/LHR complex. To better understand the targeting principles that mediate HMR binding within the D. melanogaster genome, it was asked whether it is possible to identify HMR binding sites by applying ChIP-Seq in the D. melanogaster S2 cell line. Combining this approach with RNAi mediated knockdown experiments this study uncovered a strong colocalization of HMR with gypsy insulator binding sites and demonstrated that HMR binding to these sites depends on the presence of the residing insulator protein complex. Notably, HMR associates only with a subset of all Su(Hw) binding sites, but almost all those sites can be classified as gypsy-like sites bound by CP190 and mod(mdg4) in addition to Su(Hw) (Gerland, 2017).

    Besides dispersed binding of HMR at genomic gypsy insulator sites along the chromosome arms, dense clusters of HMR binding sites were observed around the centromere and on the 4th chromosome where it potentially serves to separate HP1a binding domains from highly active genes. This dense clustering of binding sites around the centromere correlates well with the strong colocalization of HMR signals with the centromeric H3 variant CID in immunolocalization experiments. Due to its biochemical interaction and partial colocalization with the heterochromatin protein HP1a in Drosophila embryos, HMR has been suggested to be a bona-fide heterochromatin component. However, in contrast to HP1a, this study detected very distinct HMR binding sites within the genome. When HMR is found close to an HP1a binding domain, it rather borders it than covering the whole domain. The sharp HMR binding signals and the fact that almost all euchromatic HMR binding sites contain putative insulator elements, suggest a role of HMR in separating chromatin domains. A distinct boundary that separates constitutive heterochromatin from the core centromere has also been postulated by Olszak and colleagues who suggest that transition zones between heterochromatin and euchromatin are hotspots for sites of CID misincorporation. Unfortunately, centromeres are notoriously difficult to study by next generation sequencing due to their highly repetitive nature. In addition, the microscopic resolution is not sufficiently high to allow a distinction between a binding to the core centromere chromatin and the chromatin immediately adjacent to it. Therefore, it cannot be ruled that HMR binds large domains at the central region of the Drosophila centromere. However, the fact that the purification of chromatin containing the centromeric H3 variant CID did not identify HMR, suggests that it may very well also form a boundary between pericentromeric heterochromatin and the core centromere. To which extent and by which mechanism HMR fulfils a functional role at these genomic sites remains to be elucidated (Gerland, 2017).

    The genomic sites, where HMR was found bound next to an HP1a domain, are highly enriched for recognition sites of the insulator protein BEAF-32. Interestingly, a depletion of BEAF-32 in S2 cells results in an increased rate of mitotic defects, which is very reminiscent of the phenotype detected when HMR is depleted. Similarly to flies carrying a mutation in the Hmr gene, flies in which BEAF-32 is only contributed maternally have defects in female fertility. BEAF-32's role in maintaining associated promoter regions in an environment that facilitates high transcription levels has been suggested to be functionally relevant for this phenotype. Strikingly, this study found most HMR/BEAF-32 binding sites located between HP1a containing heterochromatin and the transcription start site of a highly active gene. HP1a chromatin might fulfil a repressive function at these genomic regions and HMR might block this repressive impact on the neighbouring gene body. However, no extensive spreading of HP1a or H3K9me3 is seen upon HMR knockdown suggesting that the repressive effect is not directly mediated by HP1a binding or the HMR knock down not efficient enough. As there is evidence that HP1a can also promote gene transcription, HMR may also function as a co-activator for HP1a. Currently, HMR binding next to HP1a containing chromatin is considered as a unifying feature of transcriptionally affected genes but the potential mechanism by which HMR exerts its function is as yet unknown (Gerland, 2017).

    Although HMR depletion has a substantial effect on the transcription of multiple transposons, HMR was found enriched only at the 5' insulator region of the gypsy or gtwin retrotransposons and to similar sites within the genome that are presumably derived from these elements. These sites are occupied by insulator proteins Su(Hw), CP190 and Mod(mdg4) and often display enhancer blocking activity in transgenic assays. Artificial targeting of HMR to DNA placed between an enhancer and a promoter of a reporter gene can block the transcription activity, suggesting that HMR may indeed play a role in setting up endogenous boundary elements. Similar to what is known for Su(Hw), HMR binding to this class of binding sites is dependent on the presence of the structural protein CP190, which has a key function in the stabilization of insulator protein complexes. However, as no strong physical interaction is observed between CP190 and HMR, the loss of HMR binding upon a reduction of CP190 levels may also be the result of increased nucleosome occupancy. Such increase in Histone H3 binding cannot be observed upon HMR removal suggesting that HMR acts downstream of CP190. Interestingly, CP190 loss impairs HMR binding to gypsy-like insulator sites but has weak effect on HMR binding to sites containing BEAF-32 recognition motifs. Notably, in contrast to BEAF-32, CP190 is not required for oogenesis, suggesting that the lack of HMR binding to the class 1 sites may be responsible for the female sterility phenotype observed in Hmr mutant flies (Gerland, 2017).

    How can the current findings be integrated with the lethal phenotype of increased HMR/LHR levels in male hybrids? It is tempting to speculate that multiple additional binding sites that are observed in hybrids and on polytene chromosomes of fly strains over-expressing HMR constitute boundary regions. An increased binding to such boundaries, which have been shown to cluster and form aggregates in vivo, may trigger a massive change in nuclear architecture. In turn, this could indirectly activate multiple transposable elements similar to what is observed when centromere clustering is disturbed. Such a disturbed nuclear architecture may then trigger the activation of a cell cycle checkpoint which has been previously suggested to be a major cause of hybrid lethality (Gerland, 2017).

    Altogether, these data provide a novel link between HMR and cis-regulatory elements bound by insulator proteins. It is speculated that divergent evolution of such genomic elements and their corresponding binding factors in sibling species is triggering hybrid incompatibilities (Gerland, 2017).

    Persistent postmating, prezygotic reproductive isolation between populations

    Studying reproductive barriers between populations of the same species is critical to understand how speciation may proceed. Growing evidence suggests postmating, prezygotic (PMPZ) reproductive barriers play an important role in the evolution of early taxonomic divergence. However, the contribution of PMPZ isolation to speciation is typically studied between species in which barriers that maintain isolation may not be those that contributed to reduced gene flow between populations. Moreover, in internally fertilizing animals, PMPZ isolation is related to male ejaculate-female reproductive tract incompatibilities but few studies have examined how mating history of the sexes can affect the strength of PMPZ isolation and the extent to which PMPZ isolation is repeatable or restricted to particular interacting genotypes. This study addressed these outstanding questions using multiple populations of Drosophila montana. A recurrent pattern of PMPZ isolation is shown, with flies from one population exhibiting reproductive incompatibility in crosses with all three other populations, while those three populations were fully fertile with each other. Reproductive incompatibility is due to lack of fertilization and is asymmetrical, affecting female fitness more than males. There was no effect of male or female mating history on reproductive incompatibility, indicating that PMPZ isolation persists between populations. No evidence was found of variability in fertilization outcomes attributable to different female x male genotype interactions, and in combination with other results, suggests that PMPZ isolation is not driven by idiosyncratic genotype x genotype interactions. These results show PMPZ isolation as a strong, consistent barrier to gene flow early during speciation and suggest several targets of selection known to affect ejaculate-female reproductive tract interactions within species that may cause this PMPZ isolation (Garlovsky, 2018).

    The hpRNA/RNAi pathway is essential to resolve intragenomic conflict in the Drosophila male germline

    Intragenomic conflicts are fueled by rapidly evolving selfish genetic elements, which induce selective pressures to innovate opposing repressive mechanisms. This is patently manifest in sex-ratio (SR) meiotic drive systems, in which distorter and suppressor factors bias and restore equal transmission of X and Y sperm. This study reveals that multiple SR suppressors in Drosophila simulans (Nmy and Tmy) encode related hairpin RNAs (hpRNAs), which generate endo-siRNAs that repress the paralogous distorters Dox and MDox. All components in this drive network are recently evolved and largely testis restricted. To connect SR hpRNA function to the RNAi pathway, D. simulans null mutants of Dcr-2 and AGO2 were generated. Strikingly, these core RNAi knockouts massively derepress Dox and MDox and are in fact completely male sterile and exhibit highly defective spermatogenesis. Altogether, these data reveal how the adaptive capacity of hpRNAs is critically deployed to restrict selfish gonadal genetic systems that can exterminate a species (Lin, 2018).

    RNA interference (RNAi) has long been recognized as a versatile experimental technique, but its endogenous biological utilities have been less tangible. This topic is in principle more accessible in invertebrates, several of which express diverse endogenous siRNAs (endo-siRNAs) via dedicated RNAi machinery that is distinct from the related miRNA pathway. However, while RNAi mutants in nematodes and flies are compromised at defending viruses and affected by certain extreme environmental perturbations, RNAi mutants generally exhibit few overt phenotypes under non-sensitized conditions (Lin, 2018).

    The biological logic of the Drosophila hairpin RNA (hpRNA) pathway has been described, in which inverted repeat transcripts preferentially generate endo-siRNAs in the testis and repress specific highly complementary mRNAs. Although all known hpRNAs are recently evolved, clear evidence is observed for siRNA:target co-evolution, indicating adaptive properties of this regulatory network. While ovaries detectably express hpRNAs and endo-siRNAs, RNAi mutants have relatively little consequence in females. Instead, genetic ablation of RNAi causes spermatogenesis defects and male subfertility. Nevertheless, Drosophila melanogaster RNAi mutant males are fertile, suggesting this species can formally cope without siRNAs, at least within the laboratory setting (Lin, 2018).

    In searching for other manifestations of the hpRNA pathway, the Winters sex-ratio (SR) system of Drosophila simulans was investigated. This meiotic drive system is absent from D. melanogaster and was born within D. simulans subclade species that diverged ~240,000 years ago. Despite its recent de novo appearance, Winters SR factors have profound activities. The Distorter on X (Dox) promotes X chromosome transmission by suppressing Y-bearing sperm, a patently undesirable 'wild-type' gene activity that must be silenced in order to maintain the D. simulans species. An antidote is encoded by autosomal Not much yang (Nmy), to which an inverted repeat with a sequence similarity to Dox was mapped. Signatures consistent with positive selection on Winters factors have been detected within D. simulans populations, indicating the system is actively evolving under an 'arms-race' scenario. While the relationship of Dox and Nmy was evocative of homology-dependent silencing, there is currently no evidence (1) for molecular species constituting the active output of Nmy, (2) that Nmy directly or indirectly regulates the expression of Dox, (3) whether Winters factors are truly distinct from other SR systems, or (4) that the RNAi pathway participates in SR control (Lin, 2018).

    This study provides first molecular evidence that hpRNA-siRNAs are functional mediators of son protection in the Winters SR system. Moreover, this study reveals that a second, previously uncloned SR suppressor in this species, known as the Durham SR system, involves a previously unknown hpRNA-siRNA locus termed Tmy. Although defined as genetically separable SR systems, this study also shows that Nmy and Tmy are paralogous and have partially overlapping capacity to suppress both Dox as well as its progenitor locus MDox. To demonstrate a connection to the RNAi pathway, CRISPR/Cas9 was used to engineer dcr-2 and ago2 null mutants in this non-model fruit fly species. Remarkably, these exhibit profound, testis-specific phenotypes that are much more severe than their well-studied D. melanogaster counterparts, in that they are completely male sterile due to profound defects in spermatogenesis progression and harbor massive synergistic derepression of Dox and MDox transcripts, consistent with loss of collaborative suppression by Nmy and Tmy hpRNAs (Lin, 2018).

    Altogether, these data demonstrate unanticipated complexity of sex-distorting factors and hpRNA-suppressing loci in D. simulans, all of which are rapidly evolving and none of which exist in D. melanogaster. Thus, RNAi is a key pathway that resolves intragenomic conflict that ensures species survival and fulfills roles in adaptive gonadal gene regulation that are more commonly attributed to the piRNA pathway. This highlights the need to explore a wider range of species to more fully appreciate the evolving functions of germline small RNA pathways (Lin, 2018).

    This study provides critical linkages among the RNAi pathway, hpRNA biogenesis and function, and suppression of SR bias. The evolutionary behavior of SR systems conforms to a 'Red Queen' effect, in which a seemingly static outcome (equal transmission of X and Y sperm) actually involves intense, opposing and rapidly evolving genetic programs. These studies provide striking evidence that endogenous RNAi is a central molecular pathway that resolves SR distortion and may potentially have an impact on hybrid sterility. Molecular and genetic evidence are provided of a potential hierarchy, in that Dox is a prime direct target of Nmy based on the observation that it supplies the majority of targeting siRNAs. Nevertheless, Tmy provides a secondary defense: since Tmy exhibits extensive complementarity to Dox that is non-overlapping with Nmy, Tmy siRNAs maintain targeting to Dox even in nmy mutants. Tmy can directly repress Dox in sensor assays, and most importantly, RNAi mutants exhibit strongly elevated Dox transcripts in testis, consistent with co-targeting endogenous action of both hpRNAs on Dox. Moreover, these principles are shown to be true for MDox, strongly implying this locus as a functional distorter. Overall, this study reveals that multiple evolutionary nascent hpRNAs (Nmy/Tmy) are individually required for species preservation via suppression of Winters and Durham SR (Dox/MDox) distorters in D. simulans (Lin, 2018).

    In the future, further dissection of the genetic contributions of the individual hpRNAs and distorters will shed light on their relative contributions to Winters and Durham SR systems and the extent to which they are distinct systems or partially overlapping as indicated by our studies. This will be a challenge in a non-model fly that lacks the genetic tools available in D. melanogaster but will be important to understand how these newly emerging factors are endowed with such powerful activities. For example, compelling hypotheses to test include whether specific deletions of the Tmy hairpin alone can recapitulate SR bias, whether Tmy exhibits derepression of other distorter factors, and whether nmy/tmy double mutant might exhibit only SR or may prove to recapitulate sterility found in RNAi mutants. Thus far, Nmy and Tmy loci have proven recalcitrant to repeated attempts for CRISPR/Cas9 targeting, and it is not clear whether something about their repeat structure affects this endeavor. Moreover, the close linkage of these loci will be a challenge for any efforts to generate recombinants. Still, it will be worthwhile to pursue the generation of new genetic tools (Lin, 2018).

    Remarkably, there is a third SR distortion system in D. simulans ('Paris'). While it is genetically complex, it was recently shown to depend on HP1D2, a recently evolved paralog of the piRNA factor Rhino. Thus, there are apparently molecular linkages of SR systems with small RNA systems, on both driving and suppressing sides. Although the mechanism of Paris SR remains to be determined, HP1D2 protein localizes to the heterochromatic Y chromosome, which provides a connection to the observation that driving Paris alleles prevent segregation of Y chromatids during meiosis II. On the other hand, the defect in Winters SR appears to be post-meiotic, indicating mechanistic diversity in how depletion of male sperm might be achieved by de novo genes (Lin, 2018).

    On the other hand, the sister species D. melanogaster appears to lack SR systems, testament to the extremely rapid rise and fall of SR systems during evolution. The adaptive properties of hpRNAs make them ideal genetic elements to tame such selfish meiotic drive elements, which are theorized to be under constant cycles of emergence, suppression, and disappearance. There is mounting evidence that genetic systems that manifest in SR defects are often associated with sterility. The findings of this study support the notion that the success or failure to resolve intragenomic conflicts using RNAi would be intimately connected to speciation (Lin, 2018).

    While these roles were unexpected in light of the fact that metazoan RNAi biology has been so challenging to appreciate, the situation would have been different had a species only slightly diverged from D. melanogaster initially been selected as a genetic model. This parallels the inference that RNAi might have been recognized earlier had certain budding yeasts other than Saccharomyces cerevisiae been studied earlier. Indeed, functional studies across a broader phylogeny will be necessary to appreciate the evolving requirements of small RNA regulation, beyond standard model organisms. The availability of the D. simulans RNAi mutants of this study opens the door to molecular identification of novel selfish genetic elements that induce SR bias and/or hybrid sterility, in both the Winters and Durham systems (Lin, 2018).

    Strength of sexual and postmating prezygotic barriers varies between sympatric populations with different histories and species abundances

    The impact of different reproductive barriers on species or population isolation may vary in different stages of speciation depending on evolutionary forces acting within species and through species' interactions. Genetic incompatibilities between interacting species are expected to reinforce prezygotic barriers in sympatric populations and lead to cascade reinforcement between conspecific populations living within and outside the areas of sympatry. These predictions were tested and this work studied whether and how the strength and target of reinforcement between Drosophila montana and Drosophila flavomontana vary between sympatric populations with different histories and species abundances. All barriers between D. montana females and D. flavomontana males were nearly complete, while in the reciprocal cross strong postzygotic isolation was accompanied by prezygotic barriers whose strength varied according to population composition. Sexual isolation between D. flavomontana females and D. montana males was increased in long-established sympatric populations, where D. flavomontana is abundant, while postmating prezygotic (PMPZ) barriers were stronger in populations where this species is a new invader and still rare and where female discrimination against heterospecific males was lower. Strengthening of sexual and PMPZ barriers in this cross also induced cascade reinforcement of respective barriers between D. flavomontana populations, which is a classic signature of reinforcement process (Poikela, 2019).

    Reproductive capacity evolves in response to ecology through common changes in cell number in Hawaiian Drosophila

    Lifetime reproductive capacity is a critical fitness component. In insects, female reproductive capacity is largely determined by the number of ovarioles, the egg-producing subunits of the ovary. Recent work has provided insights into ovariole number regulation in Drosophila melanogaster. However, whether mechanisms discovered under laboratory conditions explain evolutionary variation in natural populations is an outstanding question. This study investigated potential effects of ecology on the developmental processes underlying ovariole number evolution among Hawaiian Drosophila, a large adaptive radiation wherein the highest and lowest ovariole numbers of the family have evolved within 25 million years. Previous studies proposed that ovariole number correlated with oviposition substrate but sampled largely one clade of these flies and were limited by a provisional phylogeny and the available comparative methods. This hypothesis was tested by applying phylogenetic modeling to an expanded sampling of ovariole numbers and substrate types and shows support for these predictions across all major groups of Hawaiian Drosophila, wherein ovariole number variation is best explained by adaptation to specific substrates. Furthermore, oviposition substrate evolution is linked to changes in the allometric relationship between body size and ovariole number. Finally, evidence is provided that the major changes in ovarian cell number that regulate D. melanogaster ovariole number also regulate ovariole number in Hawaiian drosophilids. Thus, evidence is provided that this remarkable adaptive radiation is linked to evolutionary changes in a key reproductive trait regulated at least partly by variation in the same developmental parameters that operate in the model species D. melanogaster (Sarikaya, 2019).

    A common suite of cellular abnormalities and spermatogenetic errors in sterile hybrid males in Drosophila

    When two species interbreed, the resulting hybrid offspring are often sterile, with the heterogametic (e.g. XY) hybrid usually being more severely affected. The prevailing theory for this pattern of sterility evokes divergent changes in separate lineages having maladaptive interactions when placed together in a hybrid individual, with recessive factors on the sex chromosome interacting with dominant factors on the autosomes. The effect of these interactions on gametogenesis should not be uniform across species pairs unless genetic divergence follows the same paths in different lineages or if a specific stage of gametogenesis is more susceptible to detrimental genetic interactions. A detailed cellular characterization of hybrid male sterility was performed across three recently diverged species pairs of Drosophila. Across all three pairs, sterile hybrid sperm are alive but exhibit rapid nuclear de-condensation with age, with active, but non-differentiated, mitochondria. Surprisingly, all three sets of interspecies hybrids produce half of the number of sperm per round of spermatogenesis, with each sperm cell containing two tails. Non-disjunction failures during meiosis I were identified as the likely cause. Thus, errors during meiosis I may be a general phenomenon underlying Drosophila male sterility, indicating either a heightened sensitivity of this spermatogenic stage to failure, or a basis to sterility other than the prevailing model (Kanippayoor, 2020).

    Parallel sequencing of Wolbachia wCer2 from donor and novel hosts reveals multiple incompatibility factors and genome stability after host transfers

    The application of Wolbachia in insect pest and vector control requires the establishment of genotypically stable host associations. The cytoplasmic incompatibility (CI) inducing Wolbachia strain wCer2 naturally occurs in the cherry fruit fly Rhagoletis cerasi as co-infection with other strains and was transferred to other fruit flies by embryonic microinjections. wCer2 genome data was obtained from its native and three novel hosts, Drosophila simulans, Drosophila melanogaster and Ceratitis capitata and assessed its genome stability, characteristics, and CI factor (cif) genes. De novo assembly was successful from Wolbachia cell-enriched singly infected D. simulans embryos, with minimal host and other bacterial genome traces. The low yield of Wolbachia sequence reads from total genomic extracts of one multiply infected R. cerasi pupa and one singly infected C. capitata adult limited de novo assemblies but was sufficient for comparative analyses. Across hosts wCer2 was stable in genome synteny and content. Polymorphic nucleotide sites were found in wCer2 of each host, however only one nucleotide was different between R. cerasi and C. capitata, and none between replicated D. simulans lines. The wCer2 genome is highly similar to wAu (D. simulans), wMel (D. melanogaster) and wRec (Drosophila recens). In contrast to wMel and wRec (each with one cif gene pair) and wAu (without any cif genes), wCer2 has three pairs of Type I cif genes and one Type IV cifB gene without a cifA complement. This may explain previously reported CI patterns of wCer2, including incomplete rescue of its own CI modification in three novel host species (Morrow, 2020).

    Reproductive isolation caused by azoospermia in sterile male hybrids of Drosophila

    Recently diverged populations in the early stages of speciation offer an opportunity to understand mechanisms of isolation and their relative contributions. Drosophila willistoni is a tropical species with broad distribution from Argentina to the southern United States, including the Caribbean islands. A postzygotic barrier between northern populations (North America, Central America, and the northern Caribbean islands) and southern populations (South American and the southern Caribbean islands) has been recently documented and used to propose the existence of two different subspecies. This study has identified premating isolation between populations regardless of their subspecies status. No evidence of postmating prezygotic isolation was found, and this study proceeded to characterize hybrid male sterility between the subspecies. Sterile male hybrids transfer an ejaculate that is devoid of sperm but causes elongation and expansion of the female uterus. In sterile male hybrids, bulging of the seminal vesicle appears to impede the movement of the sperm toward the sperm pump, where sperm normally mixes with accessory gland products. The results highlight a unique form of hybrid male sterility in Drosophila that is driven by a mechanical impediment to transfer sperm rather than by an abnormality of the sperm itself. Interestingly, this form of sterility is reminiscent of a form of infertility (azoospermia) that is caused by lack of sperm in the semen due to blockages that impede the sperm from reaching the ejaculate (Davis, 2020).

    A morphological trait involved in reproductive isolation between Drosophila sister species is sensitive to temperature

    Male genitalia are usually extremely divergent between closely related species, but relatively constant within one species. This study examined the effect of temperature on the shape of the ventral branches, a male genital structure involved in reproductive isolation, in the sister species Drosophila santomea and Drosophila yakuba. A semi-automatic measurement machine learning pipeline was designed that can reliably identify curvatures and landmarks based on manually digitized contours of the ventral branches. With this method, it was observed that temperature does not affect ventral branches in D. yakuba but that in D. santomea ventral branches tend to morph into a D. yakuba-like shape at lower temperature. Male genitalia structures involved in reproductive isolation can be relatively variable within one species and can resemble the shape of closely related species' genitalia through plasticity to temperature. These results suggest that reproductive isolation mechanisms can be dependent on the environmental context (Peluffo, 2021).

    Defective satellite DNA clustering into chromocenters underlies hybrid incompatibility in Drosophila

    Although rapid evolution of pericentromeric satellite DNA repeats is theorized to promote hybrid incompatibility (HI), how divergent repeats affect hybrid cells remains poorly understood. Recently, it was demonstrated that sequence-specific DNA-binding proteins cluster satellite DNA from multiple chromosomes into 'chromocenters', thereby bundling chromosomes to maintain the entire genome in a single nucleus. This study shows that ineffective clustering of divergent satellite DNA in the cells of Drosophila hybrids results in chromocenter disruption, associated micronuclei formation and tissue atrophy. It was further demonstrated that previously identified HI factors trigger chromocenter disruption and micronuclei in hybrids, linking their function to a conserved cellular process. Together, a unifying framework is proposed that explains how the widely observed satellite DNA divergence between closely related species can cause reproductive isolation (Jagannathan, 2021).

    Complex basis of hybrid female sterility and Haldane's rule in Heliconius butterflies: Z-linkage and epistasis

    Hybrids between species are often sterile or inviable. Hybrid unfitness usually evolves first in the heterogametic sex - a pattern known as Haldane's rule. The genetics of Haldane's Rule have been extensively studied in species where the male is the heterogametic (XX/XY) sex, but its basis in taxa where the female is heterogametic (ZW/ZZ), such as Lepidoptera and birds, is largely unknown. This study analysed a new case of female hybrid sterility between geographic subspecies of Heliconius pardalinus. The two subspecies mate freely in captivity, but female F1 hybrids in both directions of cross are sterile. Sterility is due to arrested development of oocytes after they become differentiated from nurse cells, but before yolk deposition. Fertile male F1 hybrids were crossed to parental females, and quantitative trait loci (QTLs) were mapped for female sterility. Genes differentially expressed in the ovary and as a function of oocyte development were also identified. The Z chromosome has a major effect, similar to the "large X effect" in Drosophila, with strong epistatic interactions between loci at either end of the Z chromosome, and between the Z chromosome and autosomal loci on chromosomes 8 and 20. By intersecting the list of genes within these QTLs with those differentially expressed in sterile and fertile hybrids, three candidate genes were identified with relevant phenotypes. This study is the first to characterize hybrid sterility using genome mapping in the Lepidoptera, and shows that it is produced by multiple complex epistastic interactions often involving the sex chromosome, as predicted by the dominance theory of Haldane's Rule (Rosser, 2021).

    Evolution of reproductive isolation in a long-term evolution experiment with Drosophila melanogaster: 30 years of divergent life-history selection

    This study asked if three decades and over 1,500 generations of divergent life-history selection on age at reproduction has resulted in the evolution of reproductive isolation (RI) between laboratory populations of Drosophila melanogaster. Tests were performed for premating, postmating-prezygotic, and postzygotic reproductive isolation between three replicate population pairs. Large, evolved differences in body size between selection treatments suggested the potential for prezygotic barriers driven by sexual selection or physical incompatibilities between the sexes. Although a simple prediction would be preference for larger size, creating directional isolation, the results from individual mate choice trials indicate that populations from both selection treatments show a marked bias towards homotypic mate choice; indicative of prezygotic RI driven by sexual selection or sexual conflict. Hybridization between the focal populations resulted in the production of viable adult flies with intermediate size and developmental traits. A suggestive but statistically nonsignificant trend of fitness decline was observed in the F2 generation of hybrids, but no significant evidence suggesting the evolution of postmating-prezygotic or postzygotic RI. These findings are in accord with extant literature that posits that premating RI evolves before postmating forms of RI (Robinson, 2023).

    Identification of misexpressed genetic elements in hybrids between Drosophila-related species

    Crosses between close species can lead to genomic disorders, often considered to be the cause of hybrid incompatibility, one of the initial steps in the speciation process. How these incompatibilities are established and what are their causes remain unclear. To understand the initiation of hybrid incompatibility, reciprocal crosses were performed between two species of Drosophila (D. mojavensis and D. arizonae) that diverged less than 1 Mya. A genome-wide transcriptomic analysis was performed on ovaries from parental lines and on hybrids from reciprocal crosses. Using an innovative procedure of co-assembling transcriptomes, it was shown that parental lines differ in the expression of their genes and transposable elements. Reciprocal hybrids presented specific gene categories and few transposable element families misexpressed relative to the parental lines. Because TEs are mainly silenced by piwi-interacting RNAs (piRNAs), it was hypothesized that in hybrids the deregulation of specific TE families is due to the absence of such small RNAs. Small RNA sequencing confirmed the hypothesis, and it is therefore proposed that TEs can indeed be major players of genome differentiation and be implicated in the first steps of genomic incompatibilities through small RNA regulation (Lopez-Maestre, 2017).

    Introduction of a male-harming mitochondrial haplotype via 'Trojan Females' achieves population suppression in fruit flies

    Pests are a global threat to biodiversity, ecosystem function, and human health. Pest control approaches are thus numerous, but their implementation costly, damaging to non-target species, and ineffective at low population densities. The Trojan Female Technique (TFT) is a prospective self-perpetuating control technique that is species-specific and predicted to be effective at low densities. The goal of the TFT is to harness naturally-occurring mutations in the mitochondrial genome that impair male fertility while having no effect on females. This study provides proof-of-concept for the TFT, by showing that introduction of a male fertility-impairing mtDNA haplotype into replicated populations of Drosophila melanogaster causes numerical population suppression, with the magnitude of effect positively correlated with its frequency at trial inception. Further development of the TFT could lead to establishing a control strategy that overcomes limitations of conventional approaches, with broad applicability to invertebrate and vertebrate species, to control environmental and economic pests (Wolff, 2017).

    Male mate choice via cuticular hydrocarbon pheromones drives reproductive isolation between Drosophila species

    Mate discrimination is a key mechanism restricting gene flow between species. While studied extensively with respect to female mate choice, mechanisms of male mate choice between species are far less studied. Thus, there is little knowledge of the relative frequency, importance, or overall contribution of male mate discrimination to reproductive isolation. This study estimated the relative contributions of male and female choice to reproductive isolation between Drosophila simulans and D. sechellia, and showed that male mate discrimination accounts for the majority of the current isolation between these species. It was further demonstrate that males discriminate based on female cuticular hydrocarbon pheromones, and collect evidence supporting the hypothesis that male mate discrimination may alleviate the costs associated with heterospecific courtship and mating. These findings highlight the potentially significant contribution of male mate choice to the formation of reproductive isolating barriers, and thus the speciation process (Shahandeh, 2017).

    Genes underlying species differences in CHC production between Drosophila melanogaster and D. simulans

    Surface chemical compounds are key components of survival and reproduction in many species. Cuticular hydrocarbons (CHCs) are chemical compounds produced by all insects that are used for both desiccation resistance and chemical communication, including communication related to mating. In the species pair of Drosophila melanogaster and D. simulans, female CHCs stimulate conspecific males to mate and repel heterospecific males. While CHCs are a critical contributor to both reproductive success within a species and isolation between species, few genes underlying species variation in CHC profiles are known. This study used genetic mapping of the 3rd chromosome to test a suite of candidate genes for interspecies variation in CHCs. Candidate gene CG5946 was found to be involved in species differences in the production of 7,11-heptacosadiene and 7-tricosene between D. melanogaster and D. simulans. This is therefore a new candidate locus contributing to species-specific variation in the CHC profile. In the process of mapping genes for CHCs, 29 candidate genes for the reduced survival or inviability of interspecies hybrids were identified (Ward, 2020).

    The rate of evolution of postmating-prezygotic reproductive isolation in Drosophila

    Reproductive isolation is an intrinsic aspect of species formation. For that reason, the identification of the precise isolating traits, and the rates at which they evolve, is crucial to understanding how species originate and persist. Previous work has measured the rates of evolution of prezygotic and postzygotic barriers to gene flow, yet no systematic analysis has studied the rates of evolution of postmating-prezygotic (PMPZ) barriers. This study measured the magnitude of two barriers to gene flow that act after mating occurs but before fertilization. The magnitude of a premating barrier (female mating rate in nonchoice experiments) and two postzygotic barriers (hybrid inviability and hybrid sterility) was also measured for all pairwise crosses of all nine known extant species within the melanogaster subgroup. The results indicate that PMPZ isolation evolves faster than hybrid inviability but slower than premating isolation. Next, postzygotic isolation was partitioned into different components; as expected, hybrid sterility evolves faster than hybrid inviability. These results lend support for the hypothesis that, in Drosophila, reproductive isolation mechanisms (RIMs) that act early in reproduction (or in development) tend to evolve faster than those that act later in the reproductive cycle. Finally, whether there was evidence for reinforcing selection at any RIM was tested. No evidence was found for generalized evolution of reproductive isolation via reinforcement which indicates that there is no pervasive evidence of this evolutionary process. These results indicate that PMPZ RIMs might have important evolutionary consequences in initiating speciation and in the persistence of new species (Turissini, 2017).

    Genomic changes following the reversal of a Y chromosome to an autosome in Drosophila pseudoobscura

    Robertsonian translocations resulting in fusions between sex chromosomes and autosomes shape Karyotype evolution by creating new sex chromosomes from autosomes. These translocations can also reverse sex chromosomes back into autosomes, which is especially intriguing given the dramatic differences between autosomes and sex chromosomes. To study the genomic events following a Y chromosome reversal, this study investigated an autosome-Y translocation in Drosophila pseudoobscura. The ancestral Y chromosome fused to a small autosome (the dot chromosome) approximately 10-15 Mya. Single molecule real-time sequencing reads were used to assemble the D. pseudoobscura dot chromosome, including the Y-to-dot translocation. It was found that the intervening sequence between the ancestral Y and the rest of the dot chromosome is only ∼78 Kb and is not repeat-dense, suggesting that the centromere now falls outside, rather than between, the fused chromosomes. The Y-to-dot region is 100 times smaller than the D. melanogaster Y chromosome, owing to changes in repeat landscape. However, a consistent reduction in intron sizes across the Y-to-dot region was not found. Instead, deletions in intergenic regions and possibly a small ancestral Y chromosome size may explain the compact size of the Y-to-dot translocation (Chang, 2017).

    Linked genetic variation and not genome structure causes widespread differential expression associated with chromosomal inversions

    Chromosomal inversions are widely thought to be favored by natural selection because they suppress recombination between alleles that have higher fitness on the same genetic background or in similar environments. Nonetheless, few selected alleles have been characterized at the molecular level. Gene expression profiling provides a powerful way to identify functionally important variation associated with inversions and suggests candidate phenotypes. This study characterized differential expression patterns associated with two chromosomal inversions found in natural Drosophila melanogaster populations. To isolate the impacts of genome structure, synthetic chromosomal inversions were engineered on controlled genetic backgrounds with breakpoints that closely match each natural inversion. Synthetic inversions have negligible effects on gene expression. Nonetheless, natural inversions have broad-reaching regulatory impacts in cis and trans Furthermore, differentially expressed genes associated with both natural inversions are enriched for loci associated with immune response to bacterial pathogens. The results support the idea that inversions in D. melanogaster experience natural selection to maintain associations between functionally related alleles to produce complex phenotypic outcomes (Said, 2018).

    An investigation of Y chromosome incorporations in 400 species of Drosophila and related genera

    Y chromosomes are widely believed to evolve from a normal autosome through a process of massive gene loss (with preservation of some male genes), shaped by sex-antagonistic selection and complemented by occasional gains of male-related genes. The net result of these processes is a male-specialized chromosome. This might be expected to be an irreversible process, but it was found in 2005 that the Drosophila pseudoobscura Y chromosome was incorporated into an autosome. Y chromosome incorporations have important consequences: a formerly male-restricted chromosome reverts to autosomal inheritance, and the species may shift from an XY/XX to X0/XX sex-chromosome system. In order to assess the frequency and causes of this phenomenon Y chromosome incorporations was sought in 400 species from Drosophila and related genera. One additional large scale event of Y chromosome incorporation was found, affecting the whole montium subgroup (40 species in our sample); overall 13% of the sampled species (52/400) have Y incorporations. While previous data indicated that after the Y incorporation the ancestral Y disappeared as a free chromosome, the much larger data set analyzed here indicates that a copy of the Y survived as a free chromosome both in montium and pseudoobscura species, and that the current Y of the pseudoobscura lineage results from a fusion between this free Y and the neoY. The 400 species sample also showed that the previously suggested causal connection between X-autosome fusions and Y incorporations is, at best, weak: the new case of Y incorporation (montium) does not have X-autosome fusion, whereas nine independent cases of X-autosome fusions were not followed by Y incorporations. Y incorporation is an underappreciated mechanism affecting Y chromosome evolution; these results show that at least in Drosophila it plays a relevant role and highlight the need of similar studies in other groups (Dupim, 2018).

    The molecular characterization of fixed inversions breakpoints unveils the ancestral character of the Drosophila guanche chromosomal arrangements

    Cytological studies revealed that the number of chromosomes and their organization varies across species. The increasing availability of whole genome sequences of multiple species across specific phylogenies has confirmed and greatly extended these cytological observations. In the Drosophila genus, the ancestral karyotype consists of five rod-like acrocentric chromosomes (Muller elements A to E) and one dot-like chromosome (element F), each exhibiting a generally conserved gene content. Chromosomal fusions and paracentric inversions are thus the major contributors, respectively, to chromosome number variation among species and to gene order variation within chromosomal element. The subobscura cluster of Drosophila consists in three species that retain the genus ancestral karyotype and differ by a reduced number of fixed inversions. This study used cytological information and the D. guanche genome sequence to identify and molecularly characterize the breakpoints of inversions that became fixed since the D. guanche-D. subobscura split. The results have led to a proposal of a modified version of the D. guanche cytological map of its X chromosome, and to establish that (i) most inversions became fixed in the D. subobscura lineage and (ii) the order in which the four X chromosome overlapping inversions occurred and became fixed (Orengo. 2019).

    Structural variants exhibit widespread allelic heterogeneity and shape variation in complex traits

    It has been hypothesized that individually-rare hidden structural variants (SVs) could account for a significant fraction of variation in complex traits. This study identified more than 20,000 euchromatic SVs from 14 Drosophila melanogaster genome assemblies, of which ~40% are invisible to high specificity short-read genotyping approaches. SVs are common, with 31.5% of diploid individuals harboring a SV in genes larger than 5kb, and 24% harboring multiple SVs in genes larger than 10kb. SV minor allele frequencies are rarer than amino acid polymorphisms, suggesting that SVs are more deleterious. A number of functionally important genes were shown to harbor previously hidden structural variants likely to affect complex phenotypes. Furthermore, SVs are overrepresented in candidate genes associated with quantitative trait loci mapped using the Drosophila Synthetic Population Resource. It is concluded that SVs are ubiquitous, frequently constitute a heterogeneous allelic series, and can act as rare alleles of large effect (Chakraborty, 2019).

    Complex evolutionary history of the Y chromosome in flies of the Drosophila obscura species group

    The Drosophila obscura species group shows dramatic variation in karyotype, including transitions among sex chromosomes. Members of the affinis and pseudoobscura subgroups contain a neo-X chromosome (a fusion of the X with an autosome), and it was shown that ancestral Y genes have become autosomal in species harboring the neo-X. Detailed analysis of species in the pseudoobscura subgroup revealed that ancestral Y genes became autosomal through a translocation to the small dot chromosome. This study shows that the Y-dot translocation is restricted to the pseudoobscura subgroup, and translocation of ancestral Y genes in the affinis subgroup likely followed a different route. Most ancestral Y genes appear to have translocated to unique autosomal or X-linked locations in different taxa of the affinis subgroup, and a dynamic model of sex chromosome formation and turnover in the obscura species group is proposed. The results suggest that Y genes can find unique paths to escape unfavorable genomic environments that form after sex chromosome-autosome fusions (Bracewell, 2020).

    Fine-scale position effects shape the distribution of inversion breakpoints in Drosophila melanogaster

    Chromosomal inversions are among the primary drivers of genome structure evolution in a wide range of natural populations. While there is an impressive array of theory and empirical analyses that have identified conditions under which inversions can be positively selected, comparatively little data is available on the fitness impacts of these genome structural rearrangements themselves. Because inversion breakpoints can disrupt functional elements and alter chromatin domains, the precise positioning of an inversion's breakpoints can strongly affect its fitness. This study compared the fine-scale distribution of low frequency inversion breakpoints with those of high frequency inversions and inversions that have gone to fixation between Drosophila species. A number of differences were identified among frequency classes that may influence inversion fitness. In particular, breakpoints that are proximal to insulator elements, generate large tandem duplications, and minimize impacts on gene coding spans are more prevalent in high frequency and fixed inversions than in rare inversions. The data suggest that natural selection acts to preserve both genes and larger cis-regulatory networks in the occurrence and spread of rearrangements. These factors may act to limit the availability of high fitness arrangements when suppressed recombination is favorable (McBroome, 2020).

    Shared evolutionary trajectories of three independent neo-sex chromosomes in Drosophila

    Dosage compensation (DC) on the X Chromosome counteracts the deleterious effects of gene loss on the Y Chromosome. However, DC is not efficient if the X Chromosome also degenerates. This indeed occurs in Drosophila miranda, in which both the neo-Y and the neo-X are under accelerated pseudogenization. To examine the generality of this pattern, this study investigated the evolution of two additional neo-sex chromosomes that emerged independently in D. albomicans and D. americana, and neo-sex chromosome evolution in D. miranda Comparative genomic and transcriptomic analyses revealed that the pseudogenization rate on the neo-X is also accelerated in D. albomicans and D. americana although to a lesser extent than in D. miranda. In males, neo-X-linked genes whose neo-Y-linked homologs are pseudogenized tended to be up-regulated more than those whose neo-Y-linked homologs remain functional. Moreover, genes under strong functional constraint and genes highly expressed in the testis tended to remain functional on the neo-X and neo-Y, respectively. Focusing on the D. miranda and D. albomicans neo-sex chromosomes that emerged independently from the same autosome, it was further found that the same genes tend to become pseudogenized in parallel on the neo-Y. These genes include Idgf6 and JhI-26, which may be unnecessary or even harmful in males. These results indicate that neo-sex chromosomes in Drosophila share a common evolutionary trajectory after their emergence, which may prevent sex chromosomes from being an evolutionary dead end (Nozawa, 2021).

    New Genes in the Drosophila Y Chromosome: Lessons from D. willistoni

    Y chromosomes play important roles in sex determination and male fertility. In several groups (e.g., mammals) there is strong evidence that they evolved through gene loss from a common X-Y ancestor, but in Drosophila the acquisition of new genes plays a major role. This conclusion came mostly from studies in two species. This study report the identification of the 22 Y-linked genes in D. willistoni. They all fit the previously observed pattern of autosomal or X-linked testis-specific genes that duplicated to the Y. The ratio of gene gains to gene losses is ~25 in D. willistoni, confirming the prominent role of gene gains in the evolution of Drosophila Y chromosomes. Four large segmental duplications (ranging from 62 kb to 303 kb) from autosomal regions to the Y, containing ~58 genes, were found. All but four of these duplicated genes became pseudogenes in the Y or disappeared. In the GK20609 gene the Y-linked copy remained functional, whereas its original autosomal copy degenerated, demonstrating how autosomal genes are transferred to the Y chromosome. Since the segmental duplication that carried GK20609 contained six other testis-specific genes, it seems that chance plays a significant role in the acquisition of new genes by the Drosophila Y chromosome (Ricchio, 2021).

    Cytological heterogeneity of heterochromatin among 10 sequenced Drosophila species

    In Drosophila chromosomal rearrangements can be maintained and are associated with karyotypic variability among populations from different geographic localities. The abundance of variability in gene arrangements among chromosomal arms is even greater when comparing more distantly related species and the study of these chromosomal changes has provided insights into the evolutionary history of species in the genus. Additionally, the sequencing of genomes of several Drosophila species has offered the opportunity to establish the global pattern of genomic evolution, at both genetic and chromosomal level. The combined approaches of comparative analysis of syntenic blocks and direct physical maps on polytene chromosomes have elucidated changes in the orientation of genomic sequences and the difference between heterochromatic and euchromatic regions. Unfortunately, the centromeric heterochromatic regions cannot be studied using the cytological maps of polytene chromosomes because they are underreplicated and therefore reside in the chromocenter. In D. melanogaster, a cytological map of the heterochromatin has been elaborated using mitotic chromosomes from larval neuroblasts. The current work has expanded on that mapping by producing cytological maps of the mitotic heterochromatin in an additional 10 sequenced Drosophila species. These maps highlight two apparently different paths, for the evolution of the pericentric heterochromatin between the subgenera Sophophora and Drosophila. One path leads towards a progressive complexity of the pericentric heterochromatin (Sophofora) and the other towards a progressive simplification (Drosophila). These maps are also useful for a better understanding how karyotypes have been altered by chromosome arm reshuffling during evolution (Marcella, 2022).

    Neo-sex chromosome evolution shapes sex-dependent asymmetrical introgression barrier

    Sex chromosomes play a special role in the evolution of reproductive barriers between species. This study describes conflicting roles of nascent sex chromosomes on patterns of introgression in an experimental hybrid swarm. Drosophila nasuta and Drosophila albomicans are recently diverged, fully fertile sister species that have different sex chromosome systems. The fusion between an autosome (Muller CD) with the ancestral X and Y gave rise to neo-sex chromosomes in D. albomicans, while Muller CD remains unfused in D. nasuta. This study found that a large block containing overlapping inversions on the neo-sex chromosome stood out as the strongest barrier to introgression. Intriguingly, the neo-sex chromosome introgression barrier is asymmetrical and sex-dependent. Female hybrids showed significant D. albomicans–biased introgression on Muller CD (neo-X excess), while males showed heterosis with excessive (neo-X, D. nasuta Muller CD) genotypes. A population genetic model was used to dissect the interplay of sex chromosome drive, heterospecific pairing incompatibility between the neo-sex chromosomes and unfused Muller CD, neo-Y disadvantage, and neo-X advantage in generating the observed sex chromosome genotypes in females and males. Moderate neo-Y disadvantage and D. albomicans specific meiotic drive were shown to be required to observe female-specific D. albomicans–biased introgression in this system, together with pairing incompatibility and neo-X advantage. In conclusion, this hybrid swarm between a young species pair sheds light onto the multifaceted roles of neo-sex chromosomes in a sex-dependent asymmetrical introgression barrier at a species boundary (Wang, 2022).

    Phylogenetic analysis of forkhead transcription factors in the Panarthropoda

    Fox genes encode transcription factors that contain a DNA binding domain, the forkhead domain, and are known from diverse animal species. The exact homology of the Fox genes of different species is debated and this makes inferences about the evolution of the Fox genes, and their duplications and losses difficult. We have performed phylogenetic analyses of the Fox gene complements of 32 panarthropod species. Our results confirm an ancestral complement of FoxA, FoxB, FoxC, FoxD, FoxF, FoxG, FoxJ1, FoxJ2/3, FoxK, FoxL1, FoxL2, FoxN1/4, FoxN2/3, FoxO, FoxP, and FoxQ2 in the Arthropoda, and additionally FoxH and FoxQ1 in the Panarthropoda (including tardigrades and onychophorans). We identify a novel Fox gene sub-family, that we designate as FoxT that includes two genes in Drosophila melanogaster, Circadianly Regulated Gene (Crg-1) and forkhead domain 3F (fd3F). In a very recent paper, the same new Fox gene sub-family was identified in insects. The current analysis confirms the presence of FoxT and shows that its members are present throughout Panarthropoda. The hitherto unclassified gene CG32006 from the fly Drosophila melanogaster belongs to FoxJ1. Gene losses were also detected: FoxE and FoxM were lost already in the panarthropod ancestor, whereas the loss of FoxH occurred in the arthropod ancestor. Finally, an ortholog of FoxQ1 was detected in the bark scorpion Centruroides sculpturatus, confirmed not only by phylogenetic analysis, but also by forming an evolutionarily conserved gene cluster with FoxF, FoxC, and FoxL1. This suggests that FoxQ1 belongs to the ancestral Fox gene complement in panarthropods and also in chelicerates, but has been lost at the base of the mandibulate arthropods (Schomburg, 2022).

    Phylogenetic annotation of Drosophila melanogaster heat shock protein 70 genes

    The traditional classification of stress-inducible 70 kDa heat shock protein (Hsp70) and heat shock cognate (Hsc70) requires a revision because of a recent finding that neither of them constitutes a monophyletic gene family. This study inferred a phylogenetic relationship among Drosophila melanogaster Hsp70 family members. D. melanogaster Hsp70 family members were separated into four known metazoan Hsp70 lineages: cytosolic A, cytosolic B, endoplasmic reticulum, and mitochondria. Hsc70s sporadically distributed in the phylogenetic tree, indicating their paraphyletic origin. Detailed sequence inspection found several motifs that support the phylogenetic analysis. Taken together, this study proposes new aliases of D. melanogaster Hsp70 family members based on their evolutionary history (Kaneko, 2022).

    Structural screens identify candidate human homologs of insect chemoreceptors and cryptic Drosophila gustatory receptor-like proteins

    Insect odorant receptors and gustatory receptors define a superfamily of seven transmembrane domain ion channels (referred to here as 7TMICs), with homologs identified across Animalia except Chordata. Previously, sequence-based screening methods were used to reveal conservation of this family in unicellular eukaryotes and plants (DUF3537 proteins). This study combined three-dimensional structure-based screening, ab initio protein folding predictions, phylogenetics, and expression analyses to characterize additional candidate homologs with tertiary but little or no primary structural similarity to known 7TMICs, including proteins in disease-causing Trypanosoma. Unexpectedly, structural similarity was identified between 7TMICs and PHTF proteins, a deeply conserved family of unknown function, whose human orthologs display enriched expression in testis, cerebellum, and muscle. Divergent groups of 7TMICs were found in insects, which was termed the gustatory receptor-like (Grl) proteins. Several Drosophila melanogaster Grls display selective expression in subsets of taste neurons, suggesting that they are previously unrecognized insect chemoreceptors. Although the possibility of remarkable structural convergence cannot be excluded, these findings support the origin of 7TMICs in a eukaryotic common ancestor, counter previous assumptions of complete loss of 7TMICs in Chordata, and highlight the extreme evolvability of this protein fold, which likely underlies its functional diversification in different cellular contexts (Benton, 2023).

    A comparative study of natural variation in hemolymph glucose levels under different dietary sugar conditions in Drosophila melanogaster and D. simulans

    Physiological responses to environmental changes play important roles in adaptive evolution. In particular, homeostatic regulatory systems that maintain constant circulating glucose levels are crucial in animals. However, variation in circulating glucose levels and the genetic effects on phenotypic variation in natural populations remain to be clarified. This study investigated the hemolymph glucose levels in natural populations of Drosophila melanogaster and its sibling species, D. simulans, in Japan. Hemolymph glucose concentrations were quantified in third instar larvae of 27 lines for each species, which were reared on either glucose-free or glucose-rich food. In both species, genetic variation was not a major component of phenotypic variation on either glucose-free or glucose-rich food. The hemolymph glucose concentrations were much higher in D. simulans than in D. melanogaster. Genetic variance was larger in D. simulans than in D. melanogaster. The observed differences between the two species may be associated with the much more recent colonization history of D. simulans populations in Japan and/or the tolerance to environmental stresses. These findings suggest that natural selection acting on hemolymph glucose levels in D. melanogaster is different from that in D. simulans (Inomata, 2023).

    A hidden markov model approach for simultaneously estimating local ancestry and admixture time using next generation sequence data in samples of arbitrary ploidy

    Admixture-the mixing of genomes from divergent populations-is increasingly appreciated as a central process in evolution. This study introduced a novel hidden Markov model for estimating local ancestry that models the read pileup data, rather than genotypes, is generalized to arbitrary ploidy, and can estimate the time since admixture during local ancestry inference. This method can simultaneously estimate the time since admixture and local ancestry with good accuracy, and it performs well on samples of high ploidy-i.e. 100 or more chromosomes. As this method is very general, it will be useful for local ancestry inference in a wider variety of populations than what previously has been possible. The method was applied to pooled sequencing data derived from populations of Drosophila melanogaster on an ancestry cline on the east coast of North America. Regions of local recombination rates were found to be negatively correlated with the proportion of African ancestry, suggesting that selection against foreign ancestry is the least efficient in low recombination regions. Finally it was shown that clinal outlier loci are enriched for genes associated with gene regulatory functions, consistent with a role of regulatory evolution in ecological adaptation of admixed D. melanogaster populations. These results illustrate the potential of local ancestry inference for elucidating fundamental evolutionary processes (Corbett-Detig, 2017).

    Sex and tissue-specific evolution of developmental plasticity in Drosophila melanogaster

    Developmental plasticity influences the size of adult tissues in insects. Tissues can have unique responses to environmental perturbation during development; however, the prevalence of within species evolution of tissue-specific developmental plasticity remains unclear. To address this, the effects of temperature and nutrition were studied on wing and femur size in D. melanogaster populations from a temperate and tropical region. Wings were more sensitive to temperature, while wings and femurs were equally responsive to nutrition in both populations and sexes. The temperate population was larger under all conditions, except for femurs of starved females. In line with this, greater femur size plasticity was observed in response to starvation in temperate females, leading to differences in sexual dimorphism between populations such that the slope of the reaction norm of sexual dimorphism in the tropical population was double that of the temperate population. Lastly, a significant trend was observed for steeper slopes of reaction norms in temperate than in tropical females, but not in males. These findings highlight that plasticity divergence between populations can evolve heterogeneously across sexes and tissues and that nutritional plasticity can alter sexual dimorphism in D. melanogaster (Sarikaya, 2021).

    Symbiont strain is the main determinant of variation in Wolbachia-mediated protection against viruses across Drosophila species

    Wolbachia is a common heritable bacterial symbiont in insects. Its evolutionary success lies in the diverse phenotypic effects it has on its hosts coupled to its propensity to move between host species over evolutionary timescales. In a survey of natural host-symbiont associations in a range of Drosophila species, this study found that 10 of 16 Wolbachia strains protected their hosts against viral infection. By moving Wolbachia strains between host species, the symbiont genome was found to have a much greater influence on the level of antiviral protection than the host genome. The reason for this was that the level of protection depended on the density of the symbiont in host tissues, and Wolbachia rather than the host controlled density. The finding that virus resistance and symbiont density are largely under the control of symbiont genes in this system has important implications both for the evolution of these traits and for public health programs using Wolbachia to prevent mosquitoes from transmitting disease (Martinez, 2017).

    Inter- and intra-species variation in genome-wide gene expression of Drosophila in response to parasitoid wasp attack

    A study of inter- and intra-species variation in resistance to parasitoid attack used RNA-seq after parasitization in lines experimentally selected for increased resistance. A core set of genes was found that are consistently up-regulated after parasitoid attack. Another set showed no up-regulation or expression in D. sechellia, the species unable to raise an immune response against parasitoids. This set consists largely of genes that are lineage-restricted to the melanogaster subgroup. Artificially selected lines did not show significant differences in gene expression with respect to non-selected lines, but several genes showed differential exon usage. This study has shown substantial similarities, but also notable differences, in the transcriptional responses to parasitoid attack among four closely related Drosophila species. In contrast, within D. melanogaster, the responses were remarkably similar. It was confirmed that in the short-term, selection does not act on a pre-activation of the immune response. Instead it may target alternative mechanisms such as differential exon usage. In the long-term, support was found for the hypothesis that the ability to immunologically resist parasitoid attack is contingent on new genes that are restricted to the melanogaster subgroup (Salazar-Jaramillo, 2017).

    Host-pathogen coevolution increases genetic variation in susceptibility to infection

    It is common to find considerable genetic variation in susceptibility to infection in natural populations. This study has investigated whether natural selection increases this variation by testing whether host populations show more genetic variation in susceptibility to pathogens that they naturally encounter than novel pathogens. In a large cross-infection experiment involving four species of Drosophila and four host-specific viruses, greater genetic variation was always found in susceptibility to viruses that had coevolved with their host. The genetic architecture of resistance was examined in one host species, finding that there are more major-effect genetic variants in coevolved host-pathogen interactions. It is concluded that selection by pathogens has increased genetic variation in host susceptibility, and much of this effect is caused by the occurrence of major-effect resistance polymorphisms within populations (Duxbury, 2019).

    Heritability and pre-adult survivorship costs of ectoparasite resistance in the naturally occurring Drosophila-Gamasodes mite system

    Our understanding of the evolutionary significance of ectoparasites in natural communities is limited by a paucity of information concerning the mechanisms and heritability of resistance to this ubiquitous group of organisms. This study reports the results of artificial selection for increasing ectoparasite resistance in replicate lines of Drosophila melanogaster derived from a field-fresh population. Resistance, as ability to avoid infestation by naturally co-occurring Gamasodes queenslandicus mites, increased significantly in response to selection, and realized heritability (s.e.) was estimated to be 0.11 (0.0090). Deployment of energetically expensive bursts of flight from the substrate was a main mechanism of host resistance that responded to selection, aligning with previously documented metabolic costs of fly behavioral defenses. Host body size, which affects parasitism rate in some fly-mite systems, was not shifted by selection. In contrast, resistant lines expressed significant reductions in larva-to-adult survivorship with increasing toxic (ammonia) stress, identifying an environmentally modulated pre-adult cost of resistance. Flies selected for resistance to G. queenslandicus were also more resistant to a different mite, Macrocheles subbadius, suggesting that we documented genetic variation and a pleiotropic cost of broad-spectrum behavioral immunity against ectoparasites. The results demonstrate significant evolutionary potential of resistance to an ecologically important class of parasites (Polak, 2023).

    A male-killing gene encoded by a symbiotic virus of Drosophila

    In most eukaryotes, biparentally inherited nuclear genomes and maternally inherited cytoplasmic genomes have different evolutionary interests. Strongly female-biased sex ratios that are repeatedly observed in various arthropods often result from the male-specific lethality (male-killing) induced by maternally inherited symbiotic bacteria such as Spiroplasma and Wolbachia. However, despite some plausible case reports wherein viruses are raised as male-killers, it is not well understood how viruses, having much smaller genomes than bacteria, are capable of inducing male-killing. This study showed that a maternally inherited double-stranded RNA (dsRNA) virus belonging to the family Partitiviridae (designated DbMKPV1) induces male-killing in Drosophila. DbMKPV1 localizes in the cytoplasm and possesses only four genes, i.e., one gene in each of the four genomic segments (dsRNA1-dsRNA4), in contrast to ca. 1000 or more genes possessed by Spiroplasma or Wolbachia. A protein (designated PVMKp1; 330 amino acids in size), encoded by a gene on the dsRNA4 segment, was shown to be necessary and sufficient for inducing male-killing. These results imply that male-killing genes can be easily acquired by symbiotic viruses through reassortment and that symbiotic viruses are hidden players in arthropod evolution. It is anticipated that host-manipulating genes possessed by symbiotic viruses can be utilized for controlling arthropods (Kageyama, 2023).

    Geographic variation in the spotted-wing drosophila, Drosophila suzukii (Diptera: Drosophilidae), based on mitochondrial DNA sequences

    The spotted-wing drosophila (SWD), Drosophila suzukii, is an economically damaging pest that was originally native to a few Asian countries, including Korea, but is now found in North America and Europe. Portions of the mitochondrial (mt) COI and ND4 genes were sequenced from a total of 195 individuals collected mainly from Korea. GenBank-registered COI sequences were combined with the COI data to assess the worldwide diversity, divergence, and relatedness of SWD haplotypes. A total of 139 haplotypes were obtained from the concatenated COI and ND4 sequences. Most haplotypes were confined to single localities, but 12 of them were found in more than two localities, and one haplotype (SWDCN61) was found from Korea to Canada. A dataset combining GenBank sequences with the current data identified a total of 94 worldwide COI haplotypes with a maximum sequence divergence (MSD) of 5.433% (32 bp). Although most haplotypes were found in only a single country, a few haplotypes were found commonly in China, Korea, and Japan; these occurred at a higher frequency and were often involved in introductions. A rough estimate of genetic diversity in each country showed higher diversity in ancestral distributional ranges, but the invasion over Asian countries seems to have been substantial because haplotype diversity was only 2.35 to 3.97-fold lower in the U.S.A, Canada, and Italy than that in the populations' ancestral ranges (Choi, 2017).

    Rapidly evolving Toll-3/4 genes encode male-specific Toll-like receptors in Drosophila

    Animal Toll-like receptors (TLRs) have evolved through a pattern of duplication and divergence. Whereas mammalian TLRs directly recognize microbial ligands, Drosophila Tolls bind endogenous ligands downstream of both developmental and immune signaling cascades. This study found that most Toll genes in Drosophila evolve slowly with little gene turnover (gains/losses), consistent with their important roles in development and indirect roles in microbial recognition. In contrast, the Toll-3/4 genes were found to have experienced an unusually rapid rate of gene gains and losses, resulting in lineage-specific Toll-3/4s and vastly different gene repertoires among Drosophila species, from zero copies (e.g., D. mojavensis) to nineteen copies (e.g., D. willistoni). In D. willistoni, strong evidence was found for positive selection in Toll-3/4 genes, localized specifically to an extracellular region predicted to overlap with the binding site of Spatzle, the only known ligand of insect Tolls. However, because Spatzle genes are not experiencing similar selective pressures, it was hypothesize that Toll-3/4s may be rapidly evolving because they bind to a different ligand, akin to TLRs outside of insects. Unlike other Toll genes in D. melanogaster, Toll-3 and Toll-4 have apparently escaped from essential developmental roles. It is proposed that the Toll-3/4 genes represent an exceptionally rapidly evolving lineage of Drosophila Toll genes, which play an unusual, as-yet-undiscovered role in the male germline (Levin, 2017).

    Many ways to make darker flies: Intra- and interspecific variation in Drosophila body pigmentation components

    Body pigmentation is an evolutionarily diversified and ecologically relevant trait with substantial variation within and between species, and important roles in animal survival and reproduction. Insect pigmentation, in particular, provides some of the most compelling examples of adaptive evolution, including its ecological significance and genetic bases. Pigmentation includes multiple aspects of color and color pattern that may vary more or less independently, and can be under different selective pressures. This study decomposed Drosophila thorax and abdominal pigmentation, a valuable eco-evo-devo model, into distinct measurable traits related to color and color pattern. Intra- and interspecific variation for those traits was investigated, and its different sources were assessed. For each body part, overall darkness was measured, as well as four other pigmentation properties distinguishing between background color and color of the darker pattern elements that decorate each body part. By focusing on two standard D. melanogaster laboratory populations, this study showed that pigmentation components vary and covary in distinct manners depending on sex, genetic background, and temperature during development. Studying three natural populations of D. melanogaster along a latitudinal cline and five other Drosophila species, it was shown that evolution of lighter or darker bodies can be achieved by changing distinct component traits. The results paint a much more complex picture of body pigmentation variation than previous studies could uncover, including patterns of sexual dimorphism, thermal plasticity, and interspecific diversity. These findings underscore the value of detailed quantitative phenotyping and analysis of different sources of variation for a better understanding of phenotypic variation and diversification, and the ecological pressures and genetic mechanisms underlying them (Lafuente, 2021).

    A fitness trade-off between seasons causes multigenerational cycles in phenotype and population size

    Although seasonality is widespread and can cause fluctuations in the intensity and direction of natural selection, there is little information about the consequences of seasonal fitness trade-offs for population dynamics. This study exposed populations of Drosophila melanogaster to repeated seasonal changes in resources across 58 generations and used experimental and mathematical approaches to investigate how viability selection on body size in the non-breeding season could affect demography. Opposing seasonal episodes of natural selection on body size were shown to interact with both direct and delayed density dependence to cause populations to undergo predictable multigenerational density cycles. These results provide evidence that seasonality can set the conditions for life-history trade-offs and density dependence, which can, in turn, interact to cause multigenerational population cycles (Betini, 2017).

    A Population Genomic Assessment of Three Decades of Evolution in a Natural Drosophila Population

    Population genetics seeks to illuminate the forces shaping genetic variation, often based on a single snapshot of genomic variation. However, utilizing multiple sampling times to study changes in allele frequencies can help clarify the relative roles of neutral and non-neutral forces on short time scales. This study compares whole-genome sequence variation of recently collected natural population samples of Drosophila melanogaster against a collection made approximately 35 years prior from the same locality-encompassing roughly 500 generations of evolution. The allele frequency changes between these time points would suggest a relatively small local effective population size on the order of 10,000, significantly smaller than the global effective population size of the species. Some loci display stronger allele frequency changes than would be expected anywhere in the genome under neutrality-most notably the tandem paralogs Cyp6a17 and Cyp6a23, which are impacted by structural variation associated with resistance to pyrethroid insecticides. A genome-wide excess of outliers was found for high genetic differentiation between old and new samples, but a larger number of adaptation targets may have affected SNP-level differentiation versus window differentiation. Evidence was found for strengthening latitudinal allele frequency clines: northern-associated alleles have increased in frequency by an average of nearly 2.5% at SNPs previously identified as clinal outliers, but no such pattern is observed at random SNPs. This project underscores the scientific potential of using multiple sampling time points to investigate how evolution operates in natural populations, by quantifying how genetic variation has changed over ecologically relevant timescales (Lange, 2022).

    Manipulation of feeding regime alters sexual dimorphism for lifespan and reduces sexual conflict in Drosophila melanogaster

    Sexual dimorphism for lifespan (SDL) is widespread, but poorly understood. A leading hypothesis, which was tested in this study, is that strong SDL can reduce sexual conflict by allowing each sex to maximize its sex-specific fitness. Replicated experimental evolution lines of the fruit fly, Drosophila melanogaster, were used that had been maintained for over 360 generations on either unpredictable 'Random' or predictable 'Regular' feeding regimes. This evolutionary manipulation of feeding regime led to robust, enhanced SDL in Random over control, Regular lines. Enhanced SDL was associated with a significant increase in the fitness of focal males, tested with wild-type (WT) females. This was due to sex-specific changes to male life history, manifested as increased early reproductive output and reduced survival. In contrast, focal female fitness, tested with WT males, did not differ across regimes. Hence increased SDL was associated with a reduction in sexual conflict, which increased male fitness and maintained fitness in females. Differences in SDL were not associated with developmental time or developmental survival. Overall, the results showed that the expression of enhanced SDL, resulting from experimental evolution of feeding regimes, was associated with male-specific changes in life history, leading to increased fitness and reduced sexual conflict (Duxbury, 2017).

    Fear creates an Allee effect: experimental evidence from seasonal populations

    Allee effects, a decline in individual fitness at low population size or density, driven by predation can play a strong role in the decline of small populations but are conventionally thought to occur when generalist predators target specific prey (i.e. type II functional response). However, aside from direct consumption, fear of predators could also increase vigilance and reduce time spent foraging as population size decreases, as has been observed in wild mammals living in social groups. To investigate the role of fear on fitness in relation to population density in a species with limited sociality, varying densities of Drosophila melanogaster were exposed to mantid predators either during an experimental breeding season or non-breeding season. The presence of mantids in either season decreased the reproductive performance of individuals but only at low breeding densities, providing evidence for an Allee effect. The experimental results were used to parametrize a mathematical model to examine the population consequences of fear at low densities. Fear tended to destabilize population dynamics and increase the risk of extinction up to sevenfold. The study provides unique experimental evidence that the indirect effects of the presence of predators can cause an Allee effect and has important consequences for understanding of the dynamics of small populations (Elliott, 2017).

    Pleiotropic effects of DDT resistance on male size and behaviour

    Understanding the evolution and spread of insecticide resistance requires knowing the relative fitness of resistant organisms. In the absence of insecticides, resistance is predicted to be costly. The Drosophila melanogaster DDT resistance allele (DDT-R) is associated with a male mating cost. This could be because resistant males are generally smaller, but DDT-R may also alter courtship behaviours. This study tested for body size and courtship effects of DDT-R on mating success in competitive and non-competitive mating trials respectively. Relative aggression was assessed in resistant and susceptible males because aggression can also influence mating success. While the effect of DDT-R on male size partly contributed to reduced mating success, resistant males also had lower rates of courtship and were less aggressive than susceptible males. These differences contribute to the observed DDT-R mating costs. Additionally, these pleiotropic effects of DDT-R are consistent with the history and spread of resistance alleles in nature (Rostant, 2017).

    Perceptive costs of reproduction drive ageing and physiology in male Drosophila

    Costs of reproduction are thought to result from natural selection optimizing organismal fitness within putative physiological constraints. Phenotypic and population genetic studies of reproductive costs are plentiful across taxa, but an understanding of their mechanistic basis would provide important insight into the diversity in life-history traits, including reproductive effort and ageing. This study dissected the causes and consequences of specific costs of reproduction in male Drosophila melanogaster. Key survival and physiological costs of reproduction arise from perception of the opposite sex, and they are reversed by the act of mating. In the absence of pheromone perception, males are free from reproductive costs on longevity, stress resistance and fat storage. The costs of perception and the benefits of mating are both mediated by evolutionarily conserved neuropeptidergic signalling molecules, as well as the transcription factor dFoxo. These results provide a molecular framework in which certain costs of reproduction arise as a result of self-imposed 'decisions' in response to perceptive neural circuits, which then orchestrate the control of life-history traits independently of physical or energetic effects associated with mating itself (Harvanek, 2017).

    One prophage WO gene rescues cytoplasmic incompatibility in Drosophila melanogaster

    Wolbachia are maternally inherited, intracellular bacteria at the forefront of vector control efforts to curb arbovirus transmission. In international field trials, the cytoplasmic incompatibility (CI) drive system of wMel Wolbachia is deployed to replace target vector populations, whereby a Wolbachia-induced modification of the sperm genome kills embryos. However, Wolbachia in the embryo rescue the sperm genome impairment, and therefore CI results in a strong fitness advantage for infected females that transmit the bacteria to offspring. The two genes responsible for the wMel-induced sperm modification of CI, cifA and cifB, were recently identified in the eukaryotic association module of prophage WO, but the genetic basis of rescue is unresolved. This study used transgenic and cytological approaches to demonstrate that maternal cifA expression independently rescues CI and nullifies embryonic death caused by wMel Wolbachia in Drosophila melanogaster. Discovery of cifA as the rescue gene and previously one of two CI induction genes establishes a "Two-by-One" model that underpins the genetic basis of CI. Results highlight the central role of prophage WO in shaping Wolbachia phenotypes that are significant to arthropod evolution and vector control (Shropshire, 2018).

    Mitochondrial DNA fitness depends on nuclear genetic background in Drosophila

    Mitochondrial DNA (mtDNA) has been one of the most extensively studied molecules in ecological, evolutionary and clinical genetics. In its early application in evolutionary genetics, mtDNA was assumed to be a selectively neutral marker conferring negligible fitness consequences for its host. However, this dogma has been overturned in recent years due to now extensive evidence for non-neutral evolutionary dynamics. Since mtDNA proteins physically interact with nuclear proteins to provide the mitochondrial machinery for aerobic ATP production, among other cell functions, co-variation of the respective genes is predicted to affect organismal fitness. To test this hypothesis, an mtDNA-nuclear DNA introgression model was used in Drosophila melanogaster to test the fitness of genotypes in perturbation-reperturbation population cages and in a non-competitive assay for female fecundity. Genotypes consisted of both conspecific and heterospecific mtDNA-nDNA constructs, with either D. melanogaster or D. simulans mtDNAs on two alternative D. melanogaster nuclear backgrounds, to investigate mitonuclear genetic interactions (G x G effects). Considerable variation was found between nuclear genetic backgrounds on the selection of mtDNA haplotypes. In addition, there was variation in the selection on mtDNAs pre- and post- reperturbation, demonstrating overall poor repeatability of selection. There was a strong influence of nuclear background on non-competitive fecundity across all the mtDNA species types (Mossman, 2019).

    Differential impacts of yeasts on feeding behavior and development in larval Drosophila suzukii (Diptera:Drosophilidae)

    Larval Drosophila encounter and feed on a diverse microbial community within fruit. In particular, free-living yeast microbes provide a source of dietary protein critical for development. However, successional changes to the fruit microbial community may alter host quality through impacts on relative protein content or yeast community composition. For many species of Drosophila, fitness benefits from yeast feeding vary between individual yeast species, indicating differences in yeast nutritional quality. To better understand these associations, this study evaluated how five species of yeast impacted feeding preference and development in larval Drosophila suzukii. Larvae exhibited a strong attraction to the yeast Hanseniaspora uvarum in pairwise yeast feeding assays. However, larvae also performed most poorly on diets containing H. uvarum, a mismatch in preference and performance that suggests differences in yeast nutritional quality are not the primary factor driving larval feeding behavior. Together, these results demonstrate that yeast plays a critical role in D. suzukii's ecology and that larvae may have developed specific yeast associations. Further inquiry, including systematic comparisons of Drosophila larval yeast associations more broadly, will be necessary to understand patterns of microbial resource use in larvae of D. suzukii and other frugivorous species (Lewis, 2019).

    Fitness effects but no temperature-mediated balancing selection at the polymorphic Adh gene of Drosophila melanogaster

    Polymorphism in the alcohol dehydrogenase (ADH) protein of Drosophila melanogaster, like genetic variation in many other enzymes, has long been hypothesized to be maintained by a selective trade-off between thermostability and enzyme activity. Two major Adh variants, named Fast and Slow, are distributed along latitudinal clines on several continents. The balancing selection trade-off hypothesis posits that Fast is favored at high latitudes because it metabolizes alcohol faster, whereas Slow is favored at low latitudes because it is more stable at high temperatures. This study use biochemical and physiological assays of precisely engineered genetic variants to directly test this hypothesis. As predicted, the Fast protein has higher catalytic activity than Slow, and both the Fast protein and regulatory variants linked to it confer greater ethanol tolerance on transgenic animals. No evidence was found of a temperature-mediated trade-off: The Fast protein is not less stable or active at high temperatures, and Fast alleles increase ethanol tolerance and survivorship at all temperatures tested. Further, analysis of a population genomic dataset reveals no signature of balancing selection in the Adh gene. These results provide strong evidence against balancing selection driven by a stability/activity trade-off in Adh, and they justify caution about this hypothesis for other enzymes except those for which it has been directly tested. These findings tentatively suggest that environment-specific selection for the Fast allele, coupled with demographic history, may have produced the observed pattern of Adh variation (Siddiq, 2019).

    Fitness consequences of the selfish supergene Segregation Distorter

    Segregation distorters are selfish genetic elements that subvert Mendelian inheritance, for example by destroying gametes that do not carry the distorter. Simple theoretical models predict that distorter alleles will either spread to fixation, or stabilise at some high intermediate frequency. However, many distorters have substantially lower allele frequencies than predicted by simple models, suggesting that key sources of selection remain to be discovered. This study measured the fitness of Drosophila melanogaster adults and juveniles carrying zero, one, or two copies of three different variants of the naturally-occurring supergene Segregation Distorter (SD), in order to investigate why SD alleles remain relatively rare within populations despite being preferentially inherited. First, it was shown that the three SD variants differ in the severity and dominance of the fitness costs they impose on individuals carrying them. Second, SD-carrying parents produced less fit offspring in some crosses, independent of of spring genotype, indicating that SD alleles can have non-genetic, transgenerational costs in addition to their direct costs. Third, it was found that SD carriers sometimes produce a biased offspring sex ratio, perhaps due to off-target effects of SD on the sex chromosomes (Wong, 2019).

    Mother's curse and indirect genetic effects: Do males matter to mitochondrial genome evolution?

    Maternal inheritance of mitochondrial DNA (mtDNA) was originally thought to prevent any response to selection on male phenotypic variation attributable to mtDNA, resulting in a male-biased mtDNA mutation load ("mother's curse"). However, the theory underpinning this claim implicitly assumes that a male's mtDNA has no effect on the fitness of females he comes into contact with. If such "mitochondrially encoded indirect genetics effects" (mtIGEs) do in fact exist, and there is relatedness between the mitochondrial genomes of interacting males and females, male mtDNA-encoded traits can undergo adaptation after all. This possibility was tested using strains of Drosophila melanogaster that differ in their mtDNA. The experiments indicate that female fitness is influenced by the mtDNA carried by males that the females encounter, which could plausibly allow the mitochondrial genome to evolve via kin selection. It is argued that mtIGEs are probably common, and that this might ameliorate or exacerbate mother's curse (Keaney, 2019).

    Distinct nutritional and endocrine regulation of prothoracic gland activities underlies divergent life history strategies in Manduca sexta and Drosophila melanogaster

    Life history trade-offs lead to various strategies that maximize fitness, but the developmental mechanisms underlying these alternative strategies continue to be poorly understood. In insects, trade-offs exist between size and developmental time. Recent studies in the fruit fly Drosophila melanogaster have suggested that the steroidogenic prothoracic glands play a key role in determining the timing of metamorphosis. In this study, the nutrient-dependent growth and transcriptional activation of prothoracic glands were studied in D. melanogaster and the tobacco hornworm Manduca sexta. In both species, minimum viable weight (MVW) was associated with activation of ecdysteroid biosynthesis genes and growth of prothoracic gland cells. However, the timing of MVW attainment in M. sexta is delayed by the presence of the sesquiterpenoid hormone, juvenile hormone (JH), whereas in D. melanogaster it is not. Moreover, in D. melanogaster, the transcriptional regulation of ecdysteroidogenesis becomes nutrient-independent at the MVW/critical weight (CW) checkpoint. In contrast, in M. sexta, starvation consistently reduced transcriptional activation of ecdysteroid biosynthesis genes even after CW attainment, indicating that the nature of CW differs fundamentally between the two species. In D. melanogaster, the prothoracic glands dictate the timing of metamorphosis even in the absence of nutritional inputs, whereas in M. sexta, prothoracic gland activity is tightly coupled to the nutritional status of the body, thereby delaying the onset of metamorphosis before CW attainment. It is proposed that selection for survival under unpredictable nutritional availability leads to the evolution of increased modularity in both morphological and endocrine traits (Xu, 2020).

    Insect pest control programs often use periods of insecticide treatment with intermittent breaks, to prevent fixing of mutations conferring insecticide resistance. Such mutations are typically costly in an insecticide-free environment, and their frequency is determined by the balance between insecticide treatment and cost of resistance. Ace, a key gene in neuronal signaling, is a prominent target of many insecticides and across several species, three amino acid replacements (I161V, G265A, and F330Y) provide resistance against several insecticides. Because temperature disturbs neuronal signaling homeostasis, it was reasoned that the cost of insecticide resistance could be modulated by ambient temperature. Experimental evolution of a natural Drosophila simulans population at hot and cold temperature regimes uncovered a surprisingly strong effect of ambient temperature. In the cold temperature regime, the resistance mutations were strongly counter selected (s = - 0.055), but in a hot environment, the fitness costs of resistance mutations were reduced by almost 50% (s = - 0.031). This unexpected observation is attributed to the advantage of the reduced enzymatic activity of resistance mutations in hot environments. This study shows that fitness costs of insecticide resistance genes are temperature-dependent and suggest that the duration of insecticide-free periods need to be adjusted for different climatic regions to reflect these costs. It is suggested that such environment-dependent fitness effects may be more common than previously assumed and pose a major challenge for modeling climate change (Langmuller, 2020).

    Evolutionary history of MEK1 illuminates the nature of deleterious mutations

    Mutations in signal transduction pathways lead to various diseases including cancers. MEK1 kinase, encoded by the human MAP2K1 gene, is one of the central components of the MAPK pathway and more than a hundred somatic mutations in the MAP2K1 gene were identified in various tumors. Germline mutations deregulating MEK1 also lead to congenital abnormalities, such as the cardiofaciocutaneous syndrome and arteriovenous malformation. Evaluating variants associated with a disease is a challenge, and computational genomic approaches aid in this process. Establishing evolutionary history of a gene improves computational prediction of disease-causing mutations; however, the evolutionary history of MEK1 is not well understood. In this study, by revealing a precise evolutionary history of MEK1, a well-defined dataset of MEK1 metazoan orthologs was construct, that provides sufficient depth to distinguish between conserved and variable amino acid positions. Known and predicted disease-causing and benign mutations were matched to evolutionary changes observed in corresponding amino acid positions and found that all known and many suspected disease-causing mutations are evolutionarily intolerable. Several variants were selected that cannot be unambiguously assessed by automated prediction tools but that are confidently identified as "damaging" by this approach, for experimental validation in Drosophila. In all cases, evolutionary intolerant variants caused increased mortality and severe defects in fruit fly embryos confirming their damaging nature. It is anticipated that this analysis will serve as a blueprint to help evaluate known and novel missense variants in MEK1 and that this approach will contribute to improving automated tools for disease-associated variant interpretation (Andrianova, 2023).

    Purifying selection against spurious splicing signals contributes to the base composition evolution of the polypyrimidine tract

    Among eukaryotes, the major spliceosomal pathway is highly conserved. While long introns may contain additional regulatory sequences, the ones in short introns seem to be nearly exclusively related to splicing. Although these regulatory sequences involved in splicing are well-characterized, little is known about their evolution. At the 3' end of introns, the splice signal nearly universally contains the dimer AG, which consists of purines, and the polypyrimidine tract upstream of this 3' splice signal is characterized by over-representation of pyrimidines. If the over-representation of pyrimidines in the polypyrimidine tract is also due to avoidance of a premature splicing signal, it is hypothesize that AG should be the most under-represented dimer. Through the use of DNA-strand asymmetry patterns, this prediction was confirmed in fruit flies of the genus Drosophila and by comparing the asymmetry patterns to a presumably neutrally evolving region, the selection strength acting on each motif was quantified. Moreover, the inference and simulation method of this study revealed that the best explanation for the base composition evolution of the polypyrimidine tract is the joint action of purifying selection against a spurious 3' splice signal and the selection for pyrimidines. Patterns of asymmetry in other eukaryotes indicate that avoidance of premature splicing similarly affects the nucleotide composition in their polypyrimidine tracts (Yildirim, 2023).

    Combining Metabolomics and Experimental Evolution Reveals Key Mechanisms Underlying Longevity Differences in Laboratory Evolved Drosophila melanogaster Populations

    Experimental evolution with Drosophila melanogaster has been used extensively for decades to study aging and longevity. In recent years, the addition of DNA and RNA sequencing to this framework has allowed researchers to leverage the statistical power inherent to experimental evolution to study the genetic basis of longevity itself. Here, we incorporated metabolomic data into to this framework to generate even deeper insights into the physiological and genetic mechanisms underlying longevity differences in three groups of experimentally evolved D. melanogaster populations with different aging and longevity patterns. Metabolomic analysis found that aging alters mitochondrial metabolism through increased consumption of NAD(+) and increased usage of the TCA cycle. Combining the genomic and metabolomic data produced a list of biologically relevant candidate genes. Among these candidates, significant enrichment was found for genes and pathways associated with neurological development and function, and carbohydrate metabolism. While enrichment for aging canonical genes was not specifically found, neurological dysregulation and carbohydrate metabolism are both known to be associated with accelerated aging and reduced longevity. Taken together, these results provide plausible genetic mechanisms for what might be driving longevity differences in this experimental system. More broadly, these findings demonstrate the value of combining multiple types of omic data with experimental evolution when attempting to dissect mechanisms underlying complex and highly polygenic traits such as aging (Phillips, 2022).

    An investigation of the sex-specific genetic architecture of fitness in Drosophila melanogaster

    In dioecious populations, the sexes employ divergent reproductive strategies to maximize fitness and, as a result, genetic variants can affect fitness differently in males and females. Moreover, recent studies have highlighted an important role of the mating environment in shaping the strength and direction of sex-specific selection. This study measured adult fitness for each sex of 357 lines from the Drosophila Synthetic Population Resource (DSPR) in two different mating environments. The data was analyzed using three different approaches to gain insight into the sex-specific genetic architecture for fitness: classical quantitative genetics, genomic associations, and a mutational burden approach. The quantitative genetics analysis finds that, on average segregating genetic variation in this population has concordant fitness effects both across the sexes and across mating environments. Specific genomic regions with strong associations with either sexually antagonistic (SA) or sexually concordant (SC) fitness effects were not found, yet there is modest evidence of an excess of genomic regions with weak associations, both with SA and SC fitness effects. This examination of mutational burden indicates stronger selection against indels and loss-of-function variants in females than males (Singh, 2023).

    Repeated duplication of Argonaute2 is associated with strong selection and testis specialization in Drosophila

    Argonaute2 (Ago2) is a rapidly evolving nuclease in the Drosophila melanogaster RNA interference (RNAi) pathway that targets viruses and transposable elements in somatic tissues. This study reconstruct the history of Ago2 duplications across the Drosophila obscura group, and patterns of gene expression were used to infer new functional specialization. Some duplications were shown to be old, shared by the entire species group, and losses may be common, including previously undetected losses in the lineage leading to D. pseudoobscura. While the original (syntenic) gene copy has generally retained the ancestral ubiquitous expression pattern, most of the novel Ago2 paralogues have independently specialized to testis-specific expression. Using population genetic analyses, it was shown that most testis-specific paralogues have significantly lower genetic diversity than the genome-wide average. This suggests recent positive selection in three different species, and model-based analyses provide strong evidence of recent hard selective sweeps in or near four of the six D. pseudoobscura Ago2 paralogues. It is speculated that the repeated evolution of testis-specificity in obscura group Ago2 genes, combined with their dynamic turnover and strong signatures of adaptive evolution, may be associated with highly derived roles in the suppression of transposable elements or meiotic drive. This study highlights the lability of RNAi pathways, even within well-studied groups such as Drosophila, and suggests that strong selection may act quickly after duplication in RNAi pathways, potentially giving rise to new and unknown RNAi functions in non-model species (Lewis, 2016).

    Insights into DDT Resistance from the Drosophila melanogaster Genetic Reference Panel

    Insecticide resistance is considered a classic model of microevolution, where a strong selective agent is applied to a large natural population, resulting in a change in frequency of alleles that confer resistance. While many insecticide resistance variants have been characterized at the gene level, they are typically single genes of large effect identified in highly resistant pest species. In contrast, multiple variants have been implicated in DDT resistance in Drosophila melanogaster, however only the Cyp6g1 locus has previously been shown to be relevant to field populations. This study used genome-wide association studies to identify DDT-associated polygenes and used selective sweep analyses to assess their adaptive significance. Two candidate DDT resistance loci were identified and verified. A largely uncharacterized gene, CG10737, has a function in muscles that ameliorates the effects of DDT, while a putative detoxifying P450, Cyp6w1, shows compelling evidence of positive selection (Schmidt, 2017).

    Structural variants and selective sweep foci contribute to insecticide resistance in the Drosophila genetic reference panel

    Patterns of nucleotide polymorphism within populations of Drosophila melanogaster suggest that insecticides have been the selective agents driving the strongest recent bouts of positive selection. However, there is a need to explicitly link selective sweeps to the particular insecticide phenotypes that could plausibly account for the drastic selective responses that are observed in these non-target insects. This study screened the Drosophila Genetic Reference Panel with two common insecticides; malathion (an organophosphate) and permethrin (a pyrethroid). Genome-wide association studies map survival on malathion to the two of the largest sweeps in the D. melanogaster genome; Ace and Cyp6g1. Malathion survivorship also correlates with lines which have high levels of Cyp12d1, Jheh1 and Jheh2 transcript abundance. Permethrin phenotypes map to the largest cluster of P450 genes in the Drosophila genome, however in contrast to a selective sweep driven by insecticide use, the derived allele seems to be associated with susceptibility. These results underscore previous findings that highlight the importance of structural variation to insecticide phenotypes: Cyp6g1 exhibits copy number variation and transposable element insertions, Cyp12d1 is tandemly duplicated, the Jheh loci are associated with a Bari1 transposable element insertion, and a Cyp6a17 deletion is associated with susceptibility (Battlay, 2018).

    Directional selection reduces developmental canalization against genetic and environmental perturbations in Drosophila wings

    Natural selection may enhance or weaken the robustness of phenotypes against genetic or environmental perturbations. However, important aspects of the relationship between adaptive evolution and canalization remain unclear. Recent work showed that the evolution of larger wing size in a high altitude natural population of Drosophila melanogaster was accompanied by decanalized wing development--specifically a loss of robustness to genetic perturbation. But that study did not address environmental robustness, and it compared populations that may have numerous biological differences. This study performed artificial selection on this same trait in D. melanogaster (larger wing length) and directly test whether this directional selection resulted in decanalization. In general, size-selected replicates show greater frequencies of wing defects than control replicates both after mutagenesis (genetic perturbation) and when subjected to high temperature stress (environmental perturbation), although the increase in defect frequency varies importantly among replicates. These results support the hypothesis that directional selection may result in the loss of both genetic and environmental robustness-offering a rare window into the relationship between adaptation and canalization (Groth, 2018).

    Genetic trade-offs between male reproductive traits in Drosophila melanogaster

    In Drosophila melanogaster, males engage in both extensive pre- and post-copulatory competition for the opportunity to mate with females and subsequently sire offspring. The selection pressure for increased male reproductive success has resulted in the evolution of a wide diversity of sexual traits. However, despite strong selection, individuals often exhibit considerable phenotypic variation in the expression of these traits, and it is unclear if any of this variation is owing to underlying genetic trade-offs. Using hemiclonal flies this study examined how male reproductive success covaries with their ability to induce long-term stimulation of oogenesis and oviposition in their mates, and how this relationship may change over time. It was found that males from hemiclone lines with phenotypes that were more successful in a short-term reproductive 'scramble' environment were less effective at stimulating long-term fecundity in females. Furthermore, it was observed that males from hemiclone lines which showed the most improvement over a longer reproductive interaction period also tended to stimulate higher long-term fecundity in females. Together, these results indicate the presence of genetic trade-offs between different male reproductive traits and offer insights into the maintenance of their variation (Filice, 2018).

    Genomic analysis of European Drosophila melanogaster populations reveals longitudinal structure, continent-wide selection, and previously unknown DNA viruses

    Genetic variation is the fuel of evolution, with standing genetic variation especially important for short-term evolution and local adaptation. To date, studies of spatio-temporal patterns of genetic variation in natural populations have been challenging, as comprehensive sampling is logistically difficult, and sequencing of entire populations costly. This study addresses these issues using a collaborative approach, sequencing 48 pooled population samples from 32 locations, and the first continent-wide genomic analysis of genetic variation was performed in European Drosophila melanogaster. These analyses uncover longitudinal population structure, provide evidence for continent-wide selective sweeps, identify candidate genes for local climate adaptation, and document clines in chromosomal inversion and transposable element frequencies. Variation among populations in the composition of the fly microbiome was characterized, and five new DNA viruses were identified in these samples (Kapun, 2020).

    Natural selection on sleep duration in Drosophila melanogaster

    Sleep is ubiquitous across animal species, but why it persists is not well understood. This study observed natural selection act on Drosophila sleep by relaxing bi-directional artificial selection for extreme sleep duration for 62 generations. When artificial selection was suspended, sleep increased in populations previously selected for short sleep. Likewise, sleep decreased in populations previously selected for long sleep when artificial selection was relaxed. The corresponding changes were measured in the allele frequencies of genomic variants responding to artificial selection. The allele frequencies of these variants reversed course in response to relaxed selection, and for short sleepers, the changes exceeded allele frequency changes that would be expected under random genetic drift. These observations suggest that the variants are causal polymorphisms for sleep duration responding to natural selection pressure. These polymorphisms may therefore pinpoint the most important regions of the genome maintaining variation in sleep duration (Souto-Maior, 2020).

    The genetic architecture of temperature adaptation is shaped by population ancestry and not by selection regime

    Understanding the genetic architecture of temperature adaptation is key for characterizing and predicting the effect of climate change on natural populations. One particularly promising approach is Evolve and Resequence, which combines advantages of experimental evolution such as time series, replicate populations, and controlled environmental conditions, with whole genome sequencing. Recent analysis of replicate populations from two different Drosophila simulans founder populations, which were adapting to the same novel hot environment, uncovered very different architectures-either many selection targets with large heterogeneity among replicates or fewer selection targets with a consistent response among replicates. This study exposed the founder population from Portugal to a cold temperature regime. Although almost no selection targets are shared between the hot and cold selection regime, the adaptive architecture was similar. A moderate number was detected of targets under strong selection (19 selection targets, mean selection coefficient = 0.072) and parallel responses in the cold evolved replicates. This similarity across different environments indicates that the adaptive architecture depends more on the ancestry of the founder population than the specific selection regime. These observations will have broad implications for the correct interpretation of the genomic responses to a changing climate in natural populations (Otte, 2021).

    Broad geographic sampling reveals the shared basis and environmental correlates of seasonal adaptation in Drosophila

    To advance understanding of adaptation to temporally varying selection pressures, signatures of seasonal adaptation occurring in parallel among Drosophila melanogaster populations were identified. Specifically, allele frequencies were assessed genome-wide from flies sampled early and late in the growing season from 20 widely dispersed populations. Parallel seasonal allele frequency shifts were identified across North America and Europe, demonstrating that seasonal adaptation is a general phenomenon of temperate fly populations. Seasonally fluctuating polymorphisms are enriched in large chromosomal inversions, and a broad concordance was found between seasonal and spatial allele frequency change. The direction of allele frequency change at seasonally variable polymorphisms can be predicted by weather conditions in the weeks prior to sampling, linking the environment and the genomic response to selection. These results suggest that fluctuating selection is an important evolutionary force affecting patterns of genetic variation in Drosophila (Machado, 2021).

    Allele frequency divergence reveals ubiquitous influence of positive selection in Drosophila

    Resolving the role of natural selection is a basic objective of evolutionary biology. It is generally difficult to detect the influence of selection because ubiquitous non-selective stochastic change in allele frequencies (genetic drift) degrades evidence of selection. As a result, selection scans typically only identify genomic regions that have undergone episodes of intense selection. Yet it seems likely such episodes are the exception; the norm is more likely to involve subtle, concurrent selective changes at a large number of loci. This study developed a new theoretical approach that uncovers a previously undocumented genome-wide signature of selection in the collective divergence of allele frequencies over time. Applying this approach to temporally resolved allele frequency measurements from laboratory and wild Drosophila populations, this study quantified the selective contribution to allele frequency divergence and found that selection has substantial effects on much of the genome. The magnitude of the total selection coefficient (a measure of the combined effects of direct and linked selection) was further quantified at a typical polymorphic locus and found this to be large (of order 1%) even though most mutations are not directly under selection. Sselective allele frequency divergence is substantially elevated at intermediate allele frequencies, which is argued to be most parsimoniously explained by positive-not negative-selection. Thus, in these populations most mutations are far from evolving neutrally in the short term (tens of generations), including mutations with neutral fitness effects, and the result cannot be explained simply as an ongoing purging of deleterious mutations (Bertram, 2021).

    Genomic Assessment of Three Decades of Evolution in a Natural Drosophila Population

    Population genetics seeks to illuminate the forces shaping genetic variation, often based on a single snapshot of genomic variation. However, utilizing multiple sampling times to study changes in allele frequencies can help clarify the relative roles of neutral and non-neutral forces on short time scales. This study compares whole-genome sequence variation of recently collected natural population samples of Drosophila melanogaster against a collection made approximately 35 years prior from the same locality-encompassing roughly 500 generations of evolution. The allele frequency changes between these time points would suggest a relatively small local effective population size on the order of 10,000, significantly smaller than the global effective population size of the species. Some loci display stronger allele frequency changes than would be expected anywhere in the genome under neutrality-most notably the tandem paralogs Cyp6a17 and Cyp6a23, which are impacted by structural variation associated with resistance to pyrethroid insecticides. A genome-wide excess of outliers was found for high genetic differentiation between old and new samples, but a larger number of adaptation targets may have affected SNP-level differentiation versus window differentiation. Evidence was found for strengthening latitudinal allele frequency clines: northern-associated alleles have increased in frequency by an average of nearly 2.5% at SNPs previously identified as clinal outliers, but no such pattern is observed at random SNPs. This project underscores the scientific potential of using multiple sampling time points to investigate how evolution operates in natural populations, by quantifying how genetic variation has changed over ecologically relevant timescales (Lange, 2021).

    Natural variation in the maternal and zygotic mRNA complements of the early embryo in Drosophila melanogaster

    Maternal gene products supplied to the egg during oogenesis drive the earliest events of development in all metazoans. After the initial stages of embryogenesis, maternal transcripts are degraded as zygotic transcription is activated; this is known as the maternal to zygotic transition (MZT). Recently, it has been shown that the expression of maternal and zygotic transcripts have evolved in the Drosophila genus over the course of 50 million years. However, the extent of natural variation of maternal and zygotic transcripts within a species has yet to be determined. This study asked how the maternal and zygotic pools of mRNA vary within and between populations of D. melanogaster. In order to maximize sampling of genetic diversity, African lines of D. melanogaster originating from Zambia as well as DGRP lines originating from North America were chosen for transcriptomic analysis. Generally, it was found that maternal transcripts are more highly conserved, and zygotic transcripts evolve at a higher rate. There is more within-population variation in transcript abundance than between populations, and expression variation is highest post- MZT between African lines. Determining the natural variation of gene expression surrounding the MZT in natural populations of D. melanogaster gives insight into the extent of how a tightly regulated process may vary within a species, the extent of developmental constraint at both stages and on both the maternal and zygotic genomes, and reveals expression changes allowing this species to adapt as it spread across the world (Feitzinger, 2022).

    Rapid evolutionary change, constraints and the maintenance of polymorphism in natural populations of Drosophila melanogaster

    Allele frequencies can shift rapidly within natural populations. Under certain conditions, repeated rapid allele frequency shifts can lead to the long-term maintenance of polymorphism. In recent years, studies of the model insect Drosophila melanogaster have suggested that this phenomenon is more common than previously believed and is often driven by some form of balancing selection, such as temporally fluctuating or sexually antagonistic selection. This study discusses some of the general insights into rapid evolutionary change revealed by large-scale population genomic studies, as well as the functional and mechanistic causes of rapid adaptation uncovered by single-gene studies. As an example of the latter, a regulatory polymorphism of the D. melanogaster fezzik gene is considered. Polymorphism at this site has been maintained at intermediate frequency over an extended period of time. Regular observations from a single population over a period of 7 years revealed significant differences in the frequency of the derived allele and its variance across collections between the sexes. These patterns are highly unlikely to arise from genetic drift alone or from the action of sexually antagonistic or temporally fluctuating selection individually. Instead, the joint action of sexually antagonistic and temporally fluctuating selection can best explain the observed rapid and repeated allele frequency shifts. Temporal studies such as those reviewed here further understanding of how rapid changes in selection can lead to the long-term maintenance of polymorphism as well as improve our knowledge of the forces driving and limiting adaptation in nature (Glaser-Schmitt, 2023).

    Fitness consequences of biochemical adaptation in Drosophila melanogaster populations under simultaneous selection for faster pre-adult development and extended lifespan

    In holometabolous insects like Drosophila melanogaster, critical size is an important time point during larval life, for irreversible commitment to metamorphosis. This study examined the impact of restricted growth duration in terms of selection for faster pre-adult development in Drosophila melanogaster populations which resulted in the evolution of reduced critical size on adult life history traits. Selection for faster pre-adult development resulted in biochemical adaptation in larval physiology with no compromise in major biomolecules at critical size time point. The flies from the selected populations seem to not only commit to metamorphosis on the attainment of critical size but also seem to channelize resources to reproduction as indicated by similar life-time fecundity of critical size (CS) and normal size (NS) flies from selected populations, while the Control CS flies significantly lower life-time fecundity compared to Control NS flies. The flies from selected populations seem to achieve longevity comparable to control flies despite being significantly smaller in size-thus resource constrained due to faster pre-adult development (Sharma, 2021).

    Evidence for a force favoring GC over AT at short intronic sites in Drosophila simulans and Drosophila melanogaster

    Population genetics studies often make use of a class of nucleotide site free from selective pressures, in order to make inferences about population size changes or natural selection at other sites. If such neutral sites can be identified, they offer the opportunity to avoid any confounding effects of selection. This study investigates evolution at putatively neutrally evolving short intronic sites in natural populations of Drosophila melanogaster and Drosophila simulans, in order to understand the properties of spontaneous mutations and the extent of GC-biased gene conversion in these species. Use of data on the genetics of natural populations is advantageous because it integrates information from large numbers of individuals over long timescales. In agreement with direct evidence from observations of spontaneous mutations in Drosophila was found, this study found a bias in the spectrum of mutations toward AT basepairs. In addition, this bias is stronger in the D. melanogaster lineage than in the D. simulans lineage. The evidence for GC-biased gene conversion in Drosophila has been equivocal. This study provides evidence for a weak force favoring GC in both species, which is correlated with the GC content of introns and is stronger in D. simulans than in D. melanogaster (Jackson, 2021).

    Evolution of phenotypic variance in response to a novel hot environment

    Shifts in trait means are widely considered as evidence for adaptive responses, but the impact on phenotypic variance remains largely unexplored. Classic quantitative genetics provides a theoretical framework to predict how selection on phenotypic mean affects the variance. In addition to this indirect effect, it is also possible that the variance of the trait is the direct target of selection, but experimentally characterized cases are rare. Gene expression variance of Drosophila simulans males was studied before and after 100 generations of adaptation to a novel hot laboratory environment. In each of the two independently evolved populations, the variance of 125 and 97 genes was significantly reduced. It is proposed that the drastic loss in environmental complexity from nature to the lab may have triggered selection for reduced variance. The observation that selection could drive changes in the variance of gene expression could have important implications for studies of adaptation processes in natural and experimental populations (Lai, 2021).

    Glue genes are subjected to diverse selective forces during Drosophila development

    Molecular evolutionary studies usually focus on genes with clear roles in adult fitness or on developmental genes expressed at multiple time points during the life of the organism. This study examined the evolutionary dynamics of Drosophila glue genes, a set of eight genes tasked with a singular primary function during a specific developmental stage: the production of glue that allows animal pupa to attach to a substrate for several days during metamorphosis. Using phenotypic assays and available data from transcriptomics, PacBio genomes, and genetic variation from global populations, the selective forces acting on the glue genes within the cosmopolitan D. melanogaster species and its five closely related species, D. simulans, D. sechellia, D. mauritiana, D. yakuba, and D. teissieri were explored. This study observe a three-fold difference in glue adhesion between the least and the most adhesive D. melanogaster strain, indicating a strong genetic component to phenotypic variation. These eight glue genes are among the most highly expressed genes in salivary glands yet they display no notable codon bias. New copies of Sgs3 and Sgs7 are found in D. yakuba and D. teissieri with the Sgs3 coding sequence evolving rapidly after duplication in the D. yakuba branch. Multiple sites along the various glue genes appear to be constrained. Population genetics analysis in D. melanogaster suggests signs of local adaptive evolution for Sgs3, Sgs5 and Sgs5bis and traces of selective sweeps for Sgs1, Sgs3, Sgs7 and Sgs8. This study shows that stage-specific genes can be subjected to various dynamic evolutionary forces (Borne, 2021).

    Unique structure and positive selection promote the rapid divergence of Drosophila Y chromosomes

    Y chromosomes across diverse species convergently evolve a gene-poor, heterochromatic organization enriched for duplicated genes, LTR retrotransposons, and satellite DNA. Sexual antagonism and a loss of recombination play major roles in the degeneration of young Y chromosomes. However, the processes shaping the evolution of mature, already degenerated Y chromosomes are less well-understood. Because Y chromosomes evolve rapidly, comparisons between closely related species are particularly useful. De novo long read assemblies, complemented with cytological validation, were generated to reveal Y chromosome organization in three closely related species of the Drosophila simulans complex, which diverged only 250,000 years ago and share >98% sequence identity. These Y chromosomes were found to be divergent in their organization and repetitive DNA composition, and new Y-linked gene families were discovered whose evolution is driven by both positive selection and gene conversion. These Y chromosomes are also enriched for large deletions, suggesting that the repair of double-strand breaks on Y chromosomes may be biased toward microhomology-mediated end joining over canonical non-homologous end-joining. It is proposed that this repair mechanism contributes to the convergent evolution of Y chromosome organization across organisms (Chang, 2022).

    An analysis of direct and indirect effects in Drosophila melanogaster undergoing a few cycles of experimental evolution for stress-related traits

    The physiological mechanisms underpinning adaptations to starvation and cold stresses have been extensively studied in Drosophila, yet the understanding of correlated changes in stress-related and life-history traits, as well as the energetics of stress tolerance, still remains elusive. To answer the questions empirically in this context, this study allowed D. melanogaster to evolve for either increased starvation or cold tolerance (24-generations / regime) in an experimental evolution system, and examined whether selection of either trait affects un-selected stress trait, as well as the impacts potential changes in life-history and mating success-related traits. The results revealed remarkable changes in starvation/cold tolerance (up to 1.5-fold) as a direct effect of selection, while cold tolerance had been dramatically reduced (1.26-fold) in the starvation tolerant (ST) lines compared to control counterparts, although no such changes were evident in cold-tolerant (CT) lines. ST lines exhibited a higher level of body lipids and a reduced level of trehalose content, while CT lines accumulated a greater levels of body lipid and trehalose contents. Noticeably, it was found that selection for starvation or cold tolerance positively correlates with larval development time, longevity, and copulation duration, indicating that these traits are among the most common targets of selection trajectories shaping stress tolerance. Altogether, this study highlights the complexity of mechanisms evolved in ST lines that contribute to enhanced starvation tolerance, but also negatively impact cold tolerance. Nevertheless, mechanisms forging enhanced cold tolerance in CT lines appear not to target starvation tolerance. Moreover, the parallel changes in life history/mating success traits across stress regimes could indicate some generic pathways evolved in stressful environments, targeting life-history and mating success characteristics to optimize fitness (Aggarwal, 2022).

    Functional divergence of the bag of marbles gene in the Drosophila melanogaster species group

    In Drosophila melanogaster, a key germline stem cell (GSC) differentiation factor, bag of marbles (bam) shows rapid bursts of amino acid fixations between sibling species D. melanogaster and D. simulans, but not in the outgroup species D. ananassae. This study tested the null hypothesis that the bam differentiation function is conserved between D. melanogaster and four additional Drosophila species in the melanogaster species group spanning approximately 30 million years of divergence. Surprisingly, it was demonstrated that bam is not necessary for oogenesis or spermatogenesis in D. teissieri nor is bam necessary for spermatogenesis in D. ananassae. Remarkably bam function may change on a relatively short time scale. Neutral sequence evolution at bam was tested in additional species of Drosophila, and a positive, but not perfect, correlation was found between evidence for positive selection at bam and its essential role in GSC regulation and fertility for both males and females. Further characterization of bam function in more divergent lineages will be necessary to distinguish between the bam critical gametogenesis role being newly derived in D. melanogaster, D. simulans, D. yakuba, and D. ananassae females or it being basal to the genus and subsequently lost in numerous lineages (Bubnell, 2022).

    Enrichment of Hard Sweeps on the X Chromosome in Drosophila melanogaster

    The characteristic properties of the X chromosome, such as male hemizygosity and its unique inheritance pattern, expose it to natural selection in a way that can be different from the autosomes. This study investigated the differences in the tempo and mode of adaptation on the X chromosome and autosomes in a population of Drosophila melanogaster. Specifically, the hypothesis was tested that due to hemizygosity and a lower effective population size on the X, the relative proportion of hard sweeps, which are expected when adaptation is gradual, compared with soft sweeps, which are expected when adaptation is rapid, is greater on the X than on the autosomes. The incidence of hard versus soft sweeps was quantified in North American D. melanogaster population genomic data with haplotype homozygosity statistics and found an enrichment of the proportion of hard versus soft sweeps on the X chromosome compared with the autosomes, confirming predictions was made from simulations. Understanding these differences may enable a deeper understanding of how important phenotypes arise as well as the impact of fundamental evolutionary parameters on adaptation, such as dominance, sex-specific selection, and sex-biased demography (Harris, 2023).

    Evolution under a model of functionally buffered deleterious mutations can lead to positive selection in protein-coding genes

    Selective pressures on DNA sequences often result in departures from neutral evolution that can be captured by the McDonald-Kreitman (MK) test. However, the nature of such selective forces often remains unknown to experimentalists. Amino acid fixations driven by natural selection in protein coding genes are commonly associated with a genetic arms race or changing biological purposes, leading to proteins with new functionality. This study evaluated the expectations of population genetic patterns under a buffering mechanism driving selective amino acids to fixation, which is motivated by an observed phenotypic rescue of otherwise deleterious nonsynonymous substitutions at bag of marbles (bam) and Sex lethal (Sxl) in Drosophila melanogaster. These two genes were shown to experience strong episodic bursts of natural selection potentially due to infections of the endosymbiotic bacteria Wolbachia observed among multiple Drosophila species. Using simulations to implement and evaluate the evolutionary dynamics of a Wolbachia buffering model, it was demonstrated that selectively fixed amino acid replacements will occur, but that the proportion of adaptive amino acid fixations and the statistical power of the MK test to detect the departure from an equilibrium neutral model are both significantly lower than seen for an arms race/change-in-function model that favors proteins with diversified amino acids. The observed selection pattern at bam in a natural population of D. melanogaster was found to be more consistent with an arms race model than with the buffering model (Shen, 2023).

    Starvation selection reduces and delays larval ecdysone production and signaling

    Previous studies have shown that selection for starvation resistance in Drosophila melanogaster results in delayed eclosion and increased adult fat stores. It is assumed that these traits are caused by the starvation selection pressure, but its mechanism is unknown. This study found that starvation-selected (SS) population stores more fat during larval development and has extended larval development and pupal development time. Developmental checkpoints in the third instar associated with ecdysteroid hormone pulses are increasingly delayed. The delay in the late larval period seen in the SS population is indicative of reduced and delayed ecdysone signaling. An enzyme immunoassay for ecdysteroids (with greatest affinity to the metabolically active 20-hydroxyecdysone and the α-ecdysone precursor) confirmed that the SS population had reduced and delayed hormone production compared with that of fed control (FC) flies. Feeding third instar larvae on food supplemented with α-ecdysone partially rescued the developmental delay and reduced subsequent adult starvation resistance. This work suggests that starvation selection causes reduced and delayed production of ecdysteroids in the larval stage and affects the developmental delay phenotype that contributes to subsequent adult fat storage and starvation resistance (Clark, 2023).

    The genetic basis of variation in immune defense against Lysinibacillus fusiformis infection in Drosophila melanogaster

    The genetic causes of phenotypic variation often differ depending on the population examined, particularly if the populations were founded by relatively small numbers of genotypes. Similarly, the genetic causes of phenotypic variation among similar traits (resistance to different xenobiotic compounds or pathogens) may also be completely different or only partially overlapping. Differences in genetic causes for variation in the same trait among populations suggests context dependence for how selection acts on those traits. Similarities in the genetic causes of variation for different traits, on the other hand, suggests pleiotropy which would also influence how natural selection shapes variation in a trait. This study characterized immune defense against a natural Drosophila pathogen, the Gram-positive bacterium Lysinibacillus fusiformis, in three different populations and found almost no overlap in the genetic architecture of variation in survival post infection. However, when comparing these results to a similar experiment with the fungal pathogen, B. bassiana, a convincing shared QTL peak was found for both pathogens. This peak contains the Bomanin cluster of Drosophila immune effectors. Loss of function mutants and RNAi knockdown experiments confirms a role of some of these genes in immune defense against both pathogens. This suggests that natural selection may act on the entire cluster of Bomanin genes (and the linked region under the QTL) or specific peptides for specific pathogens (Smith, 2023).

    Evolutionary adaptation to juvenile malnutrition impacts adult metabolism and impairs adult fitness in Drosophila

    Juvenile undernutrition has lasting effects on adult metabolism of the affected individuals, but it is unclear how adult physiology is shaped over evolutionary time by natural selection driven by juvenile undernutrition. RNAseq, targeted metabolomics, and genomics were combined to study the consequences of evolution under juvenile undernutrition for metabolism of reproductively active adult females of Drosophila melanogaster. Compared to Control populations maintained on standard diet, Selected populations maintained for over 230 generations on a nutrient-poor larval diet evolved major changes in adult gene expression and metabolite abundance, in particular affecting amino acid and purine metabolism. The evolved differences in adult gene expression and metabolite abundance between Selected and Control populations were positively correlated with the corresponding differences previously reported for Selected versus Control larvae. This implies that genetic variants affect both stages similarly. Even when well fed, the metabolic profile of Selected flies resembled that of flies subject to starvation. Finally, selected flies had lower reproductive output than controls even when both were raised under the conditions under which the selected populations evolved. These results imply that evolutionary adaptation to juvenile undernutrition has large pleiotropic consequences for adult metabolism, and that they are costly rather than adaptive for adult fitness. Thus, juvenile and adult metabolism do not appear to evolve independently from each other even in a holometabolous species where the two life stages are separated by a complete metamorphosis (Erkosar, 2023).

    Genomes from historical Drosophila melanogaster specimens illuminate adaptive and demographic changes across more than 200 years of evolution

    The ability to perform genomic sequencing on long-dead organisms is opening new frontiers in evolutionary research. These opportunities are especially notable in the case of museum collections, from which countless documented specimens may now be suitable for genomic analysis-if data of sufficient quality can be obtained. This study reports 25 newly sequenced genomes from museum specimens of the model organism Drosophila melanogaster, including the oldest extant specimens of this species. By comparing historical samples ranging from the early 1800s to 1933 against modern-day genomes, this study documents evolution across thousands of generations, including time periods that encompass the species' initial occupation of northern Europe and an era of rapidly increasing human activity. It was also found that the Lund, Sweden population underwent local genetic differentiation during the early 1800s to 1933 interval (potentially due to drift in a small population) but then became more similar to other European populations thereafter (potentially due to increased migration). Within each century-scale time period, temporal sampling allows documentation of compelling candidates for recent natural selection. In some cases, insights were gained regarding previously implicated selection candidates, such as ChKov1, for which the inferred timing of selection favors the hypothesis of antiviral resistance over insecticide resistance. Other candidates are novel, such as the circadian-related gene Ahcy, which yields a selection signal that rivals that of the DDT resistance gene Cyp6g1. These insights deepen understanding of recent evolution in a model system, and highlight the potential of future museomic studies (Shpak, 2023).

    Genetic Variation in Sexual Size Dimorphism Is Associated with Variation in Sex-Specific Plasticity in Drosophila

    The difference in body size between females and males, or sexual size dimorphism (SSD), is ubiquitous, yet we have a poor understanding of the developmental genetic mechanisms that generate it and how these mechanisms may vary within and among species. Such an understanding of the genetic architecture of SSD is important if we are to evaluate alternative models of SSD evolution, but the genetic architecture is difficult to describe because SSD is a characteristic of populations, not individuals. Here, we overcome this challenge by using isogenic lineages of Drosophila to measure SSD for 196 genotypes. We demonstrate extensive genetic variation for SSD, primarily driven by higher levels of genetic variation for body size among females than among males. While a general increase is observed in SSD with sex-averaged body size (pooling for sex) among lineages, most of the variation in SSD is independent of sex-averaged body size and shows a strong genetic correlation with sex-specific plasticity, such that increased female-biased SSD is associated with increased body size plasticity in females. Our data are consistent with the condition dependence hypothesis of sexual dimorphism and suggest that SSD in Drosophila is a consequence of selection on the developmental genetic mechanisms that regulate the plasticity of body size (Vea, 2023).

    Clinal variation in the temperature and photoperiodic control of reproductive diapause in Drosophila montana females
    Insect adaptation to climatic conditions at different latitudes has required changes in life-history traits linked with survival and reproduction. Several species, including Drosophila montana, show robust latitudinal variation in the critical day length (CDL), below which more than half of the emerging females enter reproductive diapause at a given temperature. This study used a novel approach to find out whether D. montana also shows latitudinal variation in the critical temperature (CTemp), above which the photoperiodic regulation of diapause is disturbed so that the females develop ovaries in daylengths that are far below their CDL. CTemp was estimated for 53 strains from different latitudes on 3 continents after measuring their diapause proportions at a range of temperatures in 12 h daylength (for 29 of the strains also in continuous darkness). In 12 h daylength, CTemp increased towards high latitudes alongside an increase in CDL, and in 3 high-latitude strains diapause proportion exceeded 50 % in all temperatures. In continuous darkness, the diapause proportion was above 50 % in the lowest temperature(s) in only 9 strains, all of which came from high latitudes. In the second part of the study, changes were measured in CTemp and CDL in a selection experiment favouring reproduction in short daylength (photoperiodic selection) and by exercising selection for females that reproduce in LD12:12 at low temperature (photoperiodic and temperature selection). In both experiments selection induced parallel changes in CDL and CTemp, confirming correlations seen between these traits along latitudinal clines. Overall, the findings suggest that selection towards strong photoperiodic diapause and long CDL at high latitudes has decreased the dependency of D. montana diapause on environmental temperature. Accordingly, the prevalence and timing of the diapause of D. montana is likely to be less vulnerable to climate warming in high- than low-latitude populations (Lankinen, 2023).

    Evolution of Metabolome and Transcriptome Supports a Hierarchical Organization of Adaptive Traits

    Most organismal phenotypes have a polygenic basis, which enables adaptive phenotypic responses on ecological time scales. While adaptive phenotypic changes are highly parallel in replicate populations, this does not apply to the contributing loci. In particular for small populations, the same phenotypic shift can be fueled by different sets of alleles at alternative loci (genetic redundancy). Although this phenomenon is empirically well supported, the molecular basis of the genetic redundancy is not yet understood. To fill this gap, this study compared the heterogeneity of the evolutionary transcriptomic and metabolomic response in ten Drosophila simulans populations which evolved parallel high-level phenotypic changes in a novel temperature environment but used different allelic combinations of alternative loci. The metabolome was shown to evolved more parallel than the transcriptome, confirming a hierarchical organization of molecular phenotypes. Different sets of genes responded in each evolved population but led to the enrichment of similar biological functions and a consistent metabolic profile. Since even the metabolomic response was still highly heterogeneous across evolved populations, it is propose that selection may operate on pathways/networks (Lai, 2023).

    Unveiling Subtle Geographical Clines: Phenotypic Effects and Dynamics of Circadian Clock Gene Polymorphisms
    Understanding of the gene regulatory network that constitutes the circadian clock has greatly increased in recent decades, notably due to the use of Drosophila as a model system. In contrast, the analysis of natural genetic variation that enables the robust function of the clock under a broad range of environments has developed more slowly. The current study analyzed comprehensive genome sequencing data from wild European populations of Drosophila, which were densely sampled through time and space. Hundreds of single nucleotide polymorphisms (SNPs) were identified in nine genes associated with the clock, 276 of which exhibited a latitudinal cline in their allele frequencies. While the effect sizes of these clinal patterns were small, indicating subtle adaptations driven by natural selection, they provided important insights into the genetic dynamics of circadian rhythms in natural populations. Nine SNPs in different genes were chosen and their impact on circadian and seasonal phenotypes was assessed by reconstructing outbred populations fixed for either of the SNP alleles, from inbred DGRP strains. The circadian free-running period of the locomotor activity rhythm was affected by an SNP in doubletime (dbt) and eyes absent (Eya). The SNPs in Clock (Clk), Shaggy (Sgg), period (per), and timeless (tim) affected the acrophase. the time period in a cycle during which the cycle crests or peaks. The alleles of the SNP in Eya conferred different levels of diapause and the chill coma recovery response (Khatib, 2023).

    X chromosome drive in a widespread Palearctic woodland fly, Drosophila testacea

    Selfish genes that bias their own transmission during meiosis can spread rapidly in populations, even if they contribute negatively to the fitness of their host. Driving X chromosomes provide a clear example of this type of selfish propagation. These chromosomes have important evolutionary and ecological consequences, and can be found in a broad range of taxa including plants, mammals, and insects. This study reports a new case of X chromosome drive (X drive) in a widespread woodland fly, Drosophila testacea. Males carrying the driving X (SR males) sire 80-100% female offspring, and possess a diagnostic X chromosome haplotype that is perfectly associated with the sex ratio distortion phenotype. The majority of sons produced by SR males are sterile and appear to lack a Y chromosome, suggesting that meiotic defects involving the Y chromosome may underlie X drive in this species. Abnormalities in sperm cysts of SR males reflect that some spermatids are failing to develop properly, confirming that drive is acting during gametogenesis. By screening wild-caught flies using progeny sex ratios and a diagnostic marker, it was demonstrated that the driving X is present in wild populations at a frequency of ~10% and that suppressors of drive are segregating in the same population. The testacea species group appears to be a hotspot for X drive, and D. testacea is a promising model to compare driving X chromosomes in closely related species, some of which may even be younger than the chromosomes themselves (Keais, 2017).

    A Pooled Sequencing Approach Identifies a Candidate Meiotic Driver in Drosophila

    Meiotic drive occurs when a selfish element increases its transmission frequency above the Mendelian ratio by hijacking the asymmetric divisions of female meiosis. New methods to reliably detect meiotic drive are therefore needed, particularly for discovering moderate-strength drivers that are likely to be more prevalent in natural populations than strong drivers. This study reports an efficient method that uses sequencing of large pools of backcross (BC1) progeny to test for deviations from Mendelian segregation genome-wide of single-nucleotide polymorphisms (SNPs) that distinguish the parental strains. Meiotic drive can be detected by a characteristic pattern of decay in distortion of SNP frequencies, caused by recombination unlinking the driver from distal loci. Control crosses allow allele-frequency distortion caused by meiotic drive to be distinguished from distortion resulting from developmental effects. This approach was used to test whether chromosomes with extreme telomere-length differences segregate at Mendelian ratios, as telomeric regions are a potential hotspot for meiotic drive due to their roles in meiotic segregation and multiple observations of high rates of telomere sequence evolution. Using four different pairings of long and short telomere strains, this study found no evidence that extreme telomere-length variation causes meiotic drive in Drosophila. However, one candidate meiotic driver was identified in a centromere-linked region that shows an ~8% increase in transmission frequency, corresponding to a ~54:46 segregation ratio. These results show that candidate meiotic drivers of moderate strength can be readily detected and localized in pools of F1 progeny (Wei, 2017).

    Efficient allelic-drive in Drosophila

    Gene-drive systems developed in several organisms result in super-Mendelian inheritance of transgenic insertions. This study generalizes this "active genetic" approach to preferentially transmit allelic variants (allelic-drive) resulting from only a single or a few nucleotide alterations. Two configurations for allelic-drive were tested: one, copy-cutting, in which a non-preferred allele is selectively targeted for Cas9/guide RNA (gRNA) cleavage, and a more general approach, copy-grafting, that permits selective inheritance of a desired allele located in close proximity to the gRNA cut site. A phenomenon referred to as lethal-mosaicism was investigated that dominantly eliminates NHEJ-induced mutations and favors inheritance of functional cleavage-resistant alleles. These two efficient allelic-drive methods, enhanced by lethal mosaicism and a trans-generational drive process is referred to as "shadow-drive", have broad practical applications in improving health and agriculture and greatly extend the active genetics toolbox (Guichard, 2019).

    Sex-Ratio meiotic drive shapes the evolution of the Y chromosome in Drosophila simulans

    The recent emergence and spread of X-linked segregation distorters - called "Paris" system - in the worldwide species Drosophila simulans has elicited the selection of drive-resistant Y chromosomes. This study investigated the evolutionary history of 386 Y chromosomes originating from 29 population samples collected over a period of twenty years, showing a wide continuum of phenotypes when tested against the Paris distorters, from high sensitivity to complete resistance (males sire approximately 95% to approximately 40% female progeny). Analyzing around 13 kb of Y-linked gene sequences in a representative subset of nine Y chromosomes, only three polymorphic sites resulting in three haplotypes were found. Remarkably, one of the haplotypes is associated with resistance. This haplotype is fixed in all samples from Sub-Saharan Africa, the region of origin of the drivers. Exceptionally, with the spread of the drivers in Egypt and Morocco, it was possible to record the replacement of the sensitive lineage by the resistant haplotype in real time, within only a few years. In addition, in situ hybridization, using satellite DNA probes, was performed on a subset of 21 Y chromosomes from six locations. In contrast to the low molecular polymorphism, this revealed extensive structural variation suggestive of rapid evolution, either neutral or adaptive. Moreover, the results show that intragenomic conflicts can drive astonishingly rapid replacement of Y chromosomes and suggest that the emergence of Paris segregation distorters in East Africa occurred less than half a century ago (Helleu, 2019).

    Chromosomal rearrangements as a source of new gene formation in Drosophila yakuba

    The origins of new genes are among the most fundamental questions in evolutionary biology. Understanding of the ways that new genetic material appears and how that genetic material shapes population variation remains incomplete. De novo genes and duplicate genes are a key source of new genetic material on which selection acts. To better understand the origins of these new gene sequences, this study explored the ways that structural variation might alter expression patterns and form novel transcripts. Evidence is provided that chromosomal rearrangements are a source of novel genetic variation that facilitates the formation of de novo exons in Drosophila. 51 cases were found of de novo exon formation created by chromosomal rearrangements in 14 strains of D. yakuba. These new genes inherit transcription start signals and open reading frames when the 5' end of existing genes are combined with previously untranscribed regions. Such new genes would appear with novel peptide sequences, without the necessity for secondary transitions from non-coding RNA to protein. This mechanism of new peptide formations contrasts with canonical theory of de novo gene progression requiring non-coding intermediaries that must acquire new mutations prior to loss via pseudogenization. Hence, these mutations offer a means to de novo gene creation and protein sequence formation in a single mutational step, answering a long standing open question concerning new gene formation. Gene expression changes were identified for 134 existing genes, indicating that these mutations can alter gene regulation. Population variability for chromosomal rearrangements is considerable, with 2368 rearrangements observed across 14 inbred lines. More rearrangements were identified on the X chromosome than any of the autosomes, suggesting the X is more susceptible to chromosome alterations. Together, these results suggest that chromosomal rearrangements are a source of variation in populations that is likely to be important to explain genetic and therefore phenotypic diversity (Stewart, 2019).

    Fitness consequences of a non-recombining sex-ratio drive chromosome can explain its prevalence in the wild

    Understanding the pleiotropic consequences of gene drive systems on host fitness is essential to predict their spread through a host population. This paper reports a study sex-ratio (SR) X-chromosome drive in the fly Drosophila recens, where SR causes the death of Y-bearing sperm in male carriers. SR males only sire daughters, which all carry SR, thus giving the chromosome a transmission advantage. The prevalence of the SR chromosome appears stable, suggesting pleiotropic costs. It was previously shown that females homozygous for SR are sterile, and this study tests for additional fitness costs of SR. Females heterozygous for SR were found to have reduced fecundity, and male SR carriers were found to have reduced fertility in conditions of sperm competition. Fitness estimates were used to parametrize theoretical models of SR drive, and sthe decrease in fecundity and sperm competition performance were shown to account for the observed prevalence of SR in natural populations. In addition, it was found that the expected equilibrium frequency of the SR chromosome is particularly sensitive to the degree of multiple mating and performance in sperm competition. Together, these data suggest that the mating system of the organism should be carefully considered during the development of gene drive systems (Dyer, 2019).

    A toxin-antidote CRISPR gene drive system for regional population modification

    Engineered gene drives based on a homing mechanism could rapidly spread genetic alterations through a population. However, such drives face a major obstacle in the form of resistance against the drive. In addition, they are expected to be highly invasive. This study introduce the Toxin-Antidote Recessive Embryo (TARE) drive. It functions by disrupting a target gene, forming recessive lethal alleles, while rescuing drive-carrying individuals with a recoded version of the target. Modeling shows that such drives will have threshold-dependent invasion dynamics, spreading only when introduced above a fitness-dependent frequency. A TARE drive is demonstrated in Drosophila with 88-95% transmission by female heterozygotes. This drive was able to spread through a large cage population in just six generations following introduction at 24% frequency without any apparent evolution of resistance. These results suggest that TARE drives constitute promising candidates for the development of effective, flexible, and regionally confinable drives for population modification (Champer, 2020).

    A Protamine Knockdown Mimics the Function of Sd in Drosophila melanogaster

    Segregation Distorter (SD) is an autosomal meiotic drive system found worldwide in natural populations of Drosophila melanogaster This gene complex induces the preferential and nearly exclusive transmission of the SD chromosome in SD/SD(+) males. This selfish propagation occurs through the interplay of the Sd locus, its enhancers and the Rsp(s) locus during spermatid development. The key distorter locus, Sd, encodes a truncated but enzymatically active RanGAP (RanGTPase-activating protein), a key nuclear transport factor in the Ran signaling pathway. When encoded by Sd, RanGAP is mislocalized to the nucleus interior, which then traps Ran inside the nucleus and disrupts nuclear import. As a result of this aberrant nuclear transport, a process known as the histone-to-protamine transition that is required for proper spermatid condensation fails to occur in SD/SD (+) males. In this process, sperm-specific protamine proteins enter the spermatid nucleus and replace the formerly chromatin-complexed histones. Previous work has shown that mutations affecting nuclear import and export can enhance distortion in an SD background, thus verifying that a defect in nuclear transport is responsible for the unequal transmission of chromosomes. This study shows that specifically reducing protamines induces distortion in an SD background, verifying that protamines are transported via the RanGAP/GEF pathway and indicating that E(SD) plays a significant and unique role in the process of distortion (Gingell, 2020).

    Gene drive and resilience through renewal with next generation Cleave and Rescue selfish genetic elements

    Gene drive-based strategies for modifying populations face the problem that genes encoding cargo and the drive mechanism are subject to separation, mutational inactivation, and loss of efficacy. Resilience, an ability to respond to these eventualities in ways that restore population modification with functional genes, is needed for long-term success. This study shows that resilience can be achieved through cycles of population modification with "Cleave and Rescue" (ClvR) selfish genetic elements. ClvR comprises a DNA sequence-modifying enzyme such as Cas9/gRNAs that disrupts endogenous versions of an essential gene and a recoded version of the essential gene resistant to cleavage. ClvR spreads by creating conditions in which those lacking ClvR die because they lack functional versions of the essential gene. Cycles of modification can, in principle, be carried out if two ClvR elements targeting different essential genes are located at the same genomic position, and one of them, ClvR (n+1), carries a Rescue transgene from an earlier element, ClvR (n) ClvR (n+1) should spread within a population of ClvR (n), while also bringing about a decrease in its frequency. To test this hypothesis, it was first shown that multiple ClvRs, each targeting a different essential gene, function when located at a common chromosomal position in Drosophila. It was then shown that when several of these also carry the Rescue from a different ClvR, they spread to transgene fixation in populations fixed for the latter and at its expense. Therefore, genetic modifications of populations can be overwritten with new content, providing an ongoing point of control (Oberhofer, 2020).

    Extensive Recombination Suppression and Epistatic Selection Causes Chromosome-Wide Differentiation of a Selfish Sex Chromosome in Drosophila pseudoobscura

    Sex-Ratio (SR) chromosomes are selfish X-chromosomes that distort Mendelian segregation and are commonly associated with inversions. These chromosomal rearrangements suppress recombination with Standard (ST) X-chromosomes and are hypothesized to maintain multiple alleles important for drive in a single large haplotype. A multifaceted study was conducted of the multiply inverted Drosophila pseudoobscura SR chromosome to understand the evolutionary history, genetic architecture, and present-day dynamics that shape this enigmatic selfish chromosome. The D. pseudoobscura SRchromosome has three non-overlapping inversions: basal, medial, and terminal. 23 of 29 Mb of the D. pseudoobscura XR chromosome arm is highly differentiated between the Standard (ST) and SR arrangements, including a 6.6Mb collinear region between the medial and terminal inversions. Although crossing-over is heavily suppressed on this chromosome arm, it is not completely eliminated, with measured rates indicating recombination suppression alone cannot explain patterns of differentiation or the near-perfect association of the three SR chromosome inversions in nature. The ancient basal and medial inversions of the SR chromosome were demonstrated contain genes sufficient to cause weak drive. In contrast, the younger terminal inversion cannot drive by itself, but contains at least one modifier gene necessary for full manifestation of strong sex chromosome drive. By parameterizing population genetic models for chromosome-wide linkage disequilibrium with the experimental results, it is inferred that strong selection acts to maintain the near-perfect association of SR chromosome inversions in present day populations. It is concluded the combined action of suppressed recombination and strong, ongoing, epistatic selection shape the D. pseudoobscura SR arrangement into a highly differentiated chromosome (Fuller, 2020).

    Satellite DNA-mediated diversification of a sex-ratio meiotic drive gene family in Drosophila

    Sex chromosomes are susceptible to the evolution of selfish meiotic drive elements that bias transmission and distort progeny sex ratios. Conflict between such sex-ratio drivers and the rest of the genome can trigger evolutionary arms races resulting in genetically suppressed 'cryptic' drive systems. The Winters cryptic sex-ratio drive system of Drosophila simulans comprises a driver, Distorter on the X (Dox) and an autosomal suppressor, Not much yang, a retroduplicate of Dox that suppresses via production of endogenous small interfering RNAs (esiRNAs). This study reports that over 22 Dox-like (Dxl) sequences originated, amplified and diversified over the ~250,000-year history of the three closely related species, D. simulans, D. mauritiana and D. sechellia. The Dxl sequences encode a rapidly evolving family of protamines. Dxl copy numbers amplified by ectopic exchange among euchromatic islands of satellite DNAs on the X chromosome and separately spawned four esiRNA-producing suppressors on the autosomes. These results reveal the genomic consequences of evolutionary arms races and highlight complex interactions among different classes of selfish DNAs (Muirhead, 2021).

    Essential and recurrent roles for hairpin RNAs in silencing de novo sex chromosome conflict in Drosophila simulans

    Meiotic drive loci distort the normally equal segregation of alleles, which benefits their own transmission even in the face of severe fitness costs to their host organism. However, relatively little is known about the molecular identity of meiotic drivers, their strategies of action, and mechanisms that can suppress their activity. This study presents data from the fruitfly Drosophila simulans that address these questions. A family of de novo, protamine-derived X-linked selfish genes (the Dox gene family: Distorter on the X-which is found on the X chromosome and kills Y chromosome-bearing sperm) was demonstrated to be silenced by a pair of newly emerged hairpin RNA (hpRNA) small interfering RNA (siRNA)-class loci, Nmy and Tmy. In the w[XD1] genetic background, knockout of nmy derepresses Dox and MDox in testes and depletes male progeny, whereas knockout of tmy causes misexpression of PDox genes and renders males sterile. Importantly, genetic interactions between nmy and tmy mutant alleles reveal that Tmy also specifically maintains male progeny for normal sex ratio. The Dox loci are functionally polymorphic within D. simulans, such that both nmy-associated sex ratio bias and tmy-associated sterility can be rescued by wild-type X chromosomes bearing natural deletions in different Dox family genes. Finally, using tagged transgenes of Dox and PDox2, the first experimental evidence is provided that Dox family genes encode proteins that are strongly derepressed in cognate hpRNA mutants. Altogether, these studies support a model in which protamine-derived drivers and hpRNA suppressors drive repeated cycles of sex chromosome conflict and resolution that shape genome evolution and the genetic control of male gametogenesis (Vedanayagam, 2023).

    TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants
    A major constraint on the evolution of large body sizes in animals is an increased risk of developing cancer. There is no correlation, however, between body size and cancer risk. This lack of correlation is often referred to as 'Peto's Paradox'. This study showed that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 (see Drosophila p53) and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. Furthermore several of the TP53 retrogenes (TP53RTGs) were shown to be transcribed and likely translated. While TP53RTGs do not appear to directly function as transcription factors, they do contribute to the enhanced sensitivity of elephant cells to DNA damage and the induction of apoptosis by regulating activity of the TP53 signaling pathway. These results suggest that an increase in the copy number of TP53 may have played a direct role in the evolution of very large body sizes and the resolution of Peto's paradox in Proboscideans (Sulak, 2016).

    Optimal scaling of critical size for metamorphosis in the genus Drosophila

    Juveniles must reach a critical body size to become a mature adult. Molecular determinants of critical size have been studied, but the evolutionary importance of critical size is still unclear. Using nine fly species, this study showed that interspecific variation in organism size can be explained solely by species-specific critical size. The observed variation in critical size quantitatively agrees with the interspecific scaling relationship predicted by the life history model, which hypothesizes that critical size mediates an energy allocation switch between juvenile and adult tissues. The mechanism underlying critical size scaling is explained by an inverse relationship between growth duration and growth rate, which cancels out their contributions to the final size. Finally, evolutionary changes in growth duration can be traced back to the scaling of ecdysteroid hormone dynamics. It is concluded that critical size adaptively optimizes energy allocation, and has a central role in organism size determination (Hironaka, 2019).

    Sex-dependent and sex-independent regulatory systems of size variation in natural populations

    Size of organs/organisms is a polygenic trait. Many of the growth-regulatory genes constitute conserved growth signaling pathways. However, how these multiple genes are orchestrated at the systems level to attain the natural variation in size including sexual size dimorphism is mostly unknown. This study has taken a multi-layered systems omics approach to study size variation in the Drosophila wing. Expression levels of many critical growth regulators such as Wnt and TGFbeta pathway components were shown to significantly differ between sexes but not between lines exhibiting size differences within each sex, suggesting a primary role of these regulators in sexual size dimorphism. Only a few growth genes including a receptor of steroid hormone ecdysone exhibit association with between-line size differences. In contrast, between-line size variation was found to be largely regulated by genes with a diverse range of cellular functions, most of which have never been implicated in growth. In addition, it was shown that expression quantitative trait loci (eQTLs) linked to these novel growth regulators accurately predict population-wide, between-line wing size variation. In summary, this study unveils differential gene regulatory systems that control wing size variation between and within sexes (Okada, 2019).

    Gene duplications circumvent trade-offs in enzyme function: Insect adaptation to toxic host plants

    Herbivorous insects and their adaptations against plant toxins provide striking opportunities to investigate the genetic basis of traits involved in coevolutionary interactions. Target site insensitivity to cardenolides has evolved convergently across six orders of insects, involving identical substitutions in the Na,K-ATPase gene and repeated convergent gene duplications. The large milkweed bug, Oncopeltus fasciatus, has three copies of the Na,K-ATPase alpha-subunit gene that bear differing numbers of amino acid substitutions in the binding pocket for cardenolides. To analyze the effect of these substitutions on cardenolide resistance and to infer possible trade-offs in gene function, the cardenolide-sensitive Na,K-ATPase of Drosophila melanogaster was expressed in vitro and four distinct combinations were introduced of substitutions observed in the three gene copies of O. fasciatus. With an increasing number of substitutions, the sensitivity of the Na,K-ATPase to a standard cardenolide decreased in a stepwise manner. At the same time, the enzyme's overall activity decreased significantly with increasing cardenolide resistance and only the least substituted mimic of the Na,K-ATPase α1C copy maintained activity similar to the wild-type enzyme. These results suggest that the Na,K-ATPase copies in O. fasciatus have diverged in function, enabling specific adaptations to dietary cardenolides while maintaining the functionality of this critical ion carrier (Dalla, 2016).

    In insect species like Drosophila melanogaster, evolution of increased resistance or evolution of particular traits under specific environmental conditions can lead to energy trade-offs with other crucial life-history traits. Adaptation to cold stress can, in principle, involve modification of reproductive traits and physiological responses. This study has successfully selected replicate populations of Drosophila melanogaster for increased resistance to cold shock for over 33 generations. In these populations, the ability to recover from cold shock, mate, and lay fertile eggs 24 h post cold shock is under selection. To assess life-history cost, egg viability, mating frequency, longevity, lifetime fecundity, adult mortality, larva to adult development time, larvae to adults survival, and body weight were studied in the cold shock selected populations and their controls under two treatments (a) post cold shock and (b) without cold shock. Twenty-four hours post cold shock, the selected population had significantly higher egg viability and mating frequency compared to control populations indicating that they have higher cold shock resistance. Selected populations had significantly longer pre-adult development time compared to their control populations. Females from the selected populations had higher body weight compared to their control populations. However, no significant difference was found between the selected and control populations in longevity, lifetime fecundity, adult mortality, larvae to adults survival, and male body weight under the cold shock or no cold shock treatments. These findings suggest that cold shock selected populations have evolved higher mating frequency and egg viability. However, there is no apparent life-history associated cost with the evolution of egg viability and reproductive performances under the cold stress condition (Singh, 2021).

    Rapid functional and sequence differentiation of a tandemly-repeated species-specific multigene family in Drosophila

    Gene clusters of recently duplicated genes are hotbeds for evolutionary change. However, understanding of how mutational mechanisms and evolutionary forces shape the structural and functional evolution of these clusters is hindered by the high sequence identity among the copies, which typically results in their inaccurate representation in genome assemblies. The presumed testis-specific, chimeric gene Sdic originated and tandemly expanded in Drosophila melanogaster, contributing to increased male-male xion. Using various types of massively parallel sequencing data, the organization, sequence evolution, and functional attributes of the different Sdic copies were examined. By leveraging long-read sequencing data, both copy number and order differences were uncovered from the currently accepted annotation for the Sdic region. Despite evidence for pervasive gene conversion affecting the Sdic copies, signatures of two episodes of diversifying selection were uncovered, that have contributed to the evolution of a variety of C-termini and miRNA binding site compositions. Expression analyses involving RNA-seq datasets from 59 different biological conditions revealed distinctive expression breadths among the copies, with three copies being transcribed in females, opening the possibility to a sexually antagonistic effect. Phenotypic assays using Sdic knock-out strains indicated that should this antagonistic effect exist, it does not compromise female fertility. These results strongly suggest that the genome consolidation of the Sdic gene cluster is more the result of a quick exploration of different paths of molecular tinkering by different copies than a mere dosage increase, which could be a recurrent evolutionary outcome in the presence of persistent sexual selection (Clifton, 2016).

    Transcriptional interference promotes rapid expression divergence of Drosophila nested genes

    Nested genes are the most common form of protein-coding overlap in eukaryotic genomes. Previous studies have shown that nested genes accumulate rapidly over evolutionary time, typically via the insertion of short young duplicate genes into long introns. However, the evolutionary relationship between nested genes remains unclear. This study compare RNA-seq expression profiles of nested, proximal intra-chromosomal, intermediate intra-chromosomal, distant intra-chromosomal, and inter-chromosomal gene pairs in two Drosophila species. Expression profiles of nested genes were found to be more divergent than those of any other class of genes, supporting the hypothesis that concurrent expression of nested genes is deleterious due to transcriptional interference. Further analysis reveals that expression profiles of derived nested genes are more divergent than those of their ancestral un-nested orthologs, which are more divergent than those of un-nested genes with similar genomic features. Thus, gene expression divergence between nested genes is likely caused by selection against nesting of genes with insufficiently divergent expression profiles, as well as by continued expression divergence after nesting. Moreover, expression divergence and sequence evolutionary rates are elevated in young nested genes and reduced in old nested genes, indicating that a burst of rapid evolution occurs after nesting. Together, these findings suggest that similarity between expression profiles of nested genes is deleterious due to transcriptional interference, and that natural selection addresses this problem both by eradicating highly deleterious nestings and by enabling rapid expression divergence of surviving nested genes, thereby quickly limiting or abolishing transcriptional interference (Assis, 2016).

    The goddard and saturn genes are essential for Drosophila male fertility and may have arisen de novo

    New genes arise through a variety of mechanisms, including the duplication of existing genes and the de novo birth of genes from non-coding DNA sequences. While there are numerous examples of duplicated genes with important functional roles, the functions of de novo genes remain largely unexplored. Many newly evolved genes are expressed in the male reproductive tract, suggesting that these evolutionary innovations may provide advantages to males experiencing sexual selection. Using testis-specific RNA interference, 11 putative de novo genes in Drosophila melanogaster for effects on male fertility, and two, goddard and saturn, were identified that are essential for spermatogenesis and sperm function. goddard knockdown males fail to produce mature sperm, while saturn knockdown males produce fewer sperm that function inefficiently once transferred to females. Consistent with a de novo origin, both genes are identifiable only in Drosophila and are predicted to encode proteins with no sequence similarity to any annotated protein. However, since high levels of divergence prevented the unambiguous identification of the non-coding sequences from which each gene arose, saturn and saturn are considered to be putative de novo genes. Within Drosophila, both genes have been lost in certain lineages, but show conserved, male-specific patterns of expression in the species in which they are found. Goddard is consistently found in single-copy and evolves under purifying selection. In contrast, saturn has diversified through gene duplication and positive selection. These data suggest that de novo genes can evolve essential roles in male reproduction (Gubala, 2017).

    Recurrent gene duplication leads to diverse repertoires of centromeric histones in Drosophila species

    Despite their essential role in the process of chromosome segregation in most eukaryotes, centromeric histones show remarkable evolutionary lability. Not only have they been lost in multiple insect lineages, but they have also undergone gene duplication in multiple plant lineages. Based on detailed study of a handful of model organisms including Drosophila melanogaster, centromeric histone duplication is considered to be rare in animals. Using a detailed phylogenomic study, this study found that Cid, the centromeric histone gene, has undergone at least four independent gene duplications during Drosophila evolution. Duplicate Cid genes were found in D. eugracilis (Cid2), in the montium species subgroup (Cid3, Cid4) and in the entire Drosophila subgenus (Cid5). Cid3, Cid4, Cid5 all localize to centromeres in their respective species. Some Cid duplicates are primarily expressed in the male germline. With rare exceptions, Cid duplicates have been strictly retained after birth, suggesting that they perform non-redundant centromeric functions, independent from the ancestral Cid. Indeed, each duplicate encodes a distinct N-terminal tail, which may provide the basis for distinct protein-protein interactions. Finally, it was shown some Cid duplicates evolve under positive selection whereas others do not. Taken together, these results support the hypothesis that Drosophila Cid duplicates have subfunctionalized. Thus, these gene duplications provide an unprecedented opportunity to dissect the multiple roles of centromeric histones (Kursel, 2017).

    Tandem duplications lead to novel expression patterns through exon shuffling in Drosophila yakuba

    One common hypothesis to explain the impacts of tandem duplications is that whole gene duplications commonly produce additive changes in gene expression due to copy number changes. This study used genome wide RNA-seq data from a population sample of Drosophila yakuba to test this 'gene dosage' hypothesis. Little evidence was observed of expression changes in response to whole transcript duplication capturing 5' and 3' UTRs. Among whole gene duplications, evidence was observed that dosage sharing across copies is likely to be common. The lack of expression changes after whole gene duplication suggests that the majority of genes are subject to tight regulatory control and therefore not sensitive to changes in gene copy number. Rather, changes were observed in expression level due to both shuffling of regulatory elements and the creation of chimeric structures via tandem duplication. Additionally, 30 de novo gene structures were observed arising from tandem duplications, 23 of which form with expression in the testes. Thus, the value of tandem duplications is likely to be more intricate than simple changes in gene dosage. The common regulatory effects from chimeric gene formation after tandem duplication may explain their contribution to genome evolution (Rogers, 2017).

    Diverse cis-regulatory mechanisms contribute to expression evolution of tandem gene duplicates

    Pairs of duplicated genes generally display a combination of conserved expression patterns inherited from their unduplicated ancestor and newly acquired domains. However, how the cis-regulatory architecture of duplicated loci evolves to produce these expression patterns is poorly understood. This study directly examined the gene-regulatory evolution of two tandem duplicates, the Drosophila Ly6 genes CG9336 and CG9338, which arose at the base of the drosophilids between 40 and 60 million years ago. Comparing the expression patterns of the two paralogs in four Drosophila species with that of the unduplicated ortholog in the tephritid Ceratitis capitata, they were shown to diverge from each other as well as from the unduplicated ortholog. Moreover, the expression divergence appears to have occurred close to the duplication event and also more recently in a lineage-specific manner. The comparison of the tissue-specific cis-regulatory modules (CRMs) controlling the paralog expression in the four Drosophila species indicates that diverse cis-regulatory mechanisms, including the novel tissue-specific enhancers, differential inactivation, and enhancer sharing, contributed to the expression evolution. This analysis also reveals a surprisingly variable cis-regulatory architecture, in which the CRMs driving conserved expression domains change in number, location, and specificity. Altogether, this study provides a detailed historical account that uncovers a highly dynamic picture of how the paralog expression patterns and their underlying cis-regulatory landscape evolve. It is argued that these findings will encourage studying cis-regulatory evolution at the whole-locus level in order to understand how interactions between enhancers and other regulatory levels shape the evolution of gene expression (Baudouin-Gonzalez, 2017).

    Adaptation of gene loci to heterochromatin in the course of Drosophila evolution is associated with insulator proteins

    Pericentromeric heterochromatin is generally composed of repetitive DNA forming a transcriptionally repressive environment. Dozens of genes were embedded into pericentromeric heterochromatin during evolution of Drosophilidae lineage while retaining activity. However, factors that contribute to insusceptibility of gene loci to transcriptional silencing remain unknown. This study finds that the promoter region of genes that can be embedded in both euchromatin and heterochromatin exhibits a conserved structure throughout the Drosophila phylogeny and carries motifs for binding of certain chromatin remodeling factors, including insulator proteins. Using ChIP-seq data, this study demonstrates that evolutionary gene relocation between euchromatin and pericentric heterochromatin occurred with preservation of sites of insulation of BEAF-32 in evolutionarily distant species, i.e. D. melanogaster and D. virilis. Moreover, promoters of virtually all protein-coding genes located in heterochromatin in D. melanogaster are enriched with insulator proteins BEAF-32, GAF and dCTCF. Applying RNA-seq of a BEAF-32 mutant, this study shows that the impairment of BEAF-32 function has a complex effect on gene expression in D. melanogaster, affecting even those genes that lack BEAF-32 association in their promoters. It is proposed that conserved intrinsic properties of genes, such as sites of insulation near the promoter regions, may contribute to adaptation of genes to the heterochromatic environment and, hence, facilitate the evolutionary relocation of genes loci between euchromatin and heterochromatin (Funikov, 2020).

    Evolved Differences in cis and trans Regulation Between the Maternal and Zygotic mRNA Complements in the Drosophila Embryo

    How gene expression can evolve depends on the mechanisms driving gene expression. Gene expression is controlled in different ways in different developmental stages; this study asked whether different developmental stages show different patterns of regulatory evolution. To explore the mode of regulatory evolution, this study used the early stages of embryonic development controlled by two different genomes, that of the mother and that of the zygote. During embryogenesis in all animals, initial developmental processes are driven entirely by maternally provided gene products deposited into the oocyte. The zygotic genome is activated later, when developmental control is handed off from maternal gene products to the zygote during the maternal-to-zygotic transition. Using hybrid crosses between sister species of Drosophila (D. simulans, D. sechellia, and D. mauritiana) and transcriptomics, this study finds that the regulation of maternal transcript deposition and zygotic transcription evolve through different mechanisms. Patterns of transcript level inheritance in hybrids, relative to parental species, were found to differ between maternal and zygotic transcripts, and maternal transcript levels are more likely to be conserved. Changes in transcript levels occur predominantly through differences in trans regulation for maternal genes, while changes in zygotic transcription occur through a combination of both cis and trans regulatory changes. Differences in the underlying regulatory landscape in the mother and the zygote are likely the primary determinants for how maternal and zygotic transcripts evolve (Cartwright, 2020).

    Widespread cis- and trans-regulatory evolution underlies the origin, diversification, and loss of a sexually dimorphic fruit fly pigmentation trait

    Changes in gene expression are a prominent feature of morphological evolution. These changes occur to hierarchical gene regulatory networks (GRNs) of transcription factor genes that regulate the expression of trait-building differentiation genes. While changes in the expression of differentiation genes are essential to phenotypic evolution, they can be caused by mutations within cis-regulatory elements (CREs) that drive their expression (cis-evolution) or within genes for CRE-interacting transcription factors (trans-evolution). Locating these mutations remains a challenge, especially when experiments are limited to one species that possesses the ancestral or derived phenotype. This study investigated CREs that control the expression of the differentiation genes tan and yellow, the expression of which evolved during the gain, modification, and loss of dimorphic pigmentation among Sophophora fruit flies. These CREs were shown to be necessary components of a pigmentation GRN, as deletion from Drosophila melanogaster (derived dimorphic phenotype) resulted in lost expression and lost male-specific pigmentation. This study evaluated the ability of orthologous CRE sequences to drive reporter gene expression in species with modified (Drosophila auraria), secondarily lost (Drosophila ananassae), and ancestrally absent (Drosophila willistoni) pigmentation. The transgene host frequently determines CRE activity, implicating trans-evolution as a significant factor for this trait's diversity. The gain of dimorphic Bab transcription factor expression as a trans-change contributing to the dimorphic trait was evaluated. The findings suggest an amenability to change for the landscape of trans-regulators and begs for an explanation as to why this is so common compared to the evolution of differentiation gene CREs (Hughes, 2021).

    Inter-embryo gene expression variability recapitulates the hourglass pattern of evo-devo

    The evolution of embryological development has long been characterized by deep conservation. In animal development, the phylotypic stage in mid-embryogenesis is more conserved than either early or late stages among species within the same phylum. Hypotheses to explain this hourglass pattern have focused on purifying the selection of gene regulation. This paper proposes an alternative-genes are regulated in different ways at different stages and have different intrinsic capacities to respond to perturbations on gene expression. To eliminate the influence of natural selection, the expression variability of isogenetic single embryo transcriptomes was quantified throughout fly Drosophila melanogaster embryogenesis. The expression variability is lower at the phylotypic stage, supporting that the underlying regulatory architecture in this stage is more robust to stochastic variation on gene expression. Evidence is presented that the phylotypic stage is also robust to genetic variations on gene expression. Moreover, chromatin regulation appears to play a key role in the variation and evolution of gene expression. It is suggested that a phylum-level pattern of embryonic conservation can be explained by the intrinsic difference of gene regulatory mechanisms in different stages (Liu, 2020).

    Hybrid Incompatibilities and Transgressive Gene Expression Between Two Closely Related Subspecies of Drosophila

    Genome-wide assays of expression between species and their hybrids have identified genes that become either over- or underexpressed relative to the parental species (i.e., transgressive). Transgressive expression in hybrids is of interest because it highlights possible changes in gene regulation linked to hybrid dysfunction. Previous studies in Drosophila that used long-diverged species pairs with complete or nearly complete isolation (i.e., full sterility and partial inviability of hybrids) and high-levels of genome misregulation have found correlations between expression and coding sequence divergence. The work highlighted the possible effects of directional selection driving sequence divergence and transgressive expression. Whether the same is true for taxa at early stages of divergence that have only achieved partial isolation remains untested. This study reanalyzed previously published genome expression data and available genome sequence reads from a pair of partially isolated subspecies of Drosophila to compare expression and sequence divergence. A significant correlation was found in rates of expression and sequence evolution, but no support for directional selection driving transgressive expression in hybrids. Most transgressive genes in hybrids show no differential expression between parental subspecies. SNP data was used to explore the role of stabilizing selection through compensatory mutations. This study also examined possible misregulation through cascade effects that could be driven by interacting gene networks or co-option of off-target cis-regulatory elements (Go, 2020).

    Rapid Evolution of Autosomal Binding Sites of the Dosage Compensation Complex in Drosophila melanogaster and Its Association With Transcription Divergence

    How pleiotropy influences evolution of protein sequence remains unclear. The male-specific lethal (MSL) complex in Drosophila mediates dosage compensation by 2-fold upregulation of the X chromosome in males. Nevertheless, several MSL proteins also bind autosomes and likely perform functions not related to dosage compensation. The evolution of MOF, MSL1, and MSL2 binding sites was studied in Drosophila melanogaster and its close relative Drosophila simulans. Pervasive expansion of the MSL binding sites were found in D. melanogaster, particularly on autosomes. The majority of these newly-bound regions are unlikely to function in dosage compensation and associated with an increase in expression divergence between D. melanogaster and D. simulans. While dosage-compensation related sites show clear signatures of adaptive evolution, these signatures are even more marked among autosomal regions. This study points to an intriguing avenue of investigation of pleiotropy as a mechanism promoting rapid protein sequence evolution (Dai, 2021).

    The hourglass model of evolutionary conservation during embryogenesis extends to developmental enhancers with signatures of positive selection

    Inter-species comparisons of both morphology and gene expression within a phylum have revealed a period in the middle of embryogenesis with more similarity between species compared to earlier and later time-points. This "developmental hourglass" pattern has been observed in many phyla, yet the evolutionary constraints on gene expression, and underlying mechanisms of how this is regulated, remains elusive. Moreover, the role of positive selection on gene regulation in the more diverged earlier and later stages of embryogenesis remains unknown. Using DNase-seq to identify regulatory regions in two distant Drosophila species (D. melanogaster and D. virilis), this study assessed the evolutionary conservation and adaptive evolution of enhancers throughout multiple stages of embryogenesis. This revealed a higher proportion of conserved enhancers at the phylotypic period, providing a regulatory basis for the hourglass expression pattern. Using an in silico mutagenesis approach, signatures of positive selection on developmental enhancers were detected at early and late stages of embryogenesis, with a depletion at the phylotypic period, suggesting positive selection as one evolutionary mechanism underlying the hourglass pattern of animal evolution (Liu, 2021).

    Episodes of Rapid Recovery of the Functional Activity of the ras85D Gene in the Evolutionary History of Phylogenetically Distant Drosophila Species

    As assemblies of genomes of new species with varying degrees of relationship appear, it becomes obvious that structural rearrangements of the genome, such as inversions, translocations, and transposon movements, are an essential and often the main source of evolutionary variation. In this regard, the following questions arise. How conserved are the regulatory regions of genes? Do they have a common evolutionary origin? And how and at what rate is the functional activity of genes restored during structural changes in the promoter region? This article analyzes the evolutionary history of the formation of the regulatory region of the ras85D gene in different lineages of the genus Drosophila, as well as the participation of mobile elements in structural rearrangements and in the replacement of specific areas of the promoter region with those of independent evolutionary origin. In the process, hypotheses were substantiated about the selection of promoter elements from a number of frequently repeated motifs with different degrees of degeneracy in the ancestral sequence, as well as about the restoration of the minimum required set of regulatory sequences using a conversion mechanism or similar (Chekunova, 2021).

    The evolution of ovary-biased gene expression in Hawaiian Drosophila

    With detailed data on gene expression accessible from an increasingly broad array of species, it is possible test the extent to which developmental genetic knowledge from model organisms predicts expression patterns and variation across species. But to know when differences in gene expression across species are significant, it is necessary to first necessary to know how much evolutionary variation in gene expression is expected. This study provides an answer by analyzing RNAseq data across twelve species of Hawaiian Drosophilidae flies, focusing on gene expression differences between the ovary and other tissues. It was shown that over evolutionary time, there exists a cohort of ovary specific genes that is stable and that largely corresponds to described expression patterns from laboratory model Drosophila species. The results also provide a demonstration of the prediction that, as phylogenetic distance increases, variation between species overwhelms variation between tissue types. Using ancestral state reconstruction of expression, the distribution of evolutionary changes in tissue-biased expression are described, and this was used to identify gains and losses of ovary-biased expression across these twelve species. This distribution was used to calculate the evolutionary correlation in expression changes between genes, and to demonstrate that genes with known interactions in D. melanogaster are significantly more correlated in their evolution than genes with no or unknown interactions. Finally, this correlation matrix was used to infer new networks of genes that share evolutionary trajectories, and these results are presented as a dataset of new testable hypotheses about genetic roles and interactions in the function and evolution of the Drosophila ovary (Church, 2023).

    Mode and Tempo of 3D Genome Evolution in Drosophila

    Topologically associating domains (TADs) are thought to play an important role in preventing gene misexpression by spatially constraining enhancer-promoter contacts. The deleterious nature of gene misexpression implies that TADs should, therefore, be conserved among related species. Several early studies comparing chromosome conformation between species reported high levels of TAD conservation; however, more recent studies have questioned these results. Furthermore, recent work suggests that TAD reorganization is not associated with extensive changes in gene expression. This study investigated the evolutionary conservation of TADs among 11 species of Drosophila. Hi-C data was used to identify TADs in each species and employ a comparative phylogenetic approach to derive empirical estimates of the rate of TAD evolution. Surprisingly, it was found that TADs evolve rapidly. However, it was also found that the rate of evolution depends on the chromatin state of the TAD, with TADs enriched for developmentally regulated chromatin evolving significantly slower than TADs enriched for broadly expressed, active chromatin. It was also found that, after controlling for differences in chromatin state, highly conserved TADs do not exhibit higher levels of gene expression constraint. These results suggest that, in general, most TADs evolve rapidly and their divergence is not associated with widespread changes in gene expression. However, higher levels of evolutionary conservation and gene expression constraints in TADs enriched for developmentally regulated chromatin suggest that these TAD subtypes may be more important for regulating gene expression, likely due to the larger number of long-distance enhancer-promoter contacts associated with developmental genes (Torosin, 2022).

    Stochastic Modeling of Gene Expression Evolution Uncovers Tissue- and Sex-Specific Properties of Expression Evolution in the Drosophila Genus

    Gene expression evolution is typically modeled with the stochastic Ornstein-Uhlenbeck (OU) process. It has been suggested that the estimation of within-species variations using replicated data can increase the predictive power of such models, but this hypothesis has not been fully tested. This study developed EvoGeneX, a computationally efficient implementation of the OU-based method that models within-species variation. Using extensive simulations, this study showed that modeling within-species variations and appropriate selection of species improve the performance of the model. Further, to facilitate a comparative analysis of expression evolution, a formal measure of evolutionary expression divergence was introduced for a group of genes using the rate and the asymptotic level of divergence. With these tools in hand, this study performed the first-ever analysis of the evolution of gene expression across different body-parts, species, and sexes of the Drosophila genus. It was observed that genes with adaptive expression evolution tend to be body-part specific, whereas the genes with constrained evolution tend to be shared across body-parts. Among the neutrally evolving gene expression patterns, gonads in both sexes have higher expression divergence relative to other tissues and the male gonads have even higher divergence than the female gonads. Among the evolutionarily constrained genes, the gonads show different divergence patterns, where the male gonads, and not the female gonads, show less constrained divergence than other body-parts. Finally, interesting examples were shown of adaptive expression evolution, including adaptation of odor binding proteins (Pal, 2023).

    Enhancer architecture and chromatin accessibility constrain phenotypic space during Drosophila development

    Developmental enhancers bind transcription factors and dictate patterns of gene expression during development. Their molecular evolution can underlie phenotypical evolution, but the contributions of the evolutionary pathways involved remain little understood. Using mutation libraries in Drosophila melanogaster embryos, this study observed that most point mutations in developmental enhancers led to changes in gene expression levels but rarely resulted in novel expression outside of the native pattern. In contrast, random sequences, often acting as developmental enhancers, drove expression across a range of cell types; random sequences including motifs for transcription factors with pioneer activity acted as enhancers even more frequently. These findings suggest that the phenotypic landscapes of developmental enhancers are constrained by enhancer architecture and chromatin accessibility. It is proposed that the evolution of existing enhancers is limited in its capacity to generate novel phenotypes, whereas the activity of de novo elements is a primary source of phenotypic novelty (Galupa, 2023).

    This study used transgenesis-based mutagenesis and de novo gene synthesis during fly embryogenesis to investigate evolutionary pathways for enhancer activity. Fly development was used to explore how novel patterns of gene expression might appear from either molecular evolution of developmental enhancers or random sequences. Notably, while reporter gene assays and minimal enhancers may not reflect the full regulatory activities of native loci, such an approach allows evaluation of a broad range of 'possible' enhancer variation in a controlled experimental setup, without associated fitness costs and allowing a broader exploration of evolution and development without the complexities and historical contingencies found in nature. Furthermore, using such an assay in a developmental model system, which generates an embryo in 24 h, regulatory activities can be assayed across ~100,000 cells of different lineage origins (Galupa, 2023).

    Using this approach, it was found that most mutations in enhancers led to changes in levels of reporter gene expression, but almost entirely within their native zones of expression, similar to previous studies using transgenic mutagenesis of the Shh enhancer in murine embryos, or the E3N enhancer and the wing spot196 enhancer in fly embryos. Consistent with current results, known phenotypic evolution through nucleotide mutations of standing regulatory elements seems to appear either through changes in the levels or timings of expression within native zones or the loss of regulatory activities. For example, the evolution of pigmentation spots in fly wings occurred via a specific spatial increase in the melanic protein Yellow, which is uniformly expressed at low levels throughout the developing wings of fruit flies. Evolution of other traits such as thoracic ribs in vertebrates, limbs in snakes, pelvic structures in sticklebacks, and seed shattering in rice are all associated with loss of enhancer activity due to internal enhancer mutations. Additionally, mutations have been found to occur less often in functionally constrained regions of the genome, suggesting that mutation bias may reduce the occurrence of deleterious mutations in regulatory regions (Galupa, 2023).

    Consistent with these results, phenotypic novelties underlain by enhancer-associated ectopic gains of expression are reportedly due to transposon mobilization, rearrangements in chromosome topology, or de novo evolution of enhancers from DNA sequences with unrelated or nonregulatory activities (Galupa, 2023).

    Previous studies have explored the potential of random DNA sequences to lead to reporter gene expression, either as enhancers or promoters, especially in cell lines of prokaryotic or eukaryotic origin. These have shown that there is a short (or sometimes null) mutational distance between random sequences and active cis-regulatory elements, which may improve evolvability. This study tested random sequences in a developmental context and found that most showed enhancer activity across several types of tissues and developmental stages. These results are consistent with a study that tested enhancer activity of all 6-mers in developing zebrafish embryos and found a diverse range of expression for ~38% of the sequences at two developmental stages. We observed expression driven by random sequences even in the absence of motifs within their sequence for TFs with pioneering activity. Yet, when such motifs were included, nearly all sequences acted as 'strong' enhancers (leading to high levels of expression), consistent with the 'evolutionary barrier' to the formation of a novel enhancer being lower in regions that already contain motifs for DNA-binding factors, which can 'act cooperatively with newly emerging sites (Galupa, 2023).

    It is interesting to note that, despite the high potential of random sequences to be expressed during development and across cell types, expression prior to gastrulation was never observed; this was not evaluated in the zebrafish study or in other studies. This may be due to the rapid rates of early fruit fly development, in which gene expression patterns are highly dynamic, and cell-fate specifications occur within minutes. As such, there may be extensive regulatory demands placed on transcriptional enhancers, reflected in the clusters of high-affinity binding sites common across early embryonic developmental enhancers as well as their extensive conservation in function and location (Galupa, 2023).

    In the future, it will be interesting to explore how regulatory demands that change across development-such as nuclear differentiation, network cross-talk, and metabolic changes- are reflected in regulatory architectures and their evolvability. The observation that most random sequences led to expression suggests that the potential of any sequence within the genome to drive expression is enormous and thus 'an important playground for creating new regulatory variability and evolutionary innovation (Galupa, 2023).

    This was further supported by the regulatory potential of the genomic sequences that were tested, containing Ubx/Hth motifs; indeed, the results from this work imply that enhancers would more likely evolve from sequences that contain or are biased toward specific motifs (e.g., GATA and Zelda). Perhaps the challenge from an evolutionary perspective has not been what allows expression, but what prevents expression; thus, mechanisms that repress 'spurious' expression might have evolved across genomes. This is in line with propositions that nucleosomal DNA in eukaryotes has evolved to repress transcription, along with transcriptional repressors and other mechanisms such as DNA methylation, as a response (at least partially) to 'the unbearable ease of expression' present in prokaryotes (Galupa, 2023).

    The action of such repressive mechanisms could also explain why mutagenesis of developmental enhancers, which are subject to evolutionary selection, does not easily lead to expression outside their native patterns of expression. In sum, the findings of this study raise exciting questions about the evolution of enhancers and the emergence of novel patterns of expression that may underlie new phenotypes, suggesting an underappreciated role for de novo evolution of enhancers by happenstance. Genetic theories of morphological evolution will benefit from comparing controlled, multi-dimensional laboratory experiments with standing variation; such an integrative approach could provide the frameworks that will facilitate making of both transcriptional and evolutionary predictions (Galupa, 2023).

    One limitation of this study lies on the numbers - this study has tested a significant number of enhancer variants, but it is still possible that ectopic expression would have been captured more frequently had a larger set of enhancer variants been tested. Also, in principle, a higher number of mutations per enhancer could have also enhanced the likelihood of ectopic expression. Previous work from this lab with the E3N enhancer reported that indeed the proportion of lines with ectopic expression increased with the number of mutations (Galupa, 2023).

    However, this increase plateaued around 20%-30% for lines with ~3+ mutations per enhancer and in this study, the number of mutations in the enhancer variants for twiMPE, rhoNEE, and tinB ranges from 1 to 7 mutations, so it would be expected to have captured a number of lines with ectopic expression. Importantly, the assay captures millions of years of variation in a controlled setting decoupled from fitness costs. It is also possible that ectopic expression might be present in developmental stages that were not analyzed. Finally, would the results be different if a different promoter had been used? This was not tested formally, but based on published literature, it is believed that using a different promoter would not have major implications in the results observed. Testing a total of enhancer-promoter combinations in human cells, efficiency of enhancers has been shown to be approximately the same irrespective of the type of promoter used, and a recent combinatorial analysis of 1,000 human promoters and 1,000 human enhancers confirmed that most enhancers activate all promoters by similar amounts (Galupa, 2023).

    These studies, in cell lines, could only address levels of expression, not spatial patterns-but very recently published results from the lab show that developmental promoters in fly embryos can drive a range of outputs but do not affect spatial aspects of expression, only levels (Galupa, 2023).

    Cis-regulatory evolution underlying the changes in wingless expression pattern associated with wing pigmentation of Drosophila

    The co-option of regulatory genes has the potential to play an important role in the evolutionary gain of new traits. However, the changes at the sequence level that underlie such a co-option event are still elusive. This study identified the changes in the cis-regulatory sequence of wingless that caused co-option of wingless and led to its expression in new places in Drosophila guttifera, which has unique pigmentation patterns on its wings. The newly gained function of gene expression activation was acquired evolutionarily via a combination of pre-existing sequences containing a putative binding site for SMAD transcription factors that exhibit an ancestral function in driving expression at crossveins, and a sequence that is specific to the lineage leading to D. guttifera (Karasawa, 2023).

    Genes relocated between Drosophila chromosome arms evolve under relaxed selective constraints relative to non-relocated genes

    Gene duplication creates a second copy of a gene either in tandem to the ancestral locus or dispersed to another chromosomal location. Gene relocations may be as common as canonical dispersed duplications in which both the ancestral and derived copies are retained. Relocated genes appear to be under more selective constraints than the derived copies of canonical duplications, and they are possibly as conserved as single-copy non-relocated genes. To test this hypothesis, comparative genomics, population genetics, gene expression, and functional analyses were combined to assess the selection pressures acting on relocated, duplicated, and non-relocated single-copy genes in Drosophila genomes. Relocated genes were found to evolve faster than single-copy non-relocated genes, and there is no evidence that this faster evolution is driven by positive selection. In addition, relocated genes are less essential for viability and male fertility than single-copy non-relocated genes, suggesting that relocated genes evolve fast because of relaxed selective constraints. However, relocated genes evolve slower than the derived copies of canonical dispersed duplicated genes. We therefore conclude that relocated genes are under more selective constraints than canonical duplicates, but are not as conserved as single-copy non-relocated genes (Hart, 2018).

    Origin, composition, and structure of the supernumerary B chromosome of Drosophila melanogaster

    The number of chromosomes carried by an individual species is one of its defining characteristics. Some species, however, can also carry supernumerary chromosomes referred to as B chromosomes. B chromosomes were recently identified in a laboratory stock of Drosophila melanogaster enabling them to be subjected to extensive molecular analysis. The B chromosomes by pulsed-field gel electrophoresis and determined their composition through next-generation sequencing. Although these B chromosomes carry no known euchromatic sequence, they are rich in transposable elements and long arrays of short nucleotide repeats, the most abundant being the uncharacterized AAGAT satellite repeat. Fluorescent in-situ hybridization on metaphase chromosome spreads revealed this repeat is located on Chromosome 4, strongly suggesting the origin of the B chromosomes is Chromosome 4. Cytological and quantitative comparisons of signal intensity between Chromosome 4 and the B chromosomes supports the hypothesis that the structure of the B chromosome is an isochromosome. Also, the identification is reported of a new B chromosome variant in a related laboratory stock. This B chromosome has a similar repeat signature as the original but is smaller and much less prevalent. Additional stocks with similar genotypes were examined and B chromosomes were found, but these stocks lacked the AAGAT satellite repeat. This molecular characterization of D. melanogaster B chromosomes is the first step towards understanding how supernumerary chromosomes arise from essential chromosomes and what may be necessary for their stable inheritance (Hanlon, 2018).

    Functional interplay between ribosomal protein paralogues in the eRpL22 family in Drosophila melanogaster

    Duplicated ribosomal protein (RP) genes in the Drosophila melanogaster eRpL22 family encode structurally-divergent and differentially-expressed rRNA-binding RPs. eRpL22 is expressed ubiquitously and eRpL22-like expression is tissue-restricted with highest levels in the adult male germline. Paralogue functional equivalence was explored using the GAL4-UAS system for paralogue knockdown or overexpression and a conditional eRpL22-like knockout in a heat- shock flippase/FRT line. Ubiquitous eRpL22 knockdown with Actin-GAL4 resulted in embryonic lethality, confirming eRpL22 essentiality. eRpL22-like knockdown (60%) was insufficient to cause lethality; yet, conditional eRpL22-like knockout at one hour following egg deposition caused lethality within each developmental stage. Therefore, each paralogue is essential. Variation in timing of heat-shock-induced eRpL22-like knockout highlighted early embryogenesis as the critical period where eRpL22-like expression (not compensated for by eRpL22) is required for normal development of several organ systems, including testis development and subsequent sperm production. To determine if eRpL22-like can substitute for eRpL22, Actin-GAL4 for ubiquitous eRpL22 knockdown and eRpL22-like-FLAG (or FLAG-eRpL22: control) overexpression. Emergence of adults demonstrated that ubiquitous eRpL22-like-FLAG or FLAG-eRpL22 expression eliminates embryonic lethality resulting from eRpL22 depletion. Adults rescued by eRpL22-like-FLAG (but not by FLAG-eRpL22) overexpression had reduced fertility and longevity. It is concluded that eRpL22 paralogue roles are not completely interchangeable and include functionally-diverse roles in development and spermatogenesis (Mageeney, 2018).

    The molecular basis for the neofunctionalization of the juvenile hormone esterase duplication in Drosophila

    The Drosophila melanogaster enzymes juvenile hormone esterase (DmJHE) and its duplicate, DmJHEdup, present ideal examples for studying the structural changes involved in the neofunctionalization of enzyme duplicates. DmJHE is a hormone esterase with precise regulation and highly specific activity for its substrate, juvenile hormone. DmJHEdup is an odorant degrading esterase (ODE) responsible for processing various kairomones in antennae. Phylogenetic analysis shows that the JHE lineage predates the hemi/holometabolan split. DmJHE has sufficient substrate promiscuity and activity against odorant esters for a duplicate to evolve a general ODE function against a range of mid-long chain food esters, as is shown in DmJHEdup. Both JHEs showed very similar active sites despite low sequence identity (30%). Both ODEs differed drastically from the JHEs and each other, explaining their complementary substrate ranges. A small number of amino acid changes are identified that may have been involved in the early stages of the neofunctionalization of DmJHEdup. These results provide key insights into the process of neofunctionalization and the structural changes that can be involved (Hopkins, 2019).

    Rapid Cis-Trans Coevolution Driven by a Novel Gene Retroposed from a Eukaryotic Conserved CCR4-NOT Component in Drosophila

    Young, or newly evolved, genes arise ubiquitously across the tree of life, and they can rapidly acquire novel functions that influence a diverse array of biological processes. Previous work identified a young regulatory duplicate gene in Drosophila, Zeus that unexpectedly diverged rapidly from its parent, Caf40, an extremely conserved component in the CCR4-NOT machinery in post-transcriptional and post-translational regulation of eukaryotic cells, and took on roles in the male reproductive system. This neofunctionalization was accompanied by differential binding of the Zeus protein to loci throughout the Drosophila melanogaster genome. However, the way in which new DNA-binding proteins acquire and coevolve with their targets in the genome is not understood. In this study, by comparing Zeus ChIP-Seq data from D. melanogaster and D. simulans to the ancestral Caf40 binding events from D. yakuba, a species that diverged before the duplication event, a dynamic pattern was found in which Zeus binding rapidly coevolved with a previously unknown DNA motif, which was termed Caf40 and Zeus-Associated Motif (CAZAM), under the influence of positive selection. Interestingly, while both copies of Zeus acquired targets at male-biased and testis-specific genes, D. melanogaster and D. simulans proteins have specialized binding on different chromosomes, a pattern echoed in the evolution of the associated motif. Using CRISPR-Cas9-mediated gene knockout of Zeus and RNA-Seq, this study found that Zeus regulated the expression of 661 differentially expressed genes (DEGs). The results suggest that the evolution of young regulatory genes can be coupled to substantial rewiring of the transcriptional networks into which they integrate, even over short evolutionary timescales. These results thus uncover dynamic genome-wide evolutionary processes associated with new genes (Krinsky, 2021).

    Birth-and-death evolution of the fatty acyl-CoA reductase (FAR) gene family and diversification of cuticular hydrocarbon synthesis in Drosophila

    The birth-and-death evolutionary model proposes that some members of a multigene family are phylogenetically stable and persist as a single copy over time whereas other members are phylogenetically unstable and undergo frequent duplication and loss. Functional studies suggest that stable genes are likely to encode essential functions, while rapidly evolving genes reflect phenotypic differences in traits that diverge rapidly among species. One such class of rapidly diverging traits are insect cuticular hydrocarbons (CHCs), which play dual roles in chemical communications as short-range recognition pheromones as well as protecting the insect from desiccation. Insect CHCs diverge rapidly between related species leading to ecological adaptation and/or reproductive isolation. Because the CHC and essential fatty acid biosynthetic pathways share common genes, it was hypothesized that genes involved in the synthesis of CHCs would be evolutionary unstable, while those involved in fatty acid-associated essential functions would be evolutionary stable. To test this hypothesis, the evolutionary history was investigated of the fatty acyl-CoA reductases (FARs) gene family that encodes enzymes in CHC synthesis. A unique dataset was compiled of 200 FAR proteins across 12 Drosophila species. A broad diversity in FAR content was uncovered that is generated by gene duplications, subsequent gene losses, and alternative splicing. FARs expressed in oenocytes and presumably involved in CHC synthesis are more unstable than FARs from other tissues. Taken together, this study provides empirical evidence that a comparative approach investigating the birth-and-death evolution of gene families can identify candidate genes involved in rapidly diverging traits between species (Finet, 2019).

    Recurrent gene co-amplification on Drosophila X and Y chromosomes

    Y chromosomes often contain amplified genes which can increase dosage of male fertility genes and counteract degeneration via gene conversion. This study identified genes with increased copy number on both X and Y chromosomes in various species of Drosophila, a pattern that has previously been associated with sex chromosome drive involving the Slx and Sly gene families in mice. Recurrent X/Y co-amplification appears to be an important evolutionary force that has shaped gene content evolution of sex chromosomes in Drosophila. This study also demonstrates that convergent acquisition and amplification of testis expressed gene families are common on Drosophila sex chromosomes, and especially on recently formed ones, and one putative novel X/Y co-amplification system was carefully characterized. Co-amplification of the S-Lap1/GAPsec gene pair on both the X and the Y chromosome occurred independently several times in members of the D. obscura group, where this normally autosomal gene pair is sex-linked due to a sex chromosome-autosome fusion. Several evolutionary scenarios were explored that would explain this pattern of co-amplification. Investigation of gene expression and short RNA profiles at the S-Lap1/GAPsec system suggest that, like Slx/Sly in mice, these genes may be remnants of a cryptic sex chromosome drive system, however additional transgenic experiments will be necessary to validate this model. Regardless of whether sex chromosome drive is responsible for this co-amplification, the findings suggest that recurrent gene duplications between X and Y sex chromosomes could have a widespread effect on genomic and evolutionary patterns, including the epigenetic regulation of sex chromosomes, the distribution of sex-biased genes, and the evolution of hybrid sterility (Ellison, 2019).

    A burst of genetic innovation in Drosophila actin-related proteins for testis-specific function

    Many cytoskeletal proteins perform fundamental biological processes and are evolutionarily ancient. For example, the superfamily of actin-related proteins (Arps) specialized early in eukaryotic evolution for diverse cellular roles in the cytoplasm and the nucleus. Despite its strict conservation across eukaryotes, this study found that the Arp superfamily has undergone dramatic lineage-specific diversification in Drosophila. Our phylogenomic analyses reveal four independent Arp gene duplications that occurred in the common ancestor of the obscura group of Drosophila and have been mostly preserved in this lineage. All four obscura-specific Arp paralogs are predominantly expressed in the male germline and have evolved under positive selection. We focus the analyses on the divergent Arp2D paralog, which arose via a retroduplication event from Arp2, a component of the Arp2/3 complex that polymerizes branched actin networks. Computational modeling analyses suggests that Arp2D can replace Arp2 in the Arp2/3 complex and bind actin monomers. Together with the signature of positive selection, these findings suggest that Arp2D may augment Arp2's functions in the male germline. Indeed, it was found that Arp2D is expressed during and following male meiosis, where it localizes to distinct locations such as actin cones-specialized cytoskeletal structures that separate bundled spermatids into individual mature sperm. It is hypothesized that this unprecedented burst of genetic innovation in cytoskeletal proteins may have been driven by the evolution of sperm heteromorphism in the obscura group of Drosophila (Schroeder, 2019).

    Expansion of imaginal disc growth factor gene family in diptera reflects the evolution of novel functions

    Imaginal disc growth factors (IDGFs) are a small protein family found in insects. They are related to chitinases and implicated in multiple functions, including cell growth stimulation, antimicrobial activity, insect hemolymph clotting, and maintenance of the extracellular matrix. A number of new IDGFs have been found in several insect species and their detailed phylogenetic analysis provides a good basis for further functional studies. To achieve this goal, Idgf cDNAs were sequenced from several lepidopteran and trichopteran species and the data was supplemented with sequences retrieved from public databases. A comparison of Idgf genes in different species showed that Diptera typically contain several Idgf paralogs with a simple exon-intron structure (2-3 exons), whereas lepidopteran Idgfs appear as a single copy per genome and contain a higher number of exons (around 9). These results show that, while lepidopteran Idgfs, having single orthologs, are characterized by low divergence and stronger purifying selection over most of the molecule, the duplicated Idgf genes in Diptera, Idgf1 and Idgf4, exhibit signs of positive selection. This characterization of IDGF evolution provides the first information on the changes that formed these important molecules (Zurovcova, 2019).

    Ab initio construction and evolutionary analysis of protein-coding gene families with partially homologous relationships: Closely related Drosophila genomes as a case study

    How have genes evolved within a well-known genome phylogeny? Many protein-coding genes should have evolved as a whole at the gene level, and some should have evolved partly through fragments at the subgene level. To comprehensively explore such complex homologous relationships and better understand gene family evolution, in this study, with de novo-identified modules, the subgene units which could consecutively cover proteins within a set of closely related species, a new phylogeny-based approach was applied that considers evolutionary models with partial homology to classify all protein-coding genes in nine Drosophila genomes. Compared with two other popular methods for gene family construction, this approach improved practical gene family classifications with a more reasonable view of homology and provided a much more complete landscape of gene family evolution at the gene and subgene levels. This study found that most expanded gene families might have evolved mainly through module rearrangements rather than gene duplications and mainly generated single-module genes through partial gene duplication, suggesting that there might be pervasive subgene rearrangement in the evolution of protein-coding gene families. The use of a phylogeny-based approach with partial homology to classify and analyze protein-coding gene families may provide a more comprehensive landscape depicting how genes evolve within a well-known genome phylogeny (Han, 2020).

    Run or die in the evolution of new microRNAs - Testing the Red Queen hypothesis on de novo new genes

    The Red Queen hypothesis depicts evolution as the continual struggle to adapt. According to this hypothesis, new genes, especially those originating from non-genic sequences (i.e., de novo genes), are eliminated unless they evolve continually in adaptation to a changing environment. This study analyzed two Drosophila de novo miRNAs that are expressed in a testis-specific manner with very high rates of evolution in their DNA sequence. These miRNAs were knocked out in two sibling species, and their contributions to different fitness components were investigated. It was observed that the fitness contributions of miR-975 in D. simulans seem positive, in contrast to its neutral contributions in D. melanogaster, while miR-983 appears to have negative contributions in both species, as the fitness of the knockout mutant increases. As predicted by the Red Queen hypothesis, the fitness difference of these de novo miRNAs indicates their different fates (Zhao, 2020).

    Structural and functional characterization of a putative de novo gene in Drosophila

    Comparative genomic studies have repeatedly shown that new protein-coding genes can emerge de novo from noncoding DNA. Still unknown is how and when the structures of encoded de novo proteins emerge and evolve. Combining biochemical, genetic and evolutionary analyses, this study elucidated the function and structure of goddard, a gene which appears to have evolved de novo at least 50 million years ago within the Drosophila genus. Previous studies found that goddard is required for male fertility. This study shows that Goddard protein localizes to elongating sperm axonemes and that in its absence, elongated spermatids fail to undergo individualization. Combining modelling, NMR and circular dichroism (CD) data, this study showed that Goddard protein contains a large central α-helix, but is otherwise partially disordered. Similar results were found for Goddard's orthologs from divergent fly species and their reconstructed ancestral sequences. Accordingly, Goddard's structure appears to have been maintained with only minor changes over millions of years (Lange, 2021).

    Functional Diversification, Redundancy and Epistasis among Paralogs of the Drosophila melanogaster Obp50a-d Gene Cluster

    Large multigene families, such as the insect odorant binding proteins (OBPs), are thought to arise through functional diversification after repeated gene duplications. Whereas many OBPs function in chemoreception, members of this family are also expressed in tissues outside chemosensory organs. Paralogs of the Obp50 gene cluster are expressed in metabolic and male reproductive tissues, but their functions and interrelationships remain unknown. This study reports the genetic dissection of four members of the Obp50 cluster, which are in close physical proximity without intervening genes. CRISPR technology was used to excise the entire cluster while introducing a PhiC31 re-integration site to reinsert constructs in which different combinations of the constituent Obp genes were either intact or rendered inactive. Whole transcriptome sequencing was performed and sexually dimorphic changes in transcript abundances ("transcriptional niches") associated with each gene-edited genotype were assessed. Using this approach, it was possible to estimate redundancy, additivity, diversification, and epistasis among Obp50 paralogs. The effects were analyzed of gene editing of this cluster on organismal phenotypes, and a significant skewing was found of sex ratios attributable to Obp50a, and sex-specific effects on starvation stress resistance attributable to Obp50d. Thus, there is functional diversification within the Obp50 cluster with Obp50a contributing to development and Obp50d to stress resistance. The deletion-reinsertion approach applied to the Obp50 cluster provides a general paradigm for the genetic dissection of paralogs of multigene families (Johnstun, 2021).

    Genomic analyses of new genes and their phenotypic effects reveal rapid evolution of essential functions in Drosophila development

    It is a conventionally held dogma that the genetic basis underlying development is conserved in a long evolutionary time scale. Ample experiments based on mutational, biochemical, functional, and complementary knockdown/knockout approaches have revealed the unexpectedly important role of recently evolved new genes in the development of Drosophila. The recent progress in the genome-wide experimental testing of gene effects and improvements in the computational identification of new genes (< 40 million years ago, Mya) open the door to investigate the evolution of gene essentiality with a phylogenetically high resolution. These advancements also raised interesting issues in techniques and concepts related to phenotypic effect analyses of genes, particularly of those that recently originated. This study reports analyses of these issues, including reproducibility and efficiency of knockdown experiment and difference between RNAi libraries in the knockdown efficiency and testing of phenotypic effects. This study reports a large data from knockdowns of 11,354 genes (~75% of the Drosophila melanogaster total genes), including 702 new genes (~66% of the species total new genes that aged < 40 Mya), revealing a similarly high proportion (~32.2%) of essential genes that originated in various Sophophora subgenus lineages and distant ancestors beyond the Drosophila genus. The transcriptional compensation effect from CRISPR knockout were detected for highly similar duplicate copies. Knockout of a few young genes detected analogous essentiality in various functions in development. Taken together, this experimental and computational analyses provide valuable data for detection of phenotypic effects of genes in general and further strong evidence for the concept that new genes in Drosophila quickly evolved essential functions in viability during development (Xia, 2021).

    Rapid evolutionary diversification of the flamenco locus across simulans clade Drosophila species

    Suppression of transposable elements (TEs) is paramount to maintain genomic integrity and organismal fitness. In D. melanogaster, the flamenco locus is a master suppressor of TEs, preventing the mobilization of certain endogenous retrovirus-like TEs from somatic ovarian support cells to the germline. It is transcribed by Pol II as a long (100s of kb), single-stranded, primary transcript, and metabolized into ~24-32 nt Piwi-interacting RNAs (piRNAs) that target active TEs via antisense complementarity. flamenco is thought to operate as a trap, owing to its high content of recent horizontally transferred TEs that are enriched in antisense orientation. Using newly-generated long read genome data, which is critical for accurate assembly of repetitive sequences, it was found that flamenco has undergone radical transformations in sequence content and even copy number across simulans clade Drosophilid species. Drosophila simulans flamenco has duplicated and diverged, and neither copy exhibits synteny with D. melanogaster beyond the core promoter. Moreover, flamenco organization is highly variable across D. simulans individuals. Next, it was found that D. simulans and D. mauritiana flamenco display signatures of a dual-stranded cluster, with ping-pong signals in the testis and/or embryo. This is accompanied by increased copy numbers of germline TEs, consistent with these regions operating as functional dual-stranded clusters. Overall, the physical and functional diversity of flamenco orthologs is testament to the extremely dynamic consequences of TE arms races on genome organization, not only amongst highly related species, but even amongst individuals (Signor, 2023).

    Evidence from Drosophila Supports Higher Duplicability of Faster Evolving Genes

    The faster rate of evolution of duplicated genes relative to singletons has been well documented in multiple lineages. This observation has generally been attributed to a presumed release from constraint following creation of a redundant, duplicate copy. However, it is not obvious that the relationship operates in this direction. An alternative possibility-that the faster rate of evolution predates the duplication event and the observed differences result from a higher propensity to duplicate in fast-evolving genes-has been tested in primates and in insects. However, these studies arrived at different conclusions and clarity is needed on whether these contrasting results relate to differences in methodology or legitimate biological differences between the lineages selected. This study tested whether duplicable genes are faster evolving independent of duplication in the Drosophila lineage; the results support the conclusion that faster evolving genes are more likely to duplicate, in agreement with previous work in primates. These findings indicate that this characteristic of gene duplication is not restricted to a single lineage and has broad implications for the interpretation of the impact of gene duplication. A subset of "singletons" was identified the defy the general trends and appear to be faster evolving. Further investigation implicates homology detection failure and suggests that these may be duplicable genes with unidentifiable paralogs (Vance, 2022).

    Nuclear transport genes recurrently duplicate by means of RNA intermediates in Drosophila but not in other insects

    The nuclear transport machinery is involved in a well-known male meiotic drive system in Drosophila. Fast gene evolution and gene duplications have been major underlying mechanisms in the evolution of meiotic drive systems, and this might include some nuclear transport genes in Drosophila. So, using a comprehensive, detailed phylogenomic study, this study examined 51 insect genomes for the duplication of the same nuclear transport genes. Most of the nuclear transport duplications in Drosophila are of a few classes of nuclear transport genes, RNA mediated and fast evolving. Many pseudogenes for the Ran gene were obtained. Some of the duplicates are relatively young and likely contributing to the turnover expected for genes under strong but changing selective pressures. These duplications are potentially revealing what features of nuclear transport are under selection. Unlike in flies, only a few duplications were found when the Drosophila duplicated nuclear transport genes were studied in dipteran species outside of Drosophila, and none in other insects. These findings strengthen the hypothesis that nuclear transport gene duplicates in Drosophila evolve either as drivers or suppressors of meiotic drive systems or as other male-specific adaptations circumscribed to flies and involving a handful of nuclear transport functions (Mirsalehi, 2021).

    Evolution of olfactory receptors tuned to mustard oils in herbivorous Drosophilidae

    The diversity of herbivorous insects is attributed to their propensity to specialize on toxic plants. In an evolutionary twist, toxins betray the identity of their bearers when herbivores co-opt them as cues for host-plant finding, but the evolutionary mechanisms underlying this phenomenon are poorly understood. This study focused on Scaptomyza flava, an herbivorous drosophilid specialized on isothiocyanate (ITC)-producing (Brassicacales) plants, and identified Or67b paralogs that were triplicated as mustard-specific herbivory evolved. Using in vivo heterologous systems for the expression of olfactory receptors, it was found that S. flava Or67bs, but not the homologs from microbe-feeding relatives, responded selectively to ITCs, each paralog detected different ITC subsets. Consistent with this, S. flava was attracted to ITCs, as was Drosophila melanogaster expressing S. flava Or67b3 in the homologous Or67b olfactory circuit. ITCs were likely co-opted as olfactory attractants through gene duplication and functional specialization (neofunctionalization and subfunctionalization) in S. flava, a recently-derived herbivore (Matsunaga, 2021).

    Dosage sensitivity and exon shuffling shape the landscape of polymorphic duplicates in Drosophila and humans

    Despite polymorphic duplicate genes' importance for the early stages of duplicate gene evolution, they are less studied than old gene duplicates. Two essential questions thus remain poorly addressed: how does dosage sensitivity, imposed by stoichiometry in protein complexes or by X chromosome dosage compensation, affect the emergence of complete duplicate genes? Do introns facilitate intergenic and intragenic chimaerism as predicted by the theory of exon shuffling? This study analysed new data for Drosophila and public data for humans, to characterize polymorphic duplicate genes with respect to dosage, exon-intron structures and allele frequencies. It was found that complete duplicate genes are under dosage constraint induced by protein stoichiometry but potentially tolerated by X chromosome dosage compensation. It was also found that in the intron-rich human genome, gene fusions and intragenic duplications extensively use intronic breakpoints generating in-frame proteins, in accordance with the theory of exon shuffling. Finally, it was found that only a small proportion of complete or partial duplicates are at high frequencies, indicating the deleterious nature of dosage or gene structural changes. Altogether, this study demonstrates how mechanistic factors including dosage sensitivity and exon-intron structure shape the short-term functional consequences of gene duplication (Zhang, 2021).

    A tandem duplication in Drosophila melanogaster shows enhanced expression beyond the gene copy number

    Tandem duplicated genes are common features of genomes, but the phenotypic consequences of their origins are not well understood. It is not known whether a simple doubling of gene expression should be expected, or else some other expression outcome. This study describes an experimental framework using engineered deletions to assess any contribution of locally acting cis- and globally acting trans-regulatory factors to expression interactions of particular tandem duplicated genes. Acsx1L (CG6300) and Acsx1R (CG11659) are tandem duplicates of a putative acyl-CoA synthetase gene found in Drosophila melanogaster. Experimental deletions of the duplicated segments were used to investigate whether the presence of 1 tandem duplicated block influences the expression of its neighbor. Acsx1L, the gene in the left block, shows much higher expression than either its duplicate Acsx1R or the single Acsx1 in Drosophila simulans. Acsx1L expression decreases drastically upon deleting the right-hand duplicated block. Crosses among wildtype and deletion strains show that high tandem expression is primarily due to cis-acting interactions between the duplicated blocks. No effect of these genes on cuticular hydrocarbons was detected. Sequence and phylogenetic analysis suggest that the duplication rose to fixation in D. melanogaster and has been subject to extensive gene conversion. Some strains actually carry 3 tandem copies, yet strains with 3 Acsx1s do not have higher expression levels than strains with 2. Surveys of tandem duplicate expression have typically not found the expected 2-fold increase in expression. This study suggests that cis-regulatory interactions between duplicated blocks could be responsible for this trend (Loehlin, 2022).

    Demographic analyses of a new sample of haploid genomes from a Swedish population of Drosophila melanogaster

    European and African natural populations of Drosophila melanogaster have been the focus of several studies aiming at inferring demographic and adaptive processes based on genetic variation data. However, in these analyses little attention has been given to gene flow between African and European samples. This paper presents a dataset consisting of 14 fully sequenced haploid genomes sampled from a natural population from the northern species range (Umea, Sweden). This new data was co-analyzed with an African population to compare the likelihood of several competing demographic scenarios for European and African populations and shows that gene flow improves the fit of demographic models to data (Kapopoulou, 2020).

    Thoracic underreplication in Drosophila species estimates a minimum genome size and the dynamics of added DNA

    Many cells in the thorax of Drosophila were found to stall during replication, a phenomenon known as underreplication. Unlike underreplication in nuclei of salivary and follicle cells, this stall occurs with less than one complete round of replication. This stall point allows precise estimations of early-replicating euchromatin and late-replicating heterochromatin regions, providing a powerful tool to investigate the dynamics of structural change across the genome. This study measured underreplication in 132 species across the Drosophila genus and leveraged these data to propose a model for estimating the rate at which additional DNA is accumulated as heterochromatin and euchromatin and also predict the minimum genome size for Drosophila. According to comparative phylogenetic approaches, the rates of change of heterochromatin differ strikingly between Drosophila subgenera. Although these subgenera differ in karyotype, there were no differences by chromosome number, suggesting other structural changes may influence accumulation of heterochromatin. Measurements were taken for both sexes, allowing the visualization of genome size and heterochromatin changes for the hypothetical path of XY sex chromosome differentiation. Additionally, the model presented in this study estimates a minimum genome size in Sophophora remarkably close to the smallest insect genome measured to date, in a species over 200 million years diverged from Drosophila (Hjelmen, 2020).

    Long-term exhaustion of the inbreeding load in Drosophila melanogaster

    Inbreeding depression, the decline in fitness of inbred individuals, is a ubiquitous phenomenon of great relevance in evolutionary biology and in the fields of animal and plant breeding and conservation. Inbreeding depression is due to the expression of recessive deleterious alleles that are concealed in heterozygous state in noninbred individuals, the so-called inbreeding load. Genetic purging reduces inbreeding depression by removing these alleles when expressed in homozygosis due to inbreeding. It is generally thought that fast inbreeding (such as that generated by full-sib mating lines) removes only highly deleterious recessive alleles, while slow inbreeding can also remove mildly deleterious ones. However, a question remains regarding which proportion of the inbreeding load can be removed by purging under slow inbreeding in moderately large populations. This study reports results of two long-term slow inbreeding Drosophila experiments (125-234 generations), each using a large population and a number of derived lines with effective sizes about 1000 and 50, respectively. The inbreeding load was virtually exhausted after more than one hundred generations in large populations and between a few tens and over one hundred generations in the lines. This result is not expected from genetic drift alone, and is in agreement with the theoretical purging predictions. Computer simulations suggest that these results are consistent with a model of relatively few deleterious mutations of large homozygous effects and partially recessive gene action (Perez-Pereira, 2021).

    Sustained positive consequences of genetic rescue of fitness and behavioural traits in inbred populations of Drosophila melanogaster

    One solution to alleviate the detrimental genetic effects associated with reductions in population size and fragmentation is to introduce immigrants from other populations. While the effects of this genetic rescue on fitness traits are fairly well known, it is less clear to what extent inbreeding depression and subsequent genetic rescue affect behavioural traits. In this study, replicated crosses between inbred lines of Drosophila melanogaster were performed in order to investigate the effects of inbreeding and genetic rescue on egg-to-adult viability and negative geotaxis behaviour-a locomotor response used to measure, e.g. the effects of physiological ageing. Transgenerational effects of outcrossing were investigated by examining the fitness consequences in both the F(1) and F(4) generation. The majority of inbred lines showed evidence for inbreeding depression for both egg-to-adult viability and behavioural performance (95% and 66% of lines, respectively), with inbreeding depression being more pronounced for viability compared with the locomotor response. Subsequent outcrossing with immigrants led to an alleviation of the negative effects for both viability and geotaxis response resulting in inbred lines being similar to the outbred controls, with beneficial effects persisting from F(1) to F(4). Overall, the results clearly show that genetic rescue can provide transgenerational rescue of small, inbred populations by rapidly improving population fitness components. Thus, this study shows that even the negative effects of inbreeding on behaviour, similar to that of neurodegeneration associated with physiological ageing, can be reversed by genetic rescue (Jorgensen, 2022).

    An empirical evaluation of the estimation of inbreeding depression from molecular markers under suboptimal conditions

    Inbreeding depression (ID), the reduction in fitness due to inbreeding, is typically measured by the regression of the phenotypic values of individuals for a particular trait on their corresponding inbreeding coefficients (F). While genealogical records can provide these coefficients, they may be unavailable or incomplete, making molecular markers a useful alternative. The power to detect ID and its accuracy depend on the variation of F values of individuals, the sample sizes available, and the accuracy in the estimation of individual fitness traits and F values. This study used Drosophila melanogaster to evaluate the effectiveness of molecular markers in estimating ID under suboptimal conditions. Two sets of 100 pairs of unrelated individuals were generated from a large panmictic population, and they were mated for two generations to produce non-inbred and unrelated individuals (F = 0) and inbred individuals (full-sib progeny; F = 0.25). Using these expected genealogical F values, inbreeding depression was calculated for two fitness-related traits, pupae productivity and competitive fitness.The males from 17 non-inbred pairs and 17 inbred pairs were sequenced to obtain their genomic inbreeding coefficients and estimate ID for the two traits. The scenario assumed was rather restrictive in terms of estimation of ID because: (1) the individuals belonged to the same generation of a large panmictic population, leading to low variation in individual F coefficients; (2) the sample sizes were small; and (3) the traits measured depended on both males and females while only males were sequenced. Despite the challenging conditions of this study, it was found that molecular markers provided estimates of ID that were comparable to those obtained from simple pedigree estimations with larger sample sizes. The results therefore suggest that genomic measures of inbreeding are useful to provide estimates of inbreeding depression even under very challenging scenarios (Perez-Pereira, 2023). >

    Low levels of genetic differentiation with isolation by geography and environment in populations of Drosophila melanogaster from across China

    The fruit fly, Drosophila melanogaster, is a model species in evolutionary studies. However, population processes of this species in East Asia are poorly studied. This study examined the population genetic structure of D. melanogaster across China. There were 14 mitochondrial haplotypes with 10 unique ones out of 23 known from around the globe. Pairwise F(ST) values estimated from 15 novel microsatellites ranged from 0 to 0.11, with geographically isolated populations showing the highest level of genetic uniqueness. STRUCTURE analysis identified high levels of admixture at both the individual and population levels. Mantel tests indicated a strong association between genetic distance and geographical distance as well as environmental distance. Full redundancy analysis (RDA) showed that independent effects of environmental conditions and geography accounted for 62.10% and 31.58% of the total explained genetic variance, respectively. When geographic variables were constrained in a partial RDA analysis, the environmental variables bio2 (mean diurnal air temperature range), bio13 (precipitation of the wettest month), and bio15 (precipitation seasonality) were correlated with genetic distance. This study suggests that demographic history, geographical isolation, and environmental factors have together shaped the population genetic structure of D. melanogaster after its introduction into China (Yue, 2021).

    The Integrity of the HMR complex is necessary for centromeric binding and reproductive isolation in Drosophila

    Postzygotic isolation by genomic conflict is a major cause for the formation of species. Despite its importance, the molecular mechanisms that result in the lethality of interspecies hybrids are still largely unclear. The genus Drosophila, which contains over 1600 different species, is one of the best characterized model systems to study these questions. It has been shown that the expression levels of the two hybrid incompatibility factors Hmr and Lhr diverged in the two closely related Drosophila species, D. melanogaster and D. simulans, resulting in an increased level of both proteins in interspecies hybrids. The overexpression of the two proteins also leads to mitotic defects, a misregulation in the expression of transposable elements and decreased fertility in pure species. This work describes a distinct six subunit protein complex containing HMR and LHR and analyse the effect of Hmr mutations on complex integrity and function. These experiments suggest that HMR needs to bring together components of centromeric and pericentromeric chromatin to fulfil its physiological function and to cause hybrid

    Rapid Global Spread of wRi-like Wolbachia across Multiple Drosophila

    Maternally transmitted Wolbachia, Spiroplasma, and Cardinium bacteria are common in insects, but their interspecific spread is poorly understood. Because Wolbachia cannot survive outside host cells, spread between distantly related host species requires horizontal transfers that are presumably rare. This study documents spread of wRi-like Wolbachia among eight highly diverged Drosophila hosts (10-50 million years) over only about 14,000 years (5,000-27,000). Comparing 110 wRi-like genomes, it was found </=0.02% divergence from the wRi variant that spread rapidly through California populations of D. simulans. The hosts include both globally invasive species (D. simulans, D. suzukii, and D. ananassae) and narrowly distributed Australian endemics (D. anomalata and D. pandora). Phylogenetic analyses that include mtDNA genomes indicate introgressive transfer of wRi-like Wolbachia between closely related species D. ananassae, D. anomalata, and D. pandora but no horizontal transmission within species. These analyses suggest D. ananassae as the Wolbachia source for the recent wRi invasion of D. simulans and D. suzukii as the source of Wolbachia in its sister species D. subpulchrella. Although six of these wRi-like variants cause strong cytoplasmic incompatibility, two cause no detectable reproductive effects, indicating that pervasive mutualistic effects complement the reproductive manipulations for which Wolbachia are best known. "Super spreader" variants like wRi may be particularly useful for controlling insect pests and vector-borne diseases with Wolbachia transinfections (Turelli, 2018).

    The fitness of an introgressing haplotype changes over the course of divergence and depends on its size and genomic location

    The genomic era has made clear that introgression, or the movement of genetic material between species, is a common feature of evolution. Examples of both adaptive and deleterious introgression exist in a variety of systems. What is unclear is how the fitness of an introgressing haplotype changes as species diverge or as the size of the introgressing haplotype changes. In a simple model, this study showed that introgression may more easily occur into parts of the genome which have not diverged heavily from a common ancestor. The key insight is that alleles from a shared genetic background are likely to have positive epistatic interactions, increasing the fitness of a larger introgressing block. In regions of the genome where few existing substitutions are disrupted, this positive epistasis can be larger than incompatibilities with the recipient genome. Further, this study showed that early in the process of divergence, introgression of large haplotypes can be favored more than introgression of individual alleles. This model is consistent with observations of a positive relationship between recombination rate and introgression frequency across the genome; however, it generates several novel predictions. First, the model suggests that the relationship between recombination rate and introgression may not exist, or may be negative, in recently diverged species pairs. Furthermore, the model suggests that introgression that replaces existing derived variation will be more deleterious than introgression at sites carrying ancestral variants. These predictions are tested in an example of introgression in Drosophila melanogaster, with some support for both. Finally, the model provides a potential alternative explanation to asymmetry in the direction of introgression, with expectations of higher introgression from rapidly diverged populations into slowly evolving ones (Dagilis, 2023).

    Verster, K. I., Cinege, G., Lipinszki, Z., Magyar, L. B., Kurucz, E., Tarnopol, R. L., Abraham, E., Darula, Z., Karageorgi, M., Tamsil, J. A., Akalu, S. M., Ando, I. and Whiteman, N. K. (2023). Evolution of insect innate immunity through domestication of bacterial toxins. Proc Natl Acad Sci U S A 120(16): e2218334120. PubMed ID: 37036995

    Evolution of insect innate immunity through domestication of bacterial toxins

    Toxin cargo genes are often horizontally transferred by phages between bacterial species and are known to play an important role in the evolution of bacterial pathogenesis. This study shows how these same genes have been horizontally transferred from phage or bacteria to animals and have resulted in novel adaptations. It was discovered that two widespread bacterial genes encoding toxins of animal cells, cytolethal distending toxin subunit B (cdtB) and apoptosis-inducing protein of 56 kDa (aip56), were captured by insect genomes through horizontal gene transfer from bacteria or phages. To study the function of these genes in insects, focus was placed on Drosophila ananassae as a model. In the D. ananassae subgroup species, cdtB and aip56 are present as singular (cdtB) or fused copies (cdtB::aip56) on the second chromosome. cdtB and aip56 genes and encoded proteins were expressed by immune cells, some proteins were localized to the wasp embryo's serosa, and their expression increased following parasitoid wasp infection. Species of the ananassae subgroup are highly resistant to parasitoid wasps, and it was observed that D. ananassae lines carrying null mutations in cdtB and aip56 toxin genes were more susceptible to parasitoids than the wild type. It is concluded that toxin cargo genes were captured by these insects millions of years ago and integrated as novel modules into their innate immune system. These modules now represent components of a heretofore undescribed defense response and are important for resistance to parasitoid wasps. Phage or bacterially derived eukaryotic toxin genes serve as macromutations that can spur the instantaneous evolution of novelty in animals (Verster, 2023).

    Fine scale mapping of genomic introgressions within the Drosophila yakuba clade

    The process of speciation involves populations diverging over time until they are genetically and reproductively isolated. Hybridization between nascent species was long thought to directly oppose speciation. A natural place to look for individuals with admixed ancestry (indicative of introgression) is in regions where species co-occur. In west Africa, D. santomea and D. yakuba hybridize on the island of Sao Tome, while D. yakuba and D. teissieri hybridize on the nearby island of Bioko. This report quantifies the genomic extent of introgression between the three species of the Drosophila yakuba clade (D. yakuba, D. santomea), D. teissieri). The genomes of 86 individuals were sequenced from all three species. A new statistical framework was developed and applied, using a hidden Markov approach, to identify introgression. Introgression was found to have occurred between both species pairs but most introgressed segments are small (on the order of a few kilobases). After ruling out the retention of ancestral polymorphism as an explanation for these similar regions, this study found that the sizes of introgressed haplotypes indicate that genetic exchange is not recent (>1,000 generations ago). It was additionally shown that in both cases, introgression was rarer on X chromosomes than on autosomes which is consistent with sex chromosomes playing a large role in reproductive isolation. Even though the two species pairs have stable contemporary hybrid zones, providing the opportunity for ongoing gene flow, the results indicate that genetic exchange between these species is currently rare (Turissini, 2017).

    A Maladaptive Combination of Traits Contributes to the Maintenance of a Drosophila Hybrid Zone

    Drosophila teissieri and D. yakuba diverged approximately 3 mya and are thought to share a large, ancestral, African range. These species now co-occur in parts of continental Africa and in west Africa on the island of Bioko. While D. yakuba is a human commensal, D. teissieri seems to be associated with Parinari fruits, restricting its range to forests. Genome data indicate introgression, despite no evidence of contemporary hybridization. This study reports the discovery of D. yakuba-D. teissieri hybrids at the interface of secondary forests and disturbed, open habitats on Bioko. Hybrids are the F1 progeny of D. yakuba females and D. teissieri males. At high temperatures like those found on Bioko, D. teissieri females are generally less receptive to mating, and in combination with temperature effects on egg lay and egg-to-adult viability, this decreases the potential for gene flow between female D. teissieri and male D. yakuba relative to the reciprocal cross. Field and laboratory experiments demonstrate that F1 hybrids have a maladaptive combination of D. yakuba behavior and D. teissieri physiology, generating additional barriers to gene flow. Nevertheless, analysis of introgressed and non-introgressed regions of the genome indicate that, while rare, gene flow is relatively recent. These observations identify precise intrinsic and extrinsic factors that, along with hybrid male sterility, limit gene flow and maintain these species. These data contribute to a growing body of literature that suggests the Gulf of Guinea may be a hotspot for hybridization (Cooper, 2018).

    Rapid and predictable evolution of admixed populations between two Drosophila species pairs

    The consequences of hybridization are varied, ranging from the origin of new lineages, introgression of some genes between species, to the extinction of one of the hybridizing species. This study generated replicate admixed populations between two pairs of sister species of Drosophila: D. simulans and D. mauritiana; and D. yakuba and D. santomea. Each pair consisted of a continental species and an island endemic. The admixed populations were maintained by random mating in discrete generations for over 20 generations. Morphological, behavioral, and fitness-related traits from each replicate population were assessed periodically, and genomic DNA was sequenced from the populations at generation 20. For both pairs of species, species-specific traits and their genomes regressed to those of the continental species. A few alleles from the island species persisted, but they tended to be proportionally rare among all sites in the genome and were rarely fixed within the populations. This paucity of alleles from the island species was particularly pronounced on the X-chromosome. These results indicate that nearly all foreign genes were quickly eliminated after hybridization and that selection against the minor species genome might be similar across experimental replicates (Matute, 2019).

    Seminal fluid protein divergence among populations exhibiting postmating prezygotic reproductive isolation

    Despite holding a central role in fertilization, reproductive traits often show elevated rates of evolution and diversification. The rapid evolution of seminal fluid proteins (Sfps) within populations is predicted to cause mis-signalling between the male ejaculate and the female during and after mating resulting in postmating prezygotic (PMPZ) isolation between populations. Crosses between Drosophila montana populations show PMPZ isolation in the form of reduced fertilization success in both noncompetitive and competitive contexts. This study tested whether male ejaculate proteins produced in the accessory glands or ejaculatory bulb differ between populations using liquid chromatography tandem mass spectrometry. More than 150 differentially abundant proteins were found between populations that may contribute to PMPZ isolation, including a number of proteases, peptidases and several orthologues of Drosophila melanogaster Sfps known to mediate fertilization success. Males from the population that elicit the stronger PMPZ isolation after mating with foreign females typically produced greater quantities of Sfps. The accessory glands and ejaculatory bulb show enrichment for different gene ontology (GO) terms and the ejaculatory bulb contributes more differentially abundant proteins. Proteins with a predicted secretory signal evolve faster than nonsecretory proteins. Finally, advantage was taken of quantitative proteomics data for three Drosophila species to determine shared and unique GO enrichments of Sfps between taxa and which potentially mediate PMPZ isolation. This study provides the first high-throughput quantitative proteomic evidence showing divergence of reproductive proteins between populations that exhibit PMPZ isolation (Garlovsky, 2020).

    Widespread introgression across a phylogeny of 155 Drosophila genomes

    Genome-scale sequence data have invigorated the study of hybridization and introgression, particularly in animals. However, outside of a few notable cases, systematic tests for introgression at a larger phylogenetic scale across entire clades are lacking. This study leverage 155 genome assemblies from 149 species to generate a fossil-calibrated phylogeny and conduct multilocus tests for introgression across 9 monophyletic radiations within the genus Drosophila. Using complementary phylogenomic approaches, widespread introgression was identified across the evolutionary history of Drosophila. Mapping gene-tree discordance onto the phylogeny revealed that both ancient and recent introgression has occurred across most of the 9 clades that were examined. These results provide the first evidence of introgression occurring across the evolutionary history of Drosophila and highlight the need to continue to study the evolutionary consequences of hybridization and introgression in this genus and across the tree of life (Suvorov, 2021).

    Interactions between natural selection and recombination shape the genomic landscape of introgression

    Hybridization between lineages that have not reached complete reproductive isolation appears more and more like a common phenomenon. Indeed, speciation genomics studies have now extensively shown that many species' genomes have hybrid ancestry. However, genomic patterns of introgression are often heterogeneous across the genome. In many organisms, a positive correlation between introgression levels and recombination rate has been observed. It is usually explained by the purging of deleterious introgressed material due to incompatibilities. However, the opposite relationship was observed in a North American population of Drosophila melanogaster with admixed European and African ancestry. In order to explore how directional and epistatic selection can impact the relationship between introgression and recombination, forward simulations were performed of whole D. melanogaster genomes reflecting the North American population's history. The results revealed that the simplest models of positive selection often yield negative correlations between introgression and recombination such as the one observed in D. melanogaster. It was also confirmed that incompatibilities tend to produce positive introgression-recombination correlations. And yet, this study has identified parameter space under each model where the predicted correlation is reversed. These findings deepen understanding of the evolutionary forces that may shape patterns of ancestry across genomes, and they strengthen the foundation for future studies aimed at estimating genome-wide parameters of selection in admixed populations (Duranton, 2022).

    Patterns of Population Structure and Introgression Among Recently Differentiated Drosophila melanogaster Populations

    This study examined patterns of population genetic structure, admixture, and the spatial structuring of candidate incompatibility alleles across a global sample, including 223 new accessions, predominantly from remote regions in Southern Africa. Nine major ancestries were identified, six that primarily occur in Africa and one that has not been previously described. Evidence was found for both contemporary and historical admixture between ancestries, with admixture rates varying both within and between continents. For example, while previous work has highlighted an admixture zone between broadly defined African and European ancestries in the Caribbean and southeastern USA, West African ancestry was identified as the most likely African contributor. Moreover, loci showing the strongest signal of introgression between West Africa and the Caribbean/southeastern USA include several genes relating to neurological development and male courtship behavior, in line with previous work showing shared mating behaviors between these regions. Finally, while it was hypothesized that potential incompatibility loci may contribute to population genetic structure across the range of D. melanogaster; these loci are, on average, not highly differentiated between ancestries. This work contributes to understanding of the evolutionary history of a key model system, and provides insight into the partitioning of diversity across its range (Coughlan, 2022).

    Experimental introgression in Drosophila: Asymmetric postzygotic isolation associated with chromosomal inversions and an incompatibility locus on the X chromosome

    Interspecific gene flow (introgression) is an important source of new genetic variation, but selection against it can reinforce reproductive barriers between interbreeding species. This study used an experimental approach to trace the role of chromosomal inversions and incompatibility genes in preventing introgression between two partly sympatric Drosophila virilis group species, D. flavomontana and D. montana. F(1) hybrid females from a cross between D. flavomontana female and D. montana male with the males of the parental species were backcrossed for two generations, and pools of parental strains and their reciprocal second generation backcross (BC(2) mon and BC(2) fla) females were sequenced. Contrasting the observed amount of introgression (mean hybrid index, HI) in BC(2) female pools along the genome to simulations under different scenarios allowed identification of chromosomal regions of restricted and increased introgression. No deviation was found from the HI expected under a neutral null model for any chromosome for the BC(2) mon pool, suggesting no evidence for genetic incompatibilities in backcrosses towards D. montana. In contrast, the BC(2) fla pool showed high variation in the observed HI between different chromosomes, and massive reduction of introgression on the X chromosome (large X-effect). This observation is compatible with reduced recombination combined with at least one dominant incompatibility locus residing within the X inversion(s). Overall, this study suggests that genetic incompatibilities arising within chromosomal inversions can play an important role in speciation (Poikela, 2022).

    Meiotic Recognition of Evolutionarily Diverged Homologs: Chromosomal Hybrid Sterility Revisited

    Hybrid sterility (HS) is an early postzygotic reproductive isolation mechanism observed in all sexually reproducing species. Infertility of hybrids prevents gene flow between incipient species and leads to speciation. While Drosophila studies have focused almost exclusively on the genic control of HS, two other model species, Mus musculus and budding yeast provided the first experimental evidence of hybrid sterility governed by the nongenic effects of DNA sequence divergence. This study proposes that the nongenic effect of increasing DNA divergence between closely related species may impair mutual recognition of homologous chromosomes and disrupt their synapsis. Unsynapsed or mispaired homologs can induce early meiotic arrest, or their random segregation can cause aneuploidy of spermatids and sperm cells. Impaired recognition of homologs may thus act as a universal chromosomal checkpoint contributing to the complexity of genetic control of HS. Chromosomal HS controlled by the Prdm9 gene in mice and HS driven by the mismatch repair machinery in yeast are currently the most advanced examples of chromosomal homology search-based HS. More focus on the cellular and molecular phenotypes of meiosis will be needed to further validate the role of homolog recognition in hybrid sterility and speciation (Forejt, 2023).

    Comparative genomic analyses provide new insights into the evolutionary dynamics of heterochromatin in Drosophila

    The term heterochromatin has been long considered synonymous with gene silencing, but it is now clear that the presence of transcribed genes embedded in pericentromeric heterochromatin is a conserved feature in the evolution of eukaryotic genomes. Several studies have addressed the epigenetic changes that enable the expression of genes in pericentric heterochromatin, yet little is known about the evolutionary processes through which this has occurred. By combining genome annotation analysis and high-resolution cytology, this study has identified and mapped 53 orthologs of D. melanogaster heterochromatic genes in the genomes of two evolutionarily distant species, D. pseudoobscura and D. virilis. The results show that the orthologs of the D. melanogaster heterochromatic genes are clustered at three main genomic regions in D. virilis and D. pseudoobscura. In D. virilis, the clusters lie in the middle of euchromatin, while those in D. pseudoobscura are located in the proximal portion of the chromosome arms. Some orthologs map to the corresponding Muller C element in D. pseudoobscura and D. virilis, while others localize on the Muller B element, suggesting that chromosomal rearrangements that have been instrumental in the fusion of two separate elements involved the progenitors of genes currently located in D. melanogaster heterochromatin. These results demonstrate an evolutionary repositioning of gene clusters from ancestral locations in euchromatin to the pericentromeric heterochromatin of descendent D. melanogaster chromosomes. Remarkably, in both D. virilis and D. pseudoobscura the gene clusters show a conserved association with the HP1a protein, one of the most highly evolutionarily conserved epigenetic marks. In light of these results, a new scenario is suggested whereby ancestral HP1-like proteins (and possibly other epigenetic marks) may have contributed to the evolutionary repositioning of gene clusters into heterochromatin (Caizzi, 2016).

    Genomics of natural populations: How differentially expressed genes shape the evolution of chromosomal inversions in Drosophila pseudoobscura

    The third chromosome of Drosophila pseudoobscura is a model system to test hypotheses about how rearrangements are established in populations because its third chromosome is polymorphic for > 30 gene arrangements that were generated by a series of overlapping inversion mutations. Circumstantial evidence has suggested that these gene arrangements are selected. Despite the expected homogenizing effects of extensive gene flow, the frequencies of arrangements form gradients or clines in nature, which have been stable since the system was first described more than 80 years ago. Furthermore, multiple arrangements exist at appreciable frequencies across several ecological niches providing the opportunity for heterokaryotypes to form. This study tested whether genes are differentially expressed among chromosome arrangements in first instar larvae, adult females and males. In addition, it was asked whether transcriptional patterns in heterokaryotypes are dominant, semidominant, overdominant, or underdominant. Evidence was found for a significant abundance of differentially expressed genes across the inverted regions of the third chromosome, including an enrichment of genes involved in sensory perception for males. The majority of loci show additivity in heterokaryotypes. These results suggest that multiple genes have expression differences among arrangements that were either captured by the original inversion mutation or accumulated after it reached polymorphic frequencies, providing a potential source of genetic variation for selection to act upon. These data suggest that the inversions are favored because of their indirect effect of recombination suppression that has held different combinations of differentially expressed genes together in the various gene arrangement backgrounds (Fuller, 2016).

    The origin of chromosomal inversions as a source of segmental duplications in the Sophophora subgenus of Drosophila

    Chromosomal inversions can contribute to the adaptation of organisms to their environment by capturing particular advantageous allelic combinations of a set of genes included in the inverted fragment and also by advantageous functional changes due to the inversion process itself that might affect not only the expression of flanking genes but also their dose and structure. Of the two mechanisms originating inversions -ectopic recombination, and staggered double-strand breaks and subsequent repair- only the latter confers the inversion the potential to have dosage effects and/or to generate advantageous chimeric genes. In Drosophila subobscura, there is ample evidence for the adaptive character of its chromosomal polymorphism, with an important contribution of some warm-climate arrangements such as E1+2+9+12. This study has characterized the breakpoints of inversion E12 and established that it originated through the staggered-break mechanism like four of the five inversions of D. subobscura previously studied. This mechanism that also predominates in the D. melanogaster lineage might be prevalent in the Sophophora subgenus and contribute to the adaptive character of the polymorphic and fixed inversions of its species. Finally, the D. subobscura inversion breakpoint regions were shown to have generally been disrupted by additional structural changes that occurred at different time scales (Puerma, 2016).

    Sex-specific evolution of relative leg size in Drosophila prolongata results from changes in the intersegmental coordination of tissue growth

    Evolution of relative organ size is the most prolific source of morphological diversity, yet the underlying molecular mechanisms that modify growth control are largely unknown. Models where organ proportions have undergone recent evolutionary changes hold the greatest promise for understanding this process. Uniquely among Drosophila species, D. prolongata displays a dramatic, male-specific increase in the size of its forelegs relative to other legs. By comparing leg development between males and females of D. prolongata and its closest relative D. carrolli, this study shows that the exaggerated male forelegs are produced by a sex- and segment-specific increase in mitosis during the final larval instar. Intersegmental compensatory control, where smaller leg primordia grow at a faster rate, is observed in both species and sexes. However, the equlibrium growth rates that determine the final relative proportion between the first and second legs have shifted in male D. prolongata compared both to conspecific females and to D. carrolli. It is suggested that the observed developmental changes that produce new adult proportions reflect an interplay between conserved growth coordination mechanisms and evolving organ-specific growth targets (Luecke, 2019).

    Evolution of sexual size dimorphism in the wing musculature of Drosophila

    Male courtship songs in Drosophila are exceedingly diverse across species. While much of this variation is understood to have evolved from changes in the central nervous system, evolutionary transitions in the wing muscles that control the song may have also contributed to song diversity. Focusing on a group of four wing muscles that are known to influence courtship song in Drosophila melanogaster, this study investigated the evolutionary history of wing muscle anatomy of males and females from 19 Drosophila species. Three of the wing muscles have evolved sexual dimorphisms in size multiple independent times, whereas one has remained monomorphic in the phylogeny. These data suggest that evolutionary changes in wing muscle anatomy may have contributed to species variation in sexually dimorphic wing-based behaviors, such as courtship song. Moreover, wing muscles appear to differ in their propensity to evolve size dimorphisms, which may reflect variation in the functional constraints acting upon different wing muscles (Tracy, 2020).

    Resolving between novelty and homology in the rapidly evolving phallus of Drosophila

    The genitalia present some of the most rapidly evolving anatomical structures in the animal kingdom, possessing a variety of parts that can distinguish recently diverged species. In the Drosophila melanogaster group, the phallus is adorned with several processes, pointed outgrowths, that are similar in size and shape between species. However, the complex three-dimensional nature of the phallus can obscure the exact connection points of each process. Previous descriptions based upon adult morphology have primarily assigned phallic processes by their approximate positions in the phallus and have remained largely agnostic regarding their homology relationships. In the absence of clearly identified homology, it can be challenging to model when each structure first evolved. This study employed a comparative developmental analysis of these processes in eight members of the melanogaster species group to precisely identify the tissue from which each process forms. The results indicate that adult phallic processes arise from three pupal primordia in all species. It was found that in some cases the same primordia generate homologous structures whereas in other cases, different primordia produce phenotypically similar but remarkably non-homologous structures. This suggests that the same gene regulatory network may have been redeployed to different primordia to induce phenotypically similar traits. These results highlight how traits diversify and can be redeployed, even at short evolutionary scales (Rice, 2021).

    Evolution and development of male-specific leg brushes in Drosophilidae

    The origin, diversification, and secondary loss of sexually dimorphic characters are common in animal evolution. In some cases, structurally and functionally similar traits have evolved independently in multiple lineages. Prominent examples of such traits include the male-specific grasping structures that develop on the front legs of many dipteran insects. This report describes the evolution and development of one of these structures, the male-specific "sex brush." The sex brush is composed of densely packed, irregularly arranged modified bristles and is found in several distantly related lineages in the family Drosophilidae. Phylogenetic analysis using 250 genes from over 200 species provides modest support for a single origin of the sex brush followed by many secondary losses; however, independent origins of the sex brush cannot be ruled out completely. Sex brushes were shown to develop in very similar ways in all brush-bearing lineages. The dense packing of brush hairs is explained by the specification of bristle precursor cells at a near-maximum density permitted by the lateral inhibition mechanism, as well as by the reduced size of the surrounding epithelial cells. In contrast to the female and the ancestral male condition, where bristles are arranged in stereotypical, precisely spaced rows, cell migration does not contribute appreciably to the formation of the sex brush. The complex phylogenetic history of the sex brush can make it a valuable model for investigating coevolution of sex-specific morphology and mating behavior (Tanaka, 2022).

    Interspecific variation in sex-specific gustatory organs in Drosophila

    Drosophila males use leg gustatory bristles to discriminate between male and female cuticular pheromones as an important part of courtship behavior. In Drosophila melanogaster, several male-specific gustatory bristles are present on the anterior surface of the first tarsal segment of the prothoracic leg, in addition to a larger set of gustatory bristles found in both sexes. These bristles are thought to be specialized for pheromone detection. This study reports the number and location of sex-specific gustatory bristles in 27 other Drosophila species. Although some species have a pattern similar to D. melanogaster, others lack anterior male-specific bristles but have many dorsal male-specific gustatory bristles instead. Some species have both anterior and dorsal male-specific bristles, while others lack sexual dimorphism entirely. In several distantly related species, the number of gustatory bristles is much greater in males than in females due to a male-specific transformation of ancestrally mechanosensory bristles to a chemosensory identity. This variation in the extent and pattern of sexual dimorphism may affect the formation and function of neuronal circuits that control Drosophila courtship and contribute to the evolution of mating behavior (Kopp, 2022).

    Genetic variation of morphological scaling in Drosophila melanogaster

    Morphological scaling relationships between the sizes of individual traits and the body captures the characteristic shape of a species, and their evolution is the primary mechanism of morphological diversification. However, almost no knowledge is available of the genetic variation of scaling, which is critical if how scaling evolves is to be understood. This study explored the genetics of population scaling relationships (scaling relationships fit to multiple genetically-distinct individuals in a population) by describing the distribution of individual scaling relationships (genotype-specific scaling relationships that are unseen or cryptic). These individual scaling relationships harbor the genetic variation in the developmental mechanisms that regulate trait growth relative to body growth, and theoretical studies suggest that their distribution dictates how the population scaling relationship will respond to selection. Using variation in nutrition to generate size variation within 197 isogenic lineages of Drosophila melanogaster, extensive variation was revealed in the slopes of the wing-body and leg-body individual scaling relationships among genotypes. This variation reflects variation in the nutritionally-induced size plasticity of the wing, leg, and body. Surprisingly, it was found that variation in the slope of individual scaling relationships primarily results from variation in nutritionally-induced plasticity of body size, not leg or wing size. These data allow prediction of how different selection regimes affect scaling in Drosophila, and is the first step in identifying the genetic targets of such selection. More generally, this approach provides a framework for understanding the genetic variation of scaling, an important prerequisite to explaining how selection changes scaling and morphology (Wilcox, 2023).

    Homeotic transformations suggest mechanisms for rapid evolution diversification in Drosophila sex combs

    Evolutionary innovations refer to the emergence of new traits, functions, or behaviors in organisms and lineages over time. Although research has demonstrated that such innovations can arise gradually or through small step, the mechanisms by which rapid morphological diversification takes place remain poorly understood. To explore this question, this study used the evolution of sex combs, as a system. This male-specific row of leg bristles, comprising sex combs as a system, because it displays spectacular morphological diversification in a short time. Homeotic mutations in the fruit fly, Drosophila melanogaster, are those which create modifications in one part of a fly to resemble another region. This study described effects of some of these mutations which transform the D. melanogaster fly sex comb morphology to closely resemble sex comb morphology in other species. These findings support previous research indicating that minor alterations to regulatory elements can play a significant role in explaining morphological evolution. Thus, our results suggest that rapid diversification may not require starting from scratch, but rather may require minor modifications to the sex comb ground plan, which may account for its rapid morphological evolution (Doucet, 2023).

    Evolutionary assembly of cooperating cell types in an animal chemical defense system

    How the functions of multicellular organs emerge from the underlying evolution of cell types is poorly understood. This study deconstructed evolution of an organ novelty: a rove beetle gland that secretes a defensive cocktail. This study showed how gland function arose via assembly of two cell types that manufacture distinct compounds. One cell type, comprising a chemical reservoir within the abdomen, produces alkane and ester compounds. This cell type is a hybrid of cuticle cells and ancient pheromone and adipocyte-like cells, executing its function via a mosaic of enzymes from each parental cell type. The second cell type synthesizes benzoquinones using a chimera of conserved cellular energy and cuticle formation pathways. Evolution of each cell type was shaped by coevolution between the two cell types, yielding a potent secretion that confers adaptive value. These findings illustrate how cooperation between cell types arises, generating new, organ-level behaviors (Bruckner, 2021).

    The regulation of a pigmentation gene in the formation of complex color patterns in Drosophila abdomens

    Changes in the control of developmental gene expression patterns have been implicated in the evolution of animal morphology. However, the genetic mechanisms underlying complex morphological traits remain largely unknown. This study investigated the molecular mechanisms that induce the pigmentation gene yellow in a complex color pattern on the abdomen of Drosophila guttifera. At least five developmental genes may collectively activate one cis-regulatory module of yellow in distinct spot rows and a dark shade to assemble the complete abdominal pigment pattern of Drosophila guttifera. One of these genes, wingless, may play a conserved role in the early phase of spot pattern development in several species of the quinaria group. These findings shed light on the evolution of complex animal color patterns through modular changes of gene expression patterns (Raja, 2022).

    Natural variation in Drosophila shows weak pleiotropic effects

    Pleiotropy describes the phenomenon in which a gene affects multiple phenotypes. The extent of pleiotropy is still disputed, mainly because of issues of inadequate power of analyses. A further challenge is that empirical tests of pleiotropy are restricted to a small subset of all possible phenotypes. To overcome these limitations, this paper proposes a new measurement of pleiotropy that integrates across many phenotypes and multiple generations to improve power. Pleiotropy is infered from the fitness cost imposed by frequency changes of pleiotropic loci. Mixing Drosophila simulans populations, which adapted independently to the same new environment using different sets of genes, this study shows that the adaptive frequency changes have been accompanied by measurable fitness costs. Unlike previous studies characterizing the molecular basis of pleiotropy, this study shows that many loci, each of weak effect, contribute to genome-wide pleiotropy. It is proposed that the costs of pleiotropy are reduced by the modular architecture of gene expression, which facilitates adaptive gene expression changes with low impact on other functions (Christodoulaki, 2022).

    Life history evolution and cellular mechanisms associated with increased size in high-altitude Drosophila

    Understanding the physiological and genetic basis of growth and body size variation has wide-ranging implications, from cancer and metabolic disease to the genetics of complex traits. This study examined the evolution of body and wing size in high-altitude Drosophila melanogaster from Ethiopia, flies with larger size than any previously known population. Specifically, attempts were made to identify life history characteristics and cellular mechanisms that may have facilitated size evolution. The large-bodied Ethiopian flies laid significantly fewer but larger eggs relative to lowland, smaller-bodied Zambian flies. The highland flies were found to achieve larger size in a similar developmental period, potentially aided by a reproductive strategy favoring greater provisioning of fewer offspring. At the cellular level, cell proliferation was a strong contributor to wing size evolution, but both thorax and wing size increases involved important changes in cell size. Nuclear size measurements were consistent with elevated somatic ploidy as an important mechanism of body size evolution. The significance of these results for the genetic basis of evolutionary changes in body and wing size in Ethiopian D. melanogaster is discussed (Lack, 2016).

    Profiling cellular diversity in sponges informs animal cell type and nervous system evolution

    The evolutionary origin of metazoan cell types such as neurons and muscles is not known. Using whole-body single-cell RNA sequencing in a sponge, an animal without nervous system and musculature, 18 distinct cell types were identified. These include nitric oxide-sensitive contractile pinacocytes, amoeboid phagocytes, and secretory neuroid cells that reside in close contact with digestive choanocytes that express scaffolding and receptor proteins. Visualizing neuroid cells by correlative x-ray and electron microscopy revealed secretory vesicles and cellular projections enwrapping choanocyte microvilli and cilia. These data show a communication system that is organized around sponge digestive chambers, using conserved modules that became incorporated into the pre- and postsynapse in the nervous systems of other animals (Musser, 2021).

    Sponges represent a basal animal clade that lack neurons, muscles, and gut. They display canals for filter-feeding and waste removal and are composed of three tissues: pinacocytes lining the canals, outer covering, and basal attachment layer; chambers of choanocytes with microvilli for food capture and motile cilia that drive water flow, and an inner mesohyl composed of stem, skeletogenic, and other mesenchymal cells. Despite their simple organization, sponges have genes that are usually expressed in neurons or muscles, including components of the pre- and postsynapse, and perform whole-body contractions that flush the canal system and expel debris. However, cells with integrative signaling functions are yet unknown (Musser, 2021).

    Using whole-body single-cell RNA sequencing, a comprehensive survey was conducted of genetically distinguishable cell types in 8-day-old freshwater demosponge Spongilla lacustris. Four capture experiments provided 10,106 S. lacustris cells expressing 26,157 genes (Musser, 2021).

    Louvain graph clustering resolved 42 cell clusters with distinct expression signatures. Projection into two-dimensional expression space revealed a central cluster from which other clusters emanated. This cluster expressed Noggin, Musashi1, and Piwi-like, demarcating stem cell-like archaeocytes. Developmental relationships were explored using partition-based graph abstraction (PAGA), which assesses the degree of connectivity among clusters. This revealed connections along each arm of the t-distributed stochastic neighbor embedding (tSNE) plot and with many isolated clusters, suggesting developmental trajectories from archaeocytes to all other clusters. Supporting this, archaeocyte marker expression decreased with distance from the central cluster. Interconnecting clusters exhibited profiles intermediate between archaeocytes and peripheral clusters, with few specific markers. By contrast, peripheral clusters showed distinctive expression profiles of transcription factors and effector genes, which indicates differentiated cell types (Musser, 2021).

    Cell clusters were imaged via single-molecule fluorescent in situ hybridization (smFISH) of selected marker genes. This resolved spatial relationships of stem cells, developmental progenitors, and differentiated cell types. Probes for the archaeocyte marker Eef1a1 labeled large mesenchymal cells with a prominent nucleolus. Peripheral clusters 10 and 11 identified as choanocytes and apopylar cells by expression of actin-binding Villin and other choanocyte markers, whereas intermediate clusters 8 and 9 expressed proliferation markers, including Pcna, representing choanoblasts that often neighbored choanocyte chambers. Following similar strategies, 18 differentiated cell types were assigned that represented a comprehensive molecular classification of Spongilla cell types consistent with previous morphological classification. For 13 previously described cell types, traditional nomenclature or Greek translations were used. Five mesenchymal cell types were previously unrecognized, described in this study as myopeptidocytes, metabolocytes, and three different mesocytes (Musser, 2021).

    Animal cell types are organized into families, which share expression of regulatory and effector genes and are identified by phylogenetic analysis. First weighted correlation network analysis was used to identify gene sets that covary across differentiated cell types. This revealed 28 distinct gene sets, delineating individual cell types and cell type groups, which hinted at the presence of hierarchical organization. This was validated via a 'treeness' score that was estimated for every combination of four cell types (tetrads), with close to 60% of tetrads exhibiting greater hierarchy than expected by chance. This indicated strong support for gene expression hierarchy that is independent of gene set or normalization method (Musser, 2021).

    Then, a cell type tree was generated using neighbor-joining tree reconstruction, which revealed well-supported clades of differentiated cell types robust to bootstrapping and variable gene sets. Major cell type clades included extended pinacocyte and choanocyte families, as well as two families of mesenchymal cells, one of which contained amoebocytes and neuroid cells and another of which contained sclerocytes and mesocytes that are enriched for noncoding genes. Notably, mesenchymal cell types were observed scattered across all families and internested with epithelial cell types. Evolutionary quantitative trait modeling revealed clade-specific genes and expression changes across the cell type tree (Musser, 2021).

    Assessing evolutionary conservation of cell types across sponges, self-assembling manifold mapping (SAMap) was used to align Spongilla cells to a smaller single-cell dataset that was collected from adults of the demosponge Amphimedon queenslandica, which had a coarse identification of cell types based on expression signatures. Consistent alignment of cell types within each family were found, albeit with higher resolution of annotated Spongilla pinacocyte- and choanocyte-related cell types. Newly identified Spongilla cell types aligned broadly with Amphimedon pinacocytes, as with metabolocytes, or were called an intermediate 'choano-to-pinaco' cluster in Amphimedon, as with myopeptidocytes. For several Spongilla cell types, there were no Amphimedon counterparts, possibly because of incomplete cell type assignments in this dataset (Musser, 2021).

    Each major cell type family was named to reflect its role within the organism. The family of endymocytes (νδνμα: 'lining, clothing') covers and shapes the sponge body. Incurrent pinacocytes constitute both layers of the tent, the vestibule lining, and the outer osculum layer. Apendopinacocytes line the excurrent canals and inner osculum layer. Basopinacocytes make up the basal epithelial layer attached to the substrate. Mesenchymal endymocytes were often found in proximity to pinacocytes and include collagen-secreting lophocytes, sclerophorocytes, and metabolocytes. Gene ontology (GO) analysis for endymocyte-specific markers found strong enrichment for Wnt and transforming growth factor-β (TGF-β) signaling and actomyosin-based contractility, which is consistent with pinacocytes mediating whole-body contractions. Endymocytes also express contractile-cell master regulators serum response factor (Srf) and Csrp1/2/3 (also known as muscle LIM protein), which suggests a conserved regulatory module for actomyosin contractility (Musser, 2021).

    In other demosponges, the signaling molecules γ-aminobutyric acid (GABA), glutamate, and nitric oxide (NO) alter whole-body contractions. Paralogs of the metabotropic GABAB receptor used in distinct endymocytes were found. Pinacocytes also coexpressed nitric oxide synthase, which catalyzes synthesis of NO, together with the NO receptor Gucy1B2. In the marine demosponge Tethya wilhelma, NO induces and modulates whole-body contractions but only affected the osculum in the freshwater sponge Ephydatia muelleri. During the S. lacustris contraction cycle, the collapse of osculum and incurrent systems first causes excurrent canals to swell, which subsequently shrink to expel water through the osculum before returning to the resting state. The responses to NO were tested by treating juvenile sponges with NOC-12, a donor of NO, and 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of the NO receptor. NO release immediately shrank the incurrent system, including incurrent canals and tent, and expanded the excurrent canals, as during initial stages of the contraction cycle. Subsequently, the incurrent system exhibited short, pulsed movements and returned to resting state only after NO removal. The subtler effect of ODQ treatment involved expansion of incurrent, and possibly excurrent, canal systems. Serial combinations of NOC-12 and ODQ gave similar results, establishing a key role of NO in initiating and regulating the contraction cycle in S. lacustris, and possibly ancestrally in demosponges (Musser, 2021).

    Beyond contraction, cell type-specific expression programs indicated endymocyte roles in photo- and mechanosensation, skeleton formation, glucose metabolism, and production of reactive oxygen for defense. Single orthologs of Six and Pax are expressed in a complementary manner, with Six+ incurrent pinacocytes enriched for genes involved in circadian clock entrainment, and the blue-light sensor cryptochrome, which suggests light sensitivity, and PaxB+ apendopinacocytes expressing mechanosensory components and exhibiting short cilia. Next, basopinacocytes were found enwrapping spicules anchored at the base of the sponge and sclerophorocytes were found forming clusters alongside mature spicules, similar to SoxB+ spicule 'transport cells' in E. muelleri. Both are enriched in genes that organize fibrillar collagen, and sclerophorocytes in secretory pathway genes. Multipolar metabolocytes exhibit wide extensions that may contact pinacocytes. They exhibit manifold metabolic activity, with specific up-regulation of the complete set of enzymes that mediate glycolysis and the pentose phosphate pathway, and specific expression of glycogen phosphorylase and pyruvate dehydrogenase. Metabolocytes also express the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex known to produce reactive oxygen species for bacterial defense (Musser, 2021).

    The family of peptidocytes (πξπτξιν, 'to digest') share a role in digestion that is reflected by phagocytic vesicle and lytic vacuole gene expression. This family is comprised of choanocytes and apopylar cells that form the excurrent pore of choanocyte chambers. Myopeptidocytes are an abundant constituent of the mesohyl with long projections that contact each other and other cells, including choanocytes. They express actomyosin-based contractility modules and three orthologs of Mib2 that regulates myofiber integrity, indicating a possible role for mesohyl in contractions (Musser, 2021).

    In line with digestion functions, choanocytes express the transcription factors Rbpj, Klf5, and NK homeobox 6, and sorting nexin family members involved in macropinocytosis, an unregulated form of engulfment. The choanocyte subclade is enriched for genes of the receptive/postsynapse complex in animals with neurons, including 'postsynaptic scaffold' (homer, shank, and Baiap2) and 'dystrophin-syntrophin signaling complex'. Notably, scaffold genes such as Baiap2 and Eps8 are also active in organizing the actin skeleton of microvilli, and the single ortholog of ezrin, radixin, and moesin, known to stabilize the microvillar cytoskeleton, colocalized with F-actin in choanocyte microvilli. These data suggest a role of postsynapse-like scaffolding machinery in the choanocyte microvillar.

    The amoeboid-neuroid family comprises three small, tri- or multiangular cell types. The neuroid cells, also called 'central cells', associate with choanocyte chambers, whereas amoebocytes and granulocytes are dispersed in the mesohyl. Granulocytes are next to tent pinacocytes. Amoebocytes bear long extensions and were seen to engulf other mesohyl cells, consistent with a macrophage-like role and classification as 'bactericidal' cells in A. queenslandica. Family-specific transcription factors suggest a role in innate immunity. Nuclear factor kappa B subunit (NFκB), which controls cellular immune responses, and high mobility group box 1/2/3 (Hmgb1/2/3) are universal sentinels of the nucleic acid-mediated innate immune response and activate key inflammatory pathways. Furthermore, amoebocytes specifically express the only Nfat ortholog, active in adaptive and innate immunity, and Gata, a conserved determinant of immunocytes. It was also noted family-specific expression of engulfment and cell motility (Elmo), which is essential for engulfing dying cells in worms, and the small guanosine triphosphatase Rab21, which is fundamental for phagosome formation (Musser, 2021).

    Neuroid cells exhibited a secretory profile via up-regulation of the signal peptidase complex and enrichment for 'presynaptic' gene sets (also observed in endymocytes, suggesting communication via vesicle secretion. Notably, nearly all neuroid cells were associated with choanocyte chambers, with most chambers containing at least one neuroid cell in the middle of the chamber or in its lining (Musser, 2021).

    To further characterize neuroid cell interactions, a two-step imaging strategy was devised, correlating confocal light microscopy and laboratory- or synchrotron-based x-ray imaging with focused ion beam scanning electron microscopy (FIB-SEM). These volumes are publicly accessible via the interactive FIJI plugin MoBIE. First, a lower-resolution FIB-SEM volume was acquired of an entire choanocyte chamber that contained two neuroid cells, identified by light microscopy. Using machine learning, the entire volume was segmented and one neuroid cell was found positioned centrally and another near the apopylar pore, each with multiple protrusions directed toward different choanocyte collars and nearly always contacting and enwrapping one or more microvilli. Occasionally, extensions followed cilia that emerged straight and then bent, in contrast to normal undulatory cilia, which suggested that they may pause beating (Musser, 2021).

    Second, subcellular details were captured of two additional neuroid cells via high-resolution FIB-SEM. Exploiting the deep penetration of x-rays, the large field of view that was acquired via a laboratory-based x-ray microCT (microscopic x-ray computed tomography) was combined with the smaller, higher-resolution field of view recordable on a synchrotron beamline. Registration of the synchrotron tomogram to the full sample block enabled precise trimming and acquisition of higher-resolution FIB-SEM data. This method is termed correlative x-ray electron microscopy (CXEM). In these volumes, numerous secretory vesicles 50 to 500 nm in size were observed throughout both neuroid cells, including in the cellular protrusions, and two Golgi stacks per cell, each oriented toward the cellular protrusions. Larger vacuoles represented endolysosomes or phagosomes and contained heterogeneous material, including a likely bacterial cell, consistent with phagocytosis and engulfment gene expression. Lastly, both neuroid cells formed long invaginating pockets that encased cilia tips with shaft-like constrictions. Direct contact was never observed between neuroid cells and choanocyte collar or cilia that would have resembled synapses with targeted vesicle release. Together, these observations suggest a dual role for neuroid cells in intercellular communication and in the clearing of bacteria or cellular debris within choanocyte chambers (Musser, 2021).

    This study observed significant hierarchical organization among differentiated cell type expression programs in Spongilla, as reflected by transcription factors and functional modules that are shared across subclades in the cell type tree. It is proposed that this reflects evolutionary relatedness rather than homoplasy and that major sponge cell type families, such as endymocytes and peptidocytes, originated via cell type diversification. These evolutionary lineages are distinct from developmental trajectories, although both histories can be congruent when closely related transcriptional programs arise from the same developmental precursors, as observed in this work (Musser, 2021).

    For endymocytes, the experiments revealed coordination of the contraction cycle via NO signaling, which also triggers endothelial muscle relaxation in vertebrates. Endymocyte transcription factor signatures support an evolutionary link between sensory-contractile systems in sponges and other animals. In Spongilla and the calcisponge Sycon ciliatum, pinacocytes specifically express the sole sponge ortholog of Msx, which is known to specify sensory ectodermal regions and myocytes in other animals. Msx activates atonal, which plays a conserved role in mechanosensory neuron specification and demarcates sponge pinacocytes together with its binding partner Tcf4/E12/47. Most notably, apendopinacocytes and incurrent pinacocytes express the single sponge orthologs of the Pax and Six homeodomain transcription factors, respectively, that also play conserved roles in sensory cell and myocyte specification. The data are consistent with the hypothesis that sensory cells and myocytes arose by division of labor from shared evolutionary precursors that formed sensory-contractile, conducting epithelia in metazoan ancestors (Musser, 2021).

    For peptidocytes, analysis of cellular transcriptomes suggests digestive functions. Peptidocytes specifically express Klf5, which controls cytodifferentiation of intestinal epithelia, and choanocytes express Nkx6, Rbpj, and Notch that specify pancreatic cell types and absorptive enterocytes. Nkx6 also demarcates pharyngeal and exocrine gland cells in sea anemone. Peptidocytes thus may have existed in metazoan ancestors, initially with intracellular digestion as observed in sponges and their unicellular relatives and then acquiring external digestion, first as part of a digestive mucociliary sole and then incorporated into the gut (Musser, 2021).

    For neuroid cells, the data suggest communicative functions within choanocyte chambers. Their close physical interaction with choanocyte microvillar collars and cilia, the expression of secretory genes, and the presence of secretory vesicles suggest a coordinative role in feeding, possibly by modulating ciliary arrest. Spongilla is a sponge with open architecture, in which incoming particles are continuously removed to prevent clogging. For this, the neuroid cells may stop water flow, engulf intruding cells and/or debris, and regulate microbial food uptake in response to quality and availability. Homology of neuroid cells to other animal cell types is unclear, as their transcription factor identity suggests no clear affinity other than limited resemblance to innate immune cells. All three cell type families use conserved neural gene sets. This parallels the wider occurrence of neural modules across epithelial and fiber cells in the simple placozoans and showcases possible parallel routes toward neuron evolution. In line with this, the contractile network and neurosecretory network hypotheses envisage the origin of neurons in distinct cellular contexts that resemble endymocytes and peptidocytes. This work thus puts sponges center stage in elucidating nervous system evolution (Musser, 2021).

    Identification of Evolutionarily Conserved Nuclear Matrix Proteins and Their Prokaryotic Origins

    Compared to prokaryotic cells, a typical eukaryotic cell is much more complex along with its endomembrane system and membrane-bound organelles. Although the endosymbiosis theories convincingly explain the evolution of membrane-bound organelles such as mitochondria and chloroplasts, very little is understood about the evolutionary origins of the nucleus, the defining feature of eukaryotes. Most studies on nuclear evolution have not been able to take into consideration the underlying structural framework of the nucleus, attributed to the nuclear matrix (NuMat), a ribonucleoproteinaceous structure. This can largely be attributed to the lack of annotation of its core components. Since NuMat has been shown to provide a structural platform for facilitating a variety of nuclear functions such as replication, transcription, and splicing, it is important to identify its protein components to better understand these processes. In this study, this issue was addressed using the developing embryos of Drosophila melanogaster and Danio rerio; 362 core NuMat proteins were identified that are conserved between the two organisms. These results were compared with publicly available Mus musculus NuMat dataset and Homo sapiens cellular localization dataset to define the core homologous NuMat proteins consisting of 252 proteins. Of them, 86 protein groups have originated from pre-existing proteins in prokaryotes. While 36 were conserved across all eukaryotic supergroups, 14 new proteins evolved before the evolution of the last eukaryotic common ancestor and together, these 50 proteins out of the 252 core conserved NuMat proteins are conserved across all eukaryotes, indicating their indispensable nature for nuclear function for over 1.5 billion years of eukaryotic history. This analysis paves the way to understand the evolution of the complex internal nuclear architecture and its functions (Sureka, 2021).

    Structural basis of diversity and homodimerization specificity of zinc-finger-associated domains in Drosophila

    In arthropods, zinc finger-associated domains (ZADs) are found at the N-termini of many DNA-binding proteins with tandem arrays of Cys2-His2 zinc fingers (ZAD-C2H2 proteins). ZAD-C2H2 proteins undergo fast evolutionary lineage-specific expansion and functional diversification. This study shows that all ZADs from Drosophila melanogaster form homodimers, but only certain ZADs with high homology can also heterodimerize. CG2712, for example, is unable to heterodimerize with its paralog, the previously characterized insulator protein Zw5, with which it shares 46% homology. A crystal structure was obtained of CG2712 protein's ZAD domain that, in spite of a low sequence homology, has similar spatial organization with the only known ZAD structure (from Grauzone protein). Steric clashes prevented the formation of heterodimers between Grauzone and CG2712 ZADs. Using detailed structural analysis, site-directed mutagenesis, and molecular dynamics simulations, this study demonstrated that rapid evolutionary acquisition of interaction specificity was mediated by the more energy-favorable formation of homodimers in comparison to heterodimers, and that this specificity was achieved by multiple amino acid substitutions resulting in the formation or breaking of stabilizing interactions. It is speculated that specific homodimerization of ZAD-C2H2 proteins is important for their architectural role in genome organization (Bonchuk, 2021).

    Accelerated pseudogenization on the neo-X chromosome in Drosophila miranda

    Y chromosomes often degenerate via the accumulation of pseudogenes and transposable elements. By contrast, little is known about X-chromosome degeneration. This study compared the pseudogenization process between genes on the neo-sex chromosomes in Drosophila miranda and their autosomal orthologues in closely related species. The pseudogenization rate on the neo-X is much lower than the rate on the neo-Y, but appears to be higher than the rate on the orthologous autosome in D. pseudoobscura. Genes under less functional constraint and/or genes with male-biased expression tend to become pseudogenes on the neo-X, indicating the accumulation of slightly deleterious mutations and the feminization of the neo-X. A weak trend was found that the genes with female-benefit/male-detriment effects identified in D. melanogaster are pseudogenized on the neo-X, implying the masculinization of the neo-X. These observations suggest that both X and Y chromosomes can degenerate due to a complex suite of evolutionary forces (Nozawa, 2016).

    The landscape of A-to-I RNA editome is shaped by both positive and purifying selection

    The hydrolytic deamination of adenosine to inosine (A-to-I editing) in precursor mRNA induces variable gene products at the post-transcription level. How and to what extent A-to-I RNA editing diversifies transcriptome is not fully characterized in the evolution, and very little is known about the selective constraints that drive the evolution of RNA editing events. This study on A-to-I RNA editing, by generating a global profile of A-to-I editing for a phylogeny of seven Drosophila species, presents a model system spanning an evolutionary timeframe of approximately 45 million years. Of totally 9281 editing events identified, 5150 (55.5%) are located in the coding sequences (CDS) of 2734 genes. Phylogenetic analysis places these genes into 1,526 homologous families, about 5% of total gene families in the fly lineages. Based on conservation of the editing sites, the editing events in CDS are categorized into three distinct types, representing events on singleton genes (type I), and events not conserved (type II) or conserved (type III) within multi-gene families. While both type I and II events are subject to purifying selection, notably type III events are positively selected, and highly enriched in the components and functions of the nervous system. The tissue profiles are documented for three editing types, and their critical roles are further implicated by their shifting patterns during holometabolous development and in post-mating response. In conclusion, three A-to-I RNA editing types are found to have distinct evolutionary dynamics. It appears that nervous system functions are mainly tested to determine if an A-to-I editing is beneficial for an organism. The coding plasticity enabled by A-to-I editing creates a new class of binary variations, which is a superior alternative to maintain heterozygosity of expressed genes in a diploid mating system (Yu, 2016).

    Weak polygenic selection drives the rapid adaptation of the chemosensory system: lessons from the upstream regions of the major gene families

    The animal chemosensory system is involved in essential biological processes, most of them mediated by proteins encoded in multigene families. These multigene families have been fundamental for the adaptation to new environments, significantly contributing to phenotypic variation. This adaptive potential contrasts, however, with the lack of studies at their upstream regions, especially taking into account the evidence linking their transcriptional changes to certain phenotypic effects. This study explicitly characterised the contribution of the upstream sequences of the major chemosensory gene families to rapid adaptive processes. For that, the genome sequences of 158 lines were analyzed from a population of Drosophila melanogaster that recently colonised North America, and functional and transcriptional data available for this species were integrated. Both, strong negative and strong positive selection were found to shape transcriptional evolution at the genome-wide level. The chemosensory upstream regions, however, exhibit a distinctive adaptive landscape, including multiple mutations of small beneficial effect and a reduced number of cis-regulatory elements. Together, these results suggest that the promiscuous and partially redundant transcription and function of the chemosensory genes provide evolutionarily opportunities for rapid adaptive episodes through weak polygenic selection (Librado, 2016).

    Evolutionary dynamics of abundant stop codon readthrough

    This study leveraged comparative genomic evidence across 21 Anopheles mosquitoes to systematically annotate translational stop codon readthrough genes in the malaria vector Anopheles gambiae, and to provide the first study of abundant readthrough evolution, by comparison with 20 Drosophila species. Evolutionary signatures were identified of conserved, functional readthrough of 353 stop codons in the malaria vector, Anopheles gambiae, and of 51 additional Drosophila melanogaster stop codons. Most differences between the readthrough repertoires of the two species arose from readthrough gain or loss in existing genes, rather than birth of new genes or gene death; that readthrough-associated RNA structures are sometimes gained or lost while readthrough persists; that readthrough is more likely to be lost at TAA and TAG stop codons; and that readthrough is under continued purifying evolutionary selection in mosquito, based on population genetic evidence. Readthrough-associated gene properties were determined that predate readthrough, and differences were identified in the characteristic properties of readthrough genes between clades. More than 600 functional readthrough stop codons were identified in mosquito and 900 in fruit fly, provide evidence of readthrough control of peroxisomal targeting, and the phylogenetic extent of abundant readthrough as following divergence from centipede was refined (Jungreis, 2016).

    Molecular population genetics of the Polycomb genes in Drosophila subobscura
    Polycomb group (PcG) proteins are important regulatory factors that modulate the chromatin state. They form protein complexes that repress gene expression by the introduction of posttranslational histone modifications. The study of PcG proteins divergence in Drosophila revealed signals of coevolution among them and an acceleration of the nonsynonymous evolutionary rate in the lineage ancestral to the obscura group species, mainly in subunits of the Pcl-PRC2 complex. This study examined the nucleotide polymorphism of PcG genes in a natural population of D. subobscura to detect whether natural selection has also modulated the evolution of these important regulatory genes in a more recent time scale. Results show that most genes are under the action of purifying selection and present a level and pattern of polymorphism consistent with predictions of the neutral model, the exceptions being Su(z)12 and Pho. MK tests indicate an accumulation of adaptive changes in the SU(Z)12 protein during the divergence of D. subobscura and D. guanche. In contrast, the HKA test shows a deficit of polymorphism at Pho. The most likely explanation for this reduced variation is the location of this gene in the dot-like chromosome and would indicate that this chromosome also has null or very low recombination in D. subobscura, as reported in D. melanogaster (Calvo-Martin, 2017).

    Translating natural genetic variation to gene expression in a computational model of the Drosophila gap gene regulatory network
    This study applied a sequence-level model of gap gene expression in the early development of Drosophila to analyze single nucleotide polymorphisms (SNPs) in a panel of natural sequenced D. melanogaster lines. Using a thermodynamic modeling framework, both analytical and computational descriptions are provided of how single-nucleotide variants affect gene expression. The analysis reveals that the sequence variants increase (decrease) gene expression if located within binding sites of repressors (activators). The sign of SNP influence (activation or repression) may change in time and space. The thermodynamic modeling approach predicts non-local and non-linear effects arising from SNPs, and combinations of SNPs, in individual fly genotypes. Simulation of individual fly genotypes using this model reveals that this non-linearity reduces to almost additive inputs from multiple SNPs. Further, signatures are seen of the action of purifying selection in the gap gene regulatory regions. To infer the specific targets of purifying selection, the patterns of polymorphism in the data were analyzed at two phenotypic levels: the strengths of binding and expression. Combinations of SNPs show evidence of being under selective pressure, while individual SNPs do not. The model predicts that SNPs appear to accumulate in the genotypes of the natural population in a way biased towards small increases in activating action on the expression pattern (Gursky, 2017).

    Negative frequency dependent selection contributes to the maintenance of a global polymorphism in mitochondrial DNA

    Understanding the forces that maintain diversity across a range of scales is at the very heart of biology. Frequency-dependent processes are generally recognized as the most central process for the maintenance of ecological diversity. The same is, however, not generally true for genetic diversity. Negative frequency dependent selection, where rare genotypes have an advantage, is often regarded as a relatively weak force in maintaining genetic variation in life history traits because recombination disassociates alleles across many genes. Yet, many regions of the genome show low rates of recombination and genetic variation in such regions (i.e., supergenes) may in theory be upheld by frequency dependent selection. This group studied what is essentially a ubiquitous life history supergene (i.e., mitochondrial DNA) in the fruit fly Drosophila subobscura, showing sympatric polymorphism with two main mtDNA genotypes co-occurring in populations world-wide. Using an experimental evolution approach involving manipulations of genotype starting frequencies, this study shows that negative frequency dependent selection indeed acts to maintain genetic variation in this region. Moreover, the strength of selection was affected by food resource conditions. This work provides novel experimental support for the view that balancing selection through negative frequency dependency acts to maintain genetic variation in life history genes. It is suggested that the emergence of negative frequency dependent selection on mtDNA is symptomatic of the fundamental link between ecological processes related to resource use and the maintenance of genetic variation (Kurbalija Novicic, 2020).

    Towards an Evolutionarily Appropriate Null Model: Jointly Inferring Demography and Purifying Selection

    The question of the relative evolutionary roles of adaptive and non-adaptive processes has been a central debate in population genetics for nearly a century. While advances have been made in the theoretical development of the underlying models, and statistical methods for estimating their parameters from large-scale genomic data, a framework for an appropriate null model remains elusive. A model incorporating evolutionary processes known known to be in constant operation - genetic drift (as modulated by the demographic history of the population) and purifying selection - is lacking. Without such a null model, the role of adaptive processes in shaping within- and between-population variation may not be accurately assessed. This study investigated how population size changes and the strength of purifying selection affect patterns of variation at neutral sites near functional genomic components. A novel statistical framework is proposed for jointly inferring the contribution of the relevant selective and demographic parameters. By means of extensive performance analyses, the utility of the approach was quantified, the most important statistics for parameter estimation were identified, and the results with existing methods were compared. Finally, genome-wide population-level data was re-analyzed from a Zambian population of Drosophila melanogaster, and it was found that the population has experienced a much slower rate of population growth than was inferred when the effects of purifying selection were neglected. This approach represents an appropriate null model, against which the effects of positive selection can be assessed (Johri, 2020).

    Molecular evolution and the decline of purifying selection with age

    Life history theory predicts that the intensity of selection declines with age, and this trend should impact how genes expressed at different ages evolve. This study finds consistent relationships between a gene's age of expression and patterns of molecular evolution in two mammals (the human Homo sapiens and the mouse Mus musculus) and two insects (the malaria mosquito Anopheles gambiae and the fruit fly Drosophila melanogaster). When expressed later in life, genes fix nonsynonymous mutations more frequently, are more polymorphic for nonsynonymous mutations, and have shorter evolutionary lifespans, relative to those expressed early. The latter pattern is explained by a simple evolutionary model. Further, early-expressed genes tend to be enriched in similar gene ontology terms across species, while late-expressed genes show no such consistency. In humans, late-expressed genes are more likely to be linked to cancer and to segregate for dominant disease-causing mutations. Last, the effective strength of selection (N(e) s) decreases and the fraction of beneficial mutations increases with a gene's age of expression. These results are consistent with the diminishing efficacy of purifying selection with age, as proposed by Medawar's classic hypothesis for the evolution of senescence, and provide links between life history theory and molecular evolution (Cheng, 2021).

    Sex differences in deleterious mutational effects in Drosophila melanogaster: combining quantitative and population genetic insights

    Fitness effects of deleterious mutations can differ between females and males due to (1) sex differences in the strength of purifying selection, and (2) sex differences in ploidy. Although sex differences in fitness effects have important broader implications (e.g., for the evolution of sex and lifespan), few studies have quantified their scope. Those that have belong to one of two distinct empirical traditions: (1) quantitative genetics, which focusses on multi-locus genetic variances in each sex, but is largely agnostic about their genetic basis, and (2) molecular population genetics, which focusses on comparing autosomal and X-linked polymorphism, but is poorly suited for inferring contemporary sex differences. This study combined both traditions to present a comprehensive analysis of female and male adult reproductive fitness among 202 outbred, laboratory-adapted, hemiclonal genomes of Drosophila melanogaster. While no clear evidence was found for sex differences in the strength of purifying selection, sex differences in ploidy generate multiple signals of enhanced purifying selection for X-linked loci. These signals are present in quantitative genetic metrics: i.e., a disproportionate contribution of the X to male (but not female) fitness variation and population genetic metrics (i.e., steeper regressions of an allele's average fitness effect on its frequency, and proportionally less nonsynonymous polymorphism on the X than autosomes). Fitting these data to models for both sets of metrics, it was inferred that deleterious alleles are partially recessive. Given the often large gap between quantitative and population genetic estimates of evolutionary parameters, this study showcases the benefits of combining genomic and fitness data when estimating such parameters (Ruzicka, 2021).

    The genomic distribution of transposable elements is driven by spatially variable purifying selection
    It is widely accepted that the genomic distribution of transposable elements (TEs) mainly reflects the outcome of purifying selection and insertion bias (1). Nevertheless, the relative importance of these two evolutionary forces could not be tested thoroughly. This study introduced an experimental system, which allows separating purifying selection from TE insertion bias. Experimental evolution was used to study the TE insertion patterns in Drosophila simulans founder populations harboring 1040 insertions of an active P-element. After 10 generations at a large population size, strong selection was detected against P-element insertions. The exception were P-element insertions in genomic regions for which a strong insertion bias has been proposed. Because recurrent P-element insertions cannot explain this pattern, it is concluded that purifying selection, with variable strength along the chromosomes, is the major determinant of the genomic distribution of P-elements. Genomic regions with relaxed purifying selection against P-element insertions exhibit normal levels of purifying selection against base substitutions. This suggests that different types of purifying selection operate on base substitutions and P-element insertions. These results highlight the power of experimental evolution to understand basic evolutionary processes, which are difficult to infer from patterns of natural variation alone (Langmuller, 2023).

    Long-term evolution of quantitative traits in the Drosophila melanogaster species subgroup

    Quantitative genetics aims at untangling the genetic and environmental effects on phenotypic variation. Trait heritability, which summarizes the relative importance of genetic effects, is estimated at the intraspecific level, but theory predicts that heritability could influence long-term evolution of quantitative traits. The phylogenetic signal concept bears resemblance to heritability and it has often been called species-level heritability. Under certain conditions, such as trait neutrality or contribution to phylogenesis, within-species heritability and between-species phylogenetic signal should be correlated. This study investigated the potential relationship between these two concepts by examining the evolution of multiple morphological traits for which heritability has been estimated in Drosophila melanogaster. Specifically, 42 morphological traits in both sexes on a phylogeny were analysed, inferred from 22 nuclear genes for nine species of the melanogaster subgroup. Pagel's λ was used as a measurement of phylogenetic signal because it is the least influenced by the number of analysed taxa. Pigmentation traits showed the strongest concordance with the phylogeny, but no correlation was found between phylogenetic signal and heritability estimates mined from the literature. Data was obtained for multiple climatic variables inferred from the geographical distribution of each species. Phylogenetic regression of quantitative traits on climatic variables showed a significantly positive correlation with heritability. Convergent selection, the response to which depends on the trait heritability, may have led to the null association between phylogenetic signal and heritability for morphological traits in Drosophila. The possible causes of discrepancy between both statistics was discussed and caution against their confusion in evolutionary biology (Yassin, 2022).

    Maintenance of quantitative genetic variance in complex, multi-trait phenotypes: The contribution of rare, large effect variants in two Drosophila species

    The interaction of evolutionary processes to determine quantitative genetic variation has implications for contemporary and future phenotypic evolution, as well as for the ability to detect causal genetic variants. While theoretical studies have provided robust predictions to discriminate among competing models, empirical assessment of these has been limited. In particular, theory highlights the importance of pleiotropy in resolving observations of selection and mutation, but empirical investigations have typically been limited to few traits. This study applied high dimensional Bayesian Sparse Factor Genetic modelling to gene expression datasets in two species, Drosophila melanogaster and D. serrata, to explore the distributions of genetic variance across high-dimensional phenotypic space. Surprisingly, most of the heritable trait covariation was due to few lines (genotypes) with extreme (>3 interquartile ranges from the median) values. Intriguingly, while genotypes extreme for a multivariate factor also tended to have a higher proportion of individual traits that were extreme, genotypes were also observed that were extreme for multivariate factors but not for any individual trait. Other consistent differences between heritable multivariate factors with outlier lines vs. those factors without extreme values, including differences in gene functions. These observations were used to identify further data required to advance understanding of the evolutionary dynamics and nature of standing genetic variation for quantitative traits (Hine, 2022).

    Origins and evolution of human tandem duplicated exon substitution events

    The mutually exclusive splicing of tandem duplicated exons produces protein isoforms that are identical save for a homologous region that allows for the fine tuning of protein function. Tandem duplicated exon substitution events are rare, yet highly important alternative splicing events. Most events are ancient, their isoforms are highly expressed, and they have significantly more pathogenic mutations than other splice event. This study analysed the physicochemical properties and functional roles of the homologous polypeptide regions produced by the 236 tandem duplicated exon substitutions annotated in the human gene set. Most important structural and functional residues in these homologous regions are maintained, and most changes are conservative rather than drastic. Three quarters of the isoforms produced from tandem duplicated exon substitution events are tissue specific, particularly in nervous and cardiac tissues, and tandem duplicated exon substitution events are enriched in functional terms related to structures in the brain and skeletal muscle. Considerable evidence was found for the convergent evolution of tandem duplicated exon substitution events in vertebrates, arthropods and nematodes. Twelve human gene families have orthologues with tandem duplicated exon substitution events in both Drosophila melanogaster and Caenorhabditis elegans. Six of these gene families are ion transporters, suggesting that tandem exon duplication in genes that control the flow of ions into the cell has an adaptive benefit. The ancient origins, the strong indications of tissue-specific functions, and the evidence of convergent evolution suggest that these events may have played important roles in the evolution of animal tissues and organs (Martinez-Gomez, 2022).

    The Gain and Loss of Cryptochrome/Photolyase Family Members during Evolution

    The cryptochrome/photolyase (CRY/PL) family represents an ancient group of proteins fulfilling two fundamental functions. While photolyases repair UV-induced DNA damages, cryptochromes mainly influence the circadian clock. This study took advantage of the large number of already sequenced and annotated genes available in databases and systematically searched for the protein sequences of CRY/PL family members in all taxonomic groups primarily focusing on metazoans and limiting the number of species per taxonomic order to five. Using BLASTP searches and subsequent phylogenetic tree and motif analyses, five distinct photolyases (CPDI, CPDII, CPDIII, 6-4 photolyase, and the plant photolyase PPL) and six cryptochrome subfamilies (DASH-CRY, mammalian-type MCRY, Drosophila-type DCRY, cnidarian-specific ACRY, plant-specific PCRY, and the putative magnetoreceptor CRY4) were identified. Manually assigning the CRY/PL subfamilies to the species studied, it was noted that over evolutionary history, an initial increase of various CRY/PL subfamilies was followed by a decrease and specialization. Thus, in more primitive organisms (e.g., bacteria, archaea, simple eukaryotes, and in basal metazoans), relatively few CRY/PL members are found. As species become more evolved (e.g., cnidarians, mollusks, echinoderms, etc.), the CRY/PL repertoire also increases, whereas it appears to decrease again in more recent organisms (humans, fruit flies, etc.). Moreover, this study indicates that all cryptochromes, although largely active in the circadian clock, arose independently from different photolyases, explaining their different modes of action (Deppisch, 2022).

    Copy number changes in co-expressed odorant receptor genes enable selection for sensory differences in drosophilid species

    Despite numerous examples of chemoreceptor gene family expansions and contractions, how these relate to modifications in the sensory neuron populations in which they are expressed remains unclear. Drosophila melanogaster's odorant receptor (Or) family is ideal for addressing this question because most Ors are expressed in distinct olfactory sensory neuron (OSN) types. Between-species changes in Or copy number may therefore indicate increases or reductions in the number of OSN populations. This study investigated the Or67a subfamily, which exhibits copy number variation in D. melanogaster and its closest relatives: D. simulans, D. sechellia and D. mauritiana. These species' common ancestor had three Or67a paralogues that had already diverged adaptively. Following speciation, two Or67a paralogues were lost independently in D. melanogaster and D. sechellia, with ongoing positive selection shaping the intact genes. Unexpectedly, the functionally diverged Or67a paralogues in D. simulans are co-expressed in a single neuron population, which projects to a glomerulus homologous to that innervated by Or67a neurons in D. melanogaster. Thus, while sensory pathway neuroanatomy is conserved, independent selection on co-expressed receptors has contributed to species-specific peripheral coding. This work reveals a type of adaptive change largely overlooked for olfactory evolution, raising the possibility that similar processes influence other cases of insect Or co-expression (Auer, 2022).

    Twenty-seven ZAD-ZNF genes of Drosophila melanogaster are orthologous to the embryo polarity determining mosquito gene cucoid

    The C2H2 zinc finger gene cucoid establishes anterior-posterior (AP) polarity in the early embryo of culicine mosquitoes. This gene is unrelated to genes that establish embryo polarity in other fly species (Diptera), such as the homeobox gene bicoid, which serves this function in the traditional model organism Drosophila melanogaster. The cucoid gene is a conserved single copy gene across lower dipterans but nothing is known about its function in other species, and its evolution in higher dipterans, including Drosophila, is unresolved. This study found that cucoid is a member of the ZAD-containing C2H2 zinc finger (ZAD-ZNF) gene family and is orthologous to 27 of the 91 members of this family in D. melanogaster, including M1BP, ranshi, ouib, nom, zaf1, odj, Nnk, trem, Zif, and eighteen uncharacterized genes. Available knowledge of the functions of cucoid orthologs in Drosophila melanogaster suggest that the progenitor of this lineage specific expansion may have played a role in regulating chromatin. Many aspects of the gene duplication history of cucoid in the brachyceran lineage of D. melanogaster are descri ed, thereby providing a framework for predicting potential redundancies among these genes in D. melanogaster (Li, 2023).

    The origin and structural evolution of de novo genes in Drosophila

    Although previously thought to be unlikely, recent studies have shown that de novo gene origination from previously non-genic sequences is a relatively common mechanism for gene innovation in many species and taxa. These young genes provide a unique set of candidates to study the structural and functional origination of proteins. However, understanding of their protein structures and how these structures originate and evolve are still limited, due to a lack of systematic studies. This study combined high-quality base-level whole genome alignments, bioinformatic analysis, and computational structure modeling to study the origination, evolution, and protein structure of lineage-specific de novo genes. 555 de novo gene candidates were identified in D. melanogaster that originated within the Drosophilinae lineage. A gradual shift was found in sequence composition, evolutionary rates, and expression patterns with their gene ages, which indicates possible gradual shifts or adaptations of their functions. Surprisingly, little overall protein structural changes were found for de novo genes in the Drosophilinae lineage. Using Alphafold2, ESMFold, and molecular dynamics, a number of de novo gene candidates were identified with protein products that are potentially well-folded, many of which are more likely to contain transmembrane and signal proteins compared to other annotated protein-coding genes. Using ancestral sequence reconstruction, it was found that most potentially well-folded proteins are often born folded. Interestingly, one case was observed where disordered ancestral proteins become ordered within a relatively short evolutionary time. Single-cell RNA-seq analysis in testis showed that although most de novo genes are enriched in spermatocytes, several young de novo genes are biased in the early spermatogenesis stage, indicating potentially important but less emphasized roles of early germline cells in the de novo gene origination in testis. This study provides a systematic overview of the origin, evolution, and structural changes of Drosophilinae -specific de novo genes (Peng,2023).

    Identifying candidate de novo genes expressed in the somatic female reproductive tract of Drosophila melanogaster

    Most eukaryotic genes have been vertically transmitted to the present from distant ancestors. However, variable gene number across species indicates that gene gain and loss also occurs. While new genes typically originate as products of duplications and rearrangements of preexisting genes, putative de novo genes-genes born out of ancestrally nongenic sequence-have been identified. Previous studies of de novo genes in Drosophila have provided evidence that expression in male reproductive tissues is common. However, no studies have focused on female reproductive tissues. This study begins addressing this gap in the literature by analyzing the transcriptomes of 3 female reproductive tract organs (spermatheca, seminal receptacle, and parovaria) in 3 species-the focal species, Drosophila melanogaster and 2 closely related species, Drosophila simulans and Drosophila yakuba, with the goal of identifying putative D. melanogaster-specific de novo genes expressed in these tissues. Several candidate genes, located in sequence annotated as intergenic, were discovered. Consistent with the literature, these genes tend to be short, single exon, and lowly expressed. Evidence was also found evidence that some of these genes are expressed in other D. melanogaster tissues and both sexes. The relatively small number of intergenic candidate genes discovered here is similar to that observed in the accessory gland, but substantially fewer than that observed in the testis (Lombardo, 2023).

    Population genomics reveals mechanisms and dynamics of de novo expressed open reading frame emergence in Drosophila melanogaster

    Novel genes are essential for evolutionary innovations and differ substantially even between closely related species. This study sought de novo expressed open reading frames (neORFs), the not-yet fixed precursors of de novo genes that emerged within a single species. Genomes were with long-read technology and the corresponding transcriptomes from inbred lines of Drosophila melanogaster, derived from seven geographically diverse populations. We found line-specific neORFs in abundance but few neORFs shared by lines, suggesting a rapid turnover. Gain and loss of transcription is more frequent than the creation of ORFs, for example, by forming new start and stop codons. Consequently, the gain of ORFs becomes rate limiting and is frequently the initial step in neORFs emergence. Furthermore, transposable elements (TEs) are major drivers for intragenomic duplications of neORFs, yet TE insertions are less important for the emergence of neORFs. However, highly mutable genomic regions around TEs provide new features that enable gene birth. In conclusion, neORFs have a high birth-death rate, are rapidly purged, but surviving neORFs spread neutrally through populations and within genomes (Grandchamp, 2023).

    HP6/Umbrea is dispensable for viability and fertility, suggesting essentiality of newly evolved genes is rare

    The newly evolved gene Heterochromatin Protein 6 (HP6), which has been previously classified as essential, challenged the dogma that functions required for viability are only seen in genes with a long evolutionary history. Based on previous RNA-sequencing analysis in Drosophila germ cells, it was asked whether HP6 might play a role in germline development. Surprisingly, it was found that CRISPR-generated HP6 mutants are viable and fertile. Using previously generated mutants, an independent lethal allele and an RNAi off-target effect were identified that prevented accurate interpretation of HP6 essentiality. By reviewing existing data, it was found that the vast majority of young genes that were previously classified as essential were indeed viable when tested with orthologous methods. Together, these data call into question the frequency with which newly evolved genes gain essential functions and suggest that using multiple independent genetic methods is essential when probing the functions of young genes (Grill, 2023).

    Evolution of male genitalia in the Drosophila repleta species group (Diptera: Drosophilidae)

    The Drosophila repleta group comprises more than one hundred species that inhabit several environments in the Neotropics and use different hosts as rearing and feeding resources. Rather homogeneous in their external morphology, they are generally distinguished by the male genitalia, seemingly their fastest evolving morphological trait, constituting an excellent model to study patterns of genital evolution in the context of a continental adaptive radiation. Although much is known about the evolution of animal genitalia at population level, surveys on macroevolutionary scale of this phenomenon are scarce. This study used a suite of phylogenetic comparative methods to elucidate the macroevolutionary patterns of genital evolution through deep time and large continental scales. The results indicate that male genital size and some aspects of shape have been evolving by speciational evolution, probably due to the microevolutionary processes involved in species mate recognition. In contrast, several features of the aedeagus (loosely compared to the penis) shape seemed to have evolved in a gradual fashion, with heterogeneous evolutionary phenotypic rates among clades. In general, the tempo of the evolution of aedeagus morphology was constant from the origin of the group until the Pliocene, when it accelerated in some clades that diversified mainly in this period. The incidence of novel ecological conditions in the tempo of aedeagus evolution and the relationship between species mate recognition and speciation in the Drosophila repleta group are discussed (Stefanini, 2021).

    Ancestral male recombination in Drosophila albomicans produced geographically restricted neo-Y chromosome haplotypes varying in age and onset of decay

    Male Drosophila typically have achiasmatic meiosis, and fusions between autosomes and the Y chromosome have repeatedly created non-recombining neo-Y chromosomes that degenerate. Intriguingly, Drosophila nasuta males recombine, but their close relative D. albomicans reverted back to achiasmy after evolving neo-sex chromosomes. This study used genome-wide polymorphism data to reconstruct the complex evolutionary history of neo-sex chromosomes in D. albomicans and examine the effect of recombination and its cessation on the initiation of neo-Y decay. Population and phylogenomic analyses reveal three distinct neo-Y types that are geographically restricted. Due to ancestral recombination with the neo-X, overall nucleotide diversity on the neo-Y is similar to the neo-X but severely reduced within neo-Y types. Consistently, the neo-Y chromosomes fail to form a monophyletic clade in sliding window trees outside of the region proximal to the fusion. Based on tree topology changes, the recombination breakpoints were infered that produced haplotypes specific to each neo-Y type. Recombination became suppressed at different time points for the different neo-Y haplotypes. Haplotype age correlates with onset of neo-Y decay, and older neo-Y haplotypes show more fixed gene disruption via frameshift indels and down-regulation of neo-Y alleles. Genes are downregulated independently on the different neo-Ys, but are depleted of testes-expressed genes across all haplotypes. This indicates that genes important for male function are initially shielded from degeneration. Thesee results offer a time course of the early progression of Y chromosome evolution, showing how the suppression of recombination, through the reversal to achiasmy in D. albomicans males, initiates the process of degeneration (Wei, 2019).

    Seasonal changes in recombination characteristics in a natural population of Drosophila melanogaster

    Environmental seasonality is a potent evolutionary force, capable of maintaining polymorphism, promoting phenotypic plasticity and causing bet-hedging. In Drosophila, environmental seasonality has been reported to affect life-history traits, tolerance to abiotic stressors and immunity. Oscillations in frequencies of alleles underlying fitness-related traits were also documented alongside SNPs across the genome. This study tested for seasonal changes in two recombination characteristics, crossover rate and crossover interference, in a natural D. melanogaster population from India using morphological markers of the three major chromosomes. Winter flies, collected after the dry season, have significantly higher desiccation tolerance than their autumn counterparts. This difference proved to hold also for hybrids with three independent marker stocks, suggesting its genetic rather than plastic nature. Significant between-season changes are documented for crossover rate (in 9 of 13 studied intervals) and crossover interference (in four of eight studied pairs of intervals); both single and double crossovers were usually more frequent in the winter cohort. The winter flies also display weaker plasticity of both recombination characteristics to desiccation. The observed differences are ascribed to indirect selection on recombination caused by directional selection on desiccation tolerance. These findings suggest that changes in recombination characteristics can arise even after a short period of seasonal adaptation (~8-10 generations) (Aggarwal, 2021).

    Variation in fine scale recombination rate in temperature-evolved Drosophila melanogaster populations in response to selection. G3 (Bethesda)

    Meiotic recombination plays a critical evolutionary role in maintaining fitness in response to selective pressures due to changing environments. Variation in recombination rate has been observed amongst and between species and populations and within genomes across numerous taxa. Studies have demonstrated a link between changes in recombination rate and selection, but the extent to which fine scale recombination rate varies between evolved populations during the evolutionary period in response to selection is under active research. This study utilize a set of three temperature-evolved Drosophila melanogaster populations that were shown to have diverged in several phenotypes, including recombination rate, based on the temperature regime in which they evolved. Using whole genome sequencing data from these populations, LD-based fine scale recombination maps wee generated for each population. With these maps, recombination rates and patterns were comparedamong the three populations; they have diverged at fine scales but are conserved at broader scales. A correlation was was further demonstrated between recombination rates and genomic variation in the three populations. Lastly, variation was shown in localized regions of enhanced recombination rates, termed warm-spots, between the populations with these warm-spots and associated genes overlapping areas previously shown to have diverged in the three populations due to selection. These data support the existence of recombination modifiers in these populations which are subject to selection during evolutionary change (Winbush, 2022).

    Variation in mutation, recombination, and transposition rates in Drosophila melanogaster and Drosophila simulans

    The rates of mutation, recombination, and transposition are core parameters in models of evolution. They impact genetic diversity, responses to ongoing selection, and levels of genetic load. However, even for key evolutionary model species such as Drosophila melanogaster and D. simulans, few estimates of these parameters are available, and little idea is available of how rates vary between individuals, sexes, or populations. Knowledge of this variation is fundamental for parameterizing models of genome evolution. This study provides direct estimates of mutation, recombination, and transposition rates and their variation in a West African and a European population of D. melanogaster and a European population of D. simulans. Across 89 flies, 58 single nucleotide mutations, 286 crossovers, and 89 transposable elements (TE) insertions were observed. Compared to the European D. melanogaster, the West African population had a lower mutation rate (1.67 vs. 4.86 × 10-9 site-1 gen-1) and a lower transposition rate (8.99 vs. 23.36 × 10-5 copy-1 gen-1), but a higher recombination rate (3.44 vs. 2.06 cM/Mb). The European D. simulans population has a similar mutation rate to European D. melanogaster, but a significantly higher recombination rate and a lower, but not significantly different, transposition rate. Overall, paternal-derived mutations were found to be more frequent than maternal ones in both species. This study quantifies the variation in rates of mutation, recombination, and transposition among different populations and sexes, and the direct estimate of these parameters in D. melanogaster and D. simulans will benefit future studies in population and evolutionary genetics (Wang, 2023).

    Structure of the Transcriptional Regulatory Network Correlates with Regulatory Divergence in Drosophila

    Transcriptional control of gene expression is regulated by biochemical interactions between cis-regulatory DNA sequences and trans-acting factors that form complex regulatory networks. Genetic changes affecting both cis- and trans-acting sequences in these networks have been shown to alter patterns of gene expression as well as higher-order organismal phenotypes. This study investigated how the structure of these regulatory networks relates to patterns of polymorphism and divergence in gene expression. To do this, a transcriptional regulatory network inferred for Drosophila melanogaster was compared to differences in gene regulation observed between two strains of D. melanogaster as well as between two pairs of closely related species: Drosophila sechellia and Drosophila simulans, and D. simulans and D. melanogaster. The number of transcription factors predicted to directly regulate a gene ("in-degree") was negatively correlated with divergence in both gene expression (mRNA abundance) and cis-regulation. This observation suggests that the number of transcription factors directly regulating a gene's expression affects the conservation of cis-regulation and gene expression over evolutionary time. The hypothesis that transcription factors regulating more target genes (higher "out-degree") are less likely to evolve changes in their cis-regulation and expression (presumably due to increased pleiotropy) was also tested, but little support was found for this predicted relationship. Taken together, these data show how the architecture of regulatory networks can influence regulatory evolution (Yang, 2017).

    Cis- and trans-regulatory effects on gene expression in a natural population of Drosophila melanogaster

    Cis- and trans-regulatory mutations are important contributors to transcriptome evolution. Quantifying their relative contributions to intraspecific variation in gene expression is essential for understanding the population genetic processes that underlie evolutionary changes in gene expression. This study has examined this issue by quantifying genome-wide allele specific expression (ASE) variation using a crossing scheme that produces F1 hybrids between 18 different Drosophila melanogaster strains sampled from the Drosophila Genetic Reference Panel (DGRP) and a reference strain from another population. Head and body samples from F1 adult females were subjected to RNA-seq and the subsequent ASE quantification. Cis- and trans-regulatory effects on expression variation were estimated from these data. A higher proportion of genes showed significant cis-regulatory variation (~28%) than those showed significant trans-regulatory variation (~9%). The sizes of cis-regulatory effects on expression variation were 1.98 and 1.88 times larger than trans-regulatory effects in heads and bodies, respectively. A generalized linear model analysis revealed that both cis- and trans-regulated expression variation was strongly associated with nonsynonymous nucleotide diversity and tissue specificity. Interestingly, trans-regulated variation showed a negative correlation with local recombination rate. Also, analysis on proximal transposon element (TE) insertions suggested that they affect transcription levels of ovary-expressed genes more pronouncedly than genes not expressed in the ovary, possibly due to defense mechanisms against TE mobility in the germline. Collectively, this detailed quantification of ASE variations from a natural population has revealed a number of new relationships between genomic factors and the effects of cis- and trans-regulatory factors on expression variation (Osada, 2017).

    Pigmentation pattern and developmental constraints: flight muscle attachment sites delimit the thoracic trident of Drosophila melanogaster

    In their seminal paper published in 1979, Gould and Lewontin argued that some traits arise as by-products of the development of other structures and not for direct utility in themselves. This study shows that this applies to the trident, a pigmentation pattern observed on the thorax of Drosophila melanogaster. Using reporter constructs, it was shown that the expression domain of several genes encoding pigmentation enzymes follows the trident shape. This domain is complementary to the expression pattern of stripe (sr), which encodes an essential transcription factor specifying flight muscle attachment sites. sr limits the expression of these pigmentation enzyme genes to the trident by repressing them in its own expression domain, i.e. at the flight muscle attachment sites. Evidence is given that repression of not only yellow but also other pigmentation genes, notably tan, is involved in the trident shape. The flight muscle attachment sites and sr expression patterns are remarkably conserved in dipterans reflecting the essential role of sr. The data suggest that the trident is a by-product of flight muscle attachment site patterning that arose when sr was co-opted for the regulation of pigmentation enzyme coding genes (Gibert, 2018).

    A major role for noncoding regulatory mutations in the evolution of enzyme activity

    The quantitative evolution of protein activity is a common phenomenon, yet we know little about any general mechanistic tendencies that underlie it. For example, an increase (or decrease) in enzyme activity may evolve from changes in protein sequence that alter specific activity, or from changes in gene expression that alter the amount of protein produced. The latter in turn could arise via mutations that affect gene transcription, posttranscriptional processes, or copy number. To determine the types of genetic changes underlying the quantitative evolution of protein activity, this study dissected the basis of ecologically relevant differences in Alcohol dehydrogenase (Adh) enzyme activity between and within several Drosophila species. By using recombinant Adh transgenes to map the functional divergence of ADH enzyme activity in vivo, this study found that amino acid substitutions explain only a minority (0 to 25%) of between- and within-species differences in enzyme activity. Instead, noncoding substitutions that occur across many parts of the gene (enhancer, promoter, and 5' and 3' untranslated regions) account for the majority of activity differences. Surprisingly, one substitution in a transcriptional Initiator element has occurred in parallel in two species, indicating that core promoters can be an important natural source of the tuning of gene activity. Furthermore, both regulatory and coding substitutions were found to contribute to fitness (resistance to ethanol toxicity). Although qualitative changes in protein specificity necessarily derive from coding mutations, these results suggest that regulatory mutations may be the primary source of quantitative changes in protein activity, a possibility overlooked in most analyses of protein evolution (Loehlin, 2019).

    Holding it together: rapid evolution and positive selection in the synaptonemal complex of Drosophila

    The synaptonemal complex (SC) is a highly conserved meiotic structure that functions to pair homologs and facilitate meiotic recombination in most eukaryotes. Five Drosophila SC proteins have been identified and localized within the complex: C(3)G, C(2)M, CONA, ORD, and the newly identified Corolla. The SC is required for meiotic recombination in Drosophila and absence of these proteins leads to reduced crossing over and chromosomal nondisjunction. The proteins display little apparent sequence conservation outside the genus. To identify factors that explain this lack of apparent conservation, a molecular evolutionary analysis of these genes was performed across the Drosophila genus. For the five SC components, gene sequence similarity declines rapidly with increasing phylogenetic distance and only ORD and C(2)M are identifiable outside of the Drosophila genus. SC gene sequences have a higher dN/dS (omega) rate ratio than the genome wide average and this can in part be explained by the action of positive selection in almost every SC component. Omega estimates for the five SC components are in accordance with their physical position within the SC. Components interacting with chromatin evolve slowest and components comprising the central elements evolve the most rapidly. Thus, the Drosophila SC is proposed to be evolving rapidly due to two combined effects: 1) a high rate of evolution can be partly explained by low purifying selection on protein components whose function is to simply hold chromosomes together, 2) positive selection in the SC is driven by its sex-specificity combined with its role in facilitating both recombination and centromere clustering in the face of recurrent bouts of drive in female meiosis (Hemmer, 2016).

    Genomic and transcriptomic associations identify a new insecticide resistance phenotype for the selective sweep at the Cyp6g1 locus of Drosophila melanogaster

    Scans of the Drosophila melanogaster genome have identified organophosphate resistance loci among those with the most pronounced signature of positive selection. In this study the molecular basis of resistance to the organophosphate insecticide azinphos-methyl was investigated using the Drosophila Genetic Reference Panel and genome-wide association. Recently released full transcriptome data was used to extend the utility of the Drosophila Genetic Reference Panel resource beyond traditional genomewide association studies to allow systems genetics analyses of phenotypes. Both genomic and transcriptomic associations independently identified Cyp6g1, a gene involved in resistance to DDT and neonicotinoid insecticides, as the top candidate for azinphos-methyl resistance. This was verified by transgenically overexpressing Cyp6g1 using natural regulatory elements from a resistant allele, resulting in a 6.5-fold increase in resistance. Four novel candidate genes associated with azinphos-methyl resistance were found, all of which are involved in either regulation of fat storage or nervous system development. In Cyp6g1, a demonstrable resistance locus was found, a verification that transcriptome data can be used to identify variants associated with insecticide resistance, and an overlap was found between peaks of a genome-wide association study and a genome-wide selective sweep analysis (Battlay, 2015).

    Rapid divergence and convergence of life-history in experimentally evolved Drosophila melanogaster

    Laboratory
    selection experiments are alluring in their simplicity, power, and ability to inform about how evolution works. A longstanding challenge facing evolution experiments with metazoans is that significant generational turnover takes a long time. This study presents data from a unique system of experimentally evolved laboratory populations of Drosophila melanogaster that have experienced three distinct life-history selection regimes. The goal of the study was to determine how quickly populations of a certain selection regime diverge phenotypically from their ancestors, and how quickly they converge with independently derived populations that share a selection regime. Results indicate that phenotypic divergence from an ancestral population occurs rapidly, within dozens of generations, regardless of that population's evolutionary history. Similarly, populations sharing a selection treatment converge on common phenotypes in this same time frame, regardless of selection pressures those populations may have experienced in the past. These patterns of convergence and divergence were found to emerge much faster than expected, suggesting that intermediate evolutionary history has transient effects in this system. These results are applicable to other experimental evolution projects, and suggest that many relevant questions can be sufficiently tested on shorter timescales than previously thought (Burke, 2016).

    Survey of global genetic diversity within the Drosophila immune system

    Numerous studies across a wide range of taxa have demonstrated that immune genes are routinely among the most rapidly evolving genes in the genome. This observation, however, does not address what proportion of immune genes undergo strong selection during adaptation to novel environments. This study determined the extent of very recent divergence in genes with immune function across five populations of Drosophila melanogaster;t immune genes do not show an overall trend of recent rapid adaptation. The population-based approach uses a set of carefully matched control genes to account for the effects of demography and local recombination rate, allowing identification of whether specific immune functions are putative targets of strong selection. Evidence was found that viral defense genes are rapidly evolving in Drosophila at multiple time scales. Local adaptation to bacteria and fungi is less extreme and primarily occurs through changes in recognition and effector genes rather than large-scale changes to the regulation of the immune response. Surprisingly, genes in the Toll pathway, which show a high rate of adaptive substitutions between the D. melanogaster and D. simulans lineages, show little population differentiation. Quantifying the flies for resistance to a generalist Gram-positive bacterial pathogen, it was found that this genetic pattern of low population differentiation was recapitulated at the phenotypic level. In sum, these results highlight the complexity of immune evolution and suggest that Drosophila immune genes do not follow a uniform trajectory of strong directional selection as flies encounter new environments (Early, 2016).

    Genome-wide analysis of long-term evolutionary domestication in Drosophila melanogaster

    Experimental evolutionary genomics now allows biologists to test fundamental theories concerning the genetic basis of adaptation. This laboratory conducted one of the longest laboratory evolution experiments with any sexually-reproducing metazoan, Drosophila melanogaster. Next-generation resequencing data from this experiment was conducted to examine genome-wide patterns of genetic variation over an evolutionary time-scale that approaches 1,000 generations. Measures of variation within and differentiation between populations were compared to simulations based on a variety of evolutionary scenarios. This analysis yielded no clear evidence of hard selective sweeps, whereby natural selection acts to increase the frequency of a newly-arising mutation in a population until it becomes fixed. Evidence was found for selection acting on standing genetic variation, as independent replicate populations exhibit similar population-genetic dynamics, without obvious fixation of candidate alleles under selection. A hidden-Markov model test for selection also found widespread evidence for selection. More genetic variation was found genome-wide, and less differentiation was found between replicate populations genome-wide, than arose in any of the simulated evolutionary scenarios (Phillips, 2016).

    Variation in the intensity of selection on codon bias over time causes contrasting patterns of base composition evolution in Drosophila

    Four-fold degenerate coding sites form a major component of the genome, and are often used to make inferences about selection and demography, so that understanding their evolution is important. Despite previous efforts, many questions regarding the causes of base composition changes at these sites in Drosophila remain unanswered. To shed further light on this issue, a new whole-genome polymorphism dataset was obtained from D. simulans. Samples were analyzed from the putatively ancestral range of D. simulans, as well as an existing polymorphism dataset from an African population of D. melanogaster. By using D. yakuba as an outgroup, clear evidence was found for selection on 4-fold sites along both lineages over a substantial period, with the intensity of selection increasing with GC content. Based on an explicit model of base composition evolution, it is suggested that the observed AT-biased substitution pattern in both lineages is probably due to an ancestral reduction in selection intensity, and is unlikely to be the result of an increase in mutational bias towards AT alone. By using two polymorphism-based methods for estimating selection coefficients over different timescales, it was shown that the selection intensity on codon usage has been rather stable in D. simulans in the recent past, but the long-term estimates in D. melanogaster are much higher than the short-term ones, indicating a continuing decline in selection intensity, to such an extent that the short-term estimates suggest that selection is only active in the most GC-rich parts of the genome. Finally, evidence is provided for complex evolutionary patterns in the putatively neutral short introns, which cannot be explained by the standard GC-biased gene conversion model. These results reveal a dynamic picture of base composition evolution (Jackson, 2017).

    A variable genetic architecture of melanic evolution in Drosophila melanogaster

    Unraveling the genetic architecture of adaptive phenotypic divergence is a fundamental quest in evolutionary biology. In Drosophila melanogaster, high-altitude melanism has evolved in separate mountain ranges in sub-Saharan Africa, potentially as an adaptation to UV intensity. The genetic basis of this melanism was investigated in three populations using a new bulk segregant analysis mapping method. Nineteen distinct QTL regions were identified from 9 mapping crosses, with several QTL peaks overlapping between two or all populations, and yet different crosses involving the same melanic population commonly yielded distinct QTLs. The strongest QTLs often overlapped well-known pigmentation genes, but wide signals of genetic differentiation (FST) was typically not found between lightly and darkly pigmented populations at these genes. Instead, small numbers of highly differentiated SNPs were found at the probable causative genes. A simulation analysis showed that these patterns of polymorphism were consistent with selection on standing genetic variation. Overall, these results suggest that even for potentially simpler traits like pigmentation, the complexity of adaptive trait evolution poses important challenges for QTL mapping and population genetic analysis (Bastide, 2016).

    Promoter shape varies across populations and affects promoter evolution and expression noise

    Animal promoters initiate transcription either at precise positions (narrow promoters) or dispersed regions (broad promoters), a distinction referred to as promoter shape. Although highly conserved, the functional properties of promoters with different shapes and the genetic basis of their evolution remain unclear. This study used natural genetic variation across a panel of 81 Drosophila lines to measure changes in transcriptional start site (TSS) usage, identifying thousands of genetic variants affecting transcript levels (strength) or the distribution of TSSs within a promoter (shape). The results identify promoter shape as a molecular trait that can evolve independently of promoter strength. Broad promoters typically harbor shape-associated variants, with signatures of adaptive selection. Single-cell measurements demonstrate that variants modulating promoter shape often increase expression noise, whereas heteroallelic interactions with other promoter variants alleviate these effects. These results uncover new functional properties of natural promoters and suggest the minimization of expression noise as an important factor in promoter evolution (Schor, 2016).

    Predictable phenotypic, but not karyotypic, evolution of populations with contrasting initial history

    The relative impact of selection, chance and history will determine the predictability of evolution. There is a lack of empirical research on this subject, particularly in sexual organisms. This study used experimental evolution to test the predictability of evolution. The real-time evolution was analyzed of Drosophila subobscura populations derived from contrasting European latitudes placed in a novel laboratory environment. Each natural population was sampled twice within a three-year interval. Evolutionary responses at both phenotypic (life-history, morphological and physiological traits) and karyotypic levels were studied for around 30 generations of laboratory culture. The results show (1) repeatable historical effects between years in the initial state, at both phenotypic and karyotypic levels; (2) predictable phenotypic evolution with general convergence except for body size; and (3) unpredictable karyotypic evolution. It is concluded that the predictability of evolution is contingent on the trait and level of organization, highlighting the importance of studying multiple biological levels with respect to evolutionary patterns (Simoes, 2017).

    Naturally-segregating variation at Ugt86Dd contributes to nicotine resistance in Drosophila melanogaster

    Identifying the sequence polymorphisms underlying complex trait variation is a key goal of genetics research, since knowing the precise causative molecular events allows insight into the pathways governing trait variation. Genetic analysis of complex traits in model systems regularly starts by constructing QTL maps, but generally fails to identify causative sequence polymorphisms. Previous studies mapped a series of QTL contributing to resistance to nicotine in a Drosophila melanogaster multiparental mapping resource, and this study use a battery of functional tests to resolve QTL to the molecular level. One large-effect QTL resided over a cluster of UDP-glucuronosyltransferases, and quantitative complementation tests using deficiencies eliminating subsets of these detoxification genes revealed allelic variation impacting resistance. RNAseq showed that Ugt86Dd had significantly higher expression in genotypes that are more resistant to nicotine, and anterior midgut-specific RNAi of this gene reduced resistance. A segregating 22-bp frameshift deletion in Ugt86Dd, and accounting for the InDel during mapping largely eliminates the QTL, implying the event explains the bulk of the effect of the mapped locus. CRISPR/Cas9 editing a relatively resistant genotype to generate lesions in Ugt86Dd that recapitulate the naturally-occurring putative loss-of-function allele leads to a large reduction in resistance. Despite this major effect of the deletion, the allele appears to be very rare in wild-caught populations, and likely explains only a small fraction of the natural variation for the trait. Nonetheless, this putatively causative coding InDel can be a launchpad for future mechanistic exploration of xenobiotic detoxification (Highfill, 2017).

    The genetic basis of susceptibility to low-dose paraquat and variation between the sexes in D. melanogaster

    Toxicant resistance is a complex trait, affected both by genetics and the environment. Like most complex traits, it can exhibit sexual dimorphism, yet sex is often overlooked as a factor in studies of toxicant resistance. Paraquat, one such toxicant, is a commonly used herbicide and is known to produce mitochondrial oxidative stress, decrease dopaminergic neurons and dopamine (DA) levels, and decrease motor ability. The purpose of this study was to map the genes contributing to low-dose paraquat susceptibility in Drosophila melanogaster, and to determine if susceptibility differs between the sexes. One hundred of the Drosophila Genetic Reference Panel (DGRP) lines were scored for susceptibility via climbing ability and used in a genome wide association study (GWAS). Variation in seventeen genes in females and thirty-five genes in males associated with paraquat susceptibility. Only two candidate genes overlapped between the sexes despite a significant positive correlation between male and female susceptibilities. Many associated polymorphisms had significant interactions with sex, with most having conditionally neutral effects. Conditional neutrality between the sexes likely stems from sex-biased expression which may result from partial resolution of sexual conflict. Candidate genes were verified with RNAi knockdowns, gene expression analyses, and DA quantification. Several of these genes are novel associations with paraquat susceptibility. This research highlights the importance of assessing both sexes when studying toxicant susceptibility (Lovejoy, 2021).

    Multiple P450s and variation in neuronal genes underpins the response to the insecticide Imidacloprid in a population of Drosophila melanogaster

    Insecticide resistance is an economically important example of evolution in response to intense selection pressure. In this study, the genetics of resistance to the neonicotinoid insecticide imidacloprid is explored using the Drosophila Genetic Reference Panel, a collection of inbred Drosophila melanogaster genotypes derived from a single population in North Carolina. Imidacloprid resistance varied substantially among genotypes, and more resistant genotypes tended to show increased capacity to metabolize and excrete imidacloprid. Variation in resistance level was then associated with genomic and transcriptomic variation, implicating several candidate genes involved in central nervous system function and the cytochrome P450s Cyp6g1 and Cyp6g2. CRISPR-Cas9 mediated removal of Cyp6g1 suggested that it contributed to imidacloprid resistance only in backgrounds where it was already highly expressed. Cyp6g2, previously implicated in juvenile hormone synthesis via expression in the ring gland, was shown to be expressed in metabolically relevant tissues of resistant genotypes. Cyp6g2 overexpression was shown to both metabolize imidacloprid and confer resistance. These data collectively suggest that imidacloprid resistance is influenced by a variety of previously known and unknown genetic factors (Denecke, 2017).

    Nearly neutral evolution across the Drosophila melanogaster genome

    Under the nearly neutral theory of molecular evolution, the proportion of effectively neutral mutations is expected to depend upon the effective population size (Ne). This study investigate whether this is the case across the genome of Drosophila melanogaster using polymorphism data from North American and African lines. This study shows that the ratio of the number of nonsynonymous and synonymous polymorphisms is negatively correlated to the number of synonymous polymorphisms, even when the nonindependence is accounted for. The relationship is such that the proportion of effectively neutral nonsynonymous mutations increases by approximately 45% as Ne is halved. However, it was also shown that this relationship is steeper than expected from an independent estimate of the distribution of fitness effects from the site frequency spectrum. A number of potential explanations for this was investigated, and it was shown, using simulation, that this is consistent with a model of genetic hitchhiking: Genetic hitchhiking depresses diversity at neutral and weakly selected sites, but has little effect on the diversity of strongly selected sites (Castellano, 2018).

    Pleiotropy modulates the efficacy of selection in Drosophila melanogaster

    Pleiotropy is the well-established idea that a single mutation affects multiple phenotypes. If a mutation has opposite effects on fitness when expressed in different contexts, then genetic conflict arises. Pleiotropic conflict is expected to reduce the efficacy of selection by limiting the fixation of beneficial mutations through adaptation, and the removal of deleterious mutations through purifying selection. While this has been widely discussed, in particular in the context of a putative "gender load", it has yet to be systematically quantified. This work empirically estimates to which extent different pleiotropic regimes impede the efficacy of selection in Drosophila melanogaster. Whole-genome polymorphism data from a single African population and divergence data from D. simulans were used to estimate the fraction of adaptive fixations (alpha), the rate of adaptation (omegaA) and the direction of selection (DoS). After controlling for confounding covariates, it was found that the different pleiotropic regimes have a relatively small, but significant, effect on selection efficacy. Specifically, the results suggest that pleiotropic sexual antagonism may restrict the efficacy of selection, but that this conflict can be resolved by limiting the expression of genes to the sex where they are beneficial. Intermediate levels of pleiotropy across tissues and life stages can also lead to maladaptation in D. melanogaster, due to inefficient purifying selection combined with low frequency of mutations that confer a selective advantage. Thus, this study highlights the need to consider the efficacy of selection in the context of antagonistic pleiotropy, and of genetic conflict in general (Fraisse, 2018).

    Adaptation to developmental diet influences the response to selection on age at reproduction in the fruit fly

    Experimental evolution (EE) is a powerful tool for addressing how environmental factors influence life-history evolution. While in nature different selection pressures experienced across the lifespan shape life histories, EE studies typically apply selection pressures one at a time. This study assesses the consequences of adaptation to three different developmental diets in combination with classical selection for early or late reproduction in the fruit fly Drosophila melanogaster. Response to each selection pressure is similar to that observed when they are applied independently, but the overall magnitude of the response depends on the selection regime experienced in the other life stage. For example, adaptation to increased age at reproduction increased lifespan across all diets, however, the extent of the increase was dependent on the dietary selection regime. Similarly, adaptation to a lower calorie developmental diet led to faster development and decreased adult weight, but the magnitude of the response was dependent on the age-at-reproduction selection regime. Given that multiple selection pressures are prevalent in nature, these findings suggest that trade-offs should be considered not only among traits within an organism, but also among adaptive responses to different - sometimes conflicting - selection pressures, including across life stages (May, 2019).

    Stage-specific genotype-by-environment interactions for cold and heat hardiness in Drosophila melanogaster

    Environments often vary across a life cycle, imposing fluctuating natural selection across development. Such fluctuating selection can favor different phenotypes in different life stages, but stage-specific evolutionary responses will depend on genetic variance, covariance, and their interaction across development and across environments. Thus, quantifying how genetic architecture varies with plastic responses to the environment and across development is vital to predict whether stage-specific adaptation will occur in nature. Additionally, the interaction of genetic variation and environmental plasticity (GxE) may be stage-specific, leading to a three-way interaction between genotype, environment, and development or GxDxE. To test for these patterns, larvae and adults of Drosophila melanogaster isogenic lines derived from a natural population were exposed to extreme heat and cold stress after developmental acclimation to cool (18 degrees C) and warm (25 degrees C) conditions, and genetic variance for thermal hardiness was measured. Significant GxE was observed that was specific to larvae and adults for cold and heat hardiness (GxDxE), but no significant genetic correlation across development for either trait at either acclimation temperature. However, cross-development phenotypic correlations for acclimation responses suggest that plasticity itself may be developmentally constrained, though rigorously testing this hypothesis requires more experimentation. These results illustrate the potential for stage-specific adaptation within a complex life cycle and demonstrate the importance of measuring traits at appropriate developmental stages and environmental conditions when predicting evolutionary responses to changing climates (Freda, 2019).

    Cross-sex genetic covariances limit the evolvability of wing-shape within and among species of Drosophila

    The independent evolution of males and females is potentially constrained by both sexes inheriting the same alleles from their parents. This genetic constraint can limit the evolvability of complex traits; however, there are few studies of multivariate evolution that incorporate cross-sex genetic covariances in their predictions. Drosophila wing-shape has emerged as a model high-dimensional phenotype; wing-shape is highly evolvable in contemporary populations, and yet perplexingly stable across phylogenetic timescales. This study shows that cross-sex covariances in D. melanogaster, given by the B-matrix, may considerably bias wing-shape evolution. Using random skewers, this study shows that B would constrain the response to antagonistic selection by 90%, on average, but would double the response to concordant selection. Both cross-sex within-trait and cross-sex cross-trait covariances determined the predicted response to antagonistic selection, but only cross-sex within-trait covariances facilitated the predicted response to concordant selection. Similar patterns were observed in the direction of extant sexual dimorphism in D. melanogaster, and in directions of most and least dimorphic variation across the Drosophila phylogeny. These results highlight the importance of considering between-sex genetic covariances when making predictions about evolution on both macro- and micro- evolutionary timescales, and may provide one more explanatory piece in the puzzle of stasis (Sztepanacz, 2019).

    Quantifying selection on standard metabolic rate and body mass in Drosophila melanogaster

    Standard metabolic rate (SMR), defined as the minimal energy expenditure required for self-maintenance, is a key physiological trait. Few studies have estimated its relationship with fitness, most notably in insects. This is presumably due to the difficulty of measuring SMR in a large number of very small individuals. Using high-throughput flow-through respirometry and a Drosophila melanogaster laboratory population adapted to a life-cycle that facilitates fitness measures, SMR, body mass, and fitness were quantified in 515 female and 522 male adults. A novel multivariate approach was used to estimate linear and non-linear selection differentials and gradients from the variance-covariance matrix of fitness, SMR, and body mass, allowing traits specific covariates to be accommodated within a single model. In males, linear selection differentials for mass and SMR were positive and individually significant. Selection gradients were also positive but, despite substantial sample sizes, were non-significant due to increased uncertainty given strong SMR-mass collinearity. In females, only nonlinear selection was detected and it appeared to act primarily on body size, although the individual gradients were again non-significant. Selection did not differ significantly between sexes although differences in the fitness surfaces suggest sex-specific selection as an important topic for further study (Videlier, 2020).

    Sexual antagonism, temporally fluctuating selection, and variable dominance affect a regulatory polymorphism in Drosophila melanogaster

    Understanding how genetic variation is maintained within species is a major goal of evolutionary genetics that can shed light on the preservation of biodiversity. This study examined the maintenance of a regulatory single-nucleotide polymorphism (SNP) of the X-linked Drosophila melanogaster gene fezzik. The derived variant at this site is at intermediate frequency in many worldwide populations, but absent in populations from the ancestral species range in sub-Saharan Africa. Wild-caught individuals from a single European population were collected and genotyped biannually over a period of five years, revealing an overall difference in allele frequency between the sexes and a consistent change in allele frequency across seasons in females but not in males. Modelling based on the observed allele and genotype frequencies suggested that both sexually antagonistic and temporally fluctuating selection may help maintain variation at this site. The derived variant is predicted to be female-beneficial and mostly recessive; however, there was uncertainty surrounding the dominance estimates, and long-term modelling projections suggest that it is more likely to be dominant. By examining gene expression phenotypes, it was found that phenotypic dominance was variable and dependent upon developmental stage and genetic background, suggesting that dominance may be variable at this locus. It was further determined that fezzik expression and genotype are associated with starvation resistance in a sex-dependent manner, suggesting a potential phenotypic target of selection. By characterizing the mechanisms of selection acting on this SNP, the results improve understanding of how selection maintains genetic and phenotypic variation in natural populations (Glaser-Schmitt, 2021).

    Divergent natural selection alters male sperm competition success in Drosophila melanogaster

    Sexually selected traits may also be subject to non-sexual selection. If optimal trait values depend on environmental conditions, then "narrow sense" (i.e., non-sexual) natural selection can lead to local adaptation, with fitness in a certain environment being highest among individuals selected under that environment. Such adaptation can, in turn, drive ecological speciation via sexual selection. To date, most research on the effect of narrow-sense natural selection on sexually selected traits has focused on precopulatory measures like mating success. However, postcopulatory traits, such as sperm function, can also be under non-sexual selection, and have the potential to contribute to population divergence between different environments. This study investigated the effects of narrow-sense natural selection on male postcopulatory success in Drosophila melanogaster. Two extreme environments, low oxygen (10%, hypoxic) or high CO(2) (5%, hypercapnic) were chosen to detect small effects. The sperm defensive (P1) and offensive (P2) capabilities of selected and control males were measured in the corresponding selection environment and under control conditions. Overall, selection under hypoxia decreased both P1 and P2, while selection under hypercapnia had no effect. Surprisingly, P1 for both selected and control males was higher under both ambient hypoxia and ambient hypercapnia, compared to control conditions, while P2 was lower under hypoxia. Limited evidence was found for local adaptation: the positive environmental effect of hypoxia on P1 was greater in hypoxia-selected males than in controls. The implications of our findings for the evolution of postcopulatory traits in response to non-sexual and sexual selection (Dobler, 2022).

    Adaptation of Drosophila melanogaster to Long Photoperiods of High-Latitude Summers Is Facilitated by the ls-Timeless Allele

    Circadian clocks help animals to be active at the optimal time of the day whereby for most species the daily light-dark cycle is the most important zeitgeber for their circadian clock. In this respect, long arctic summer days are particularly challenging as light is present almost 24 h per day, and continuous light makes the circadian clocks of many animals arrhythmic. This is especially true for the fruit fly, Drosophila melanogaster, which possesses a very light-sensitive clock. The blue-light photoreceptor Cryptochrome (CRY) and the clock protein Timeless (TIM) are the light-sensitive components of the circadian clock and are responsible for constant light-induced arrhythmicity even at very low light intensities. Nevertheless, D. melanogaster was able to spread from its tropical origin and invade northern latitudes. This study tested whether a natural polymorphism at the timeless (tim) locus, s-tim and ls-tim, helped adaptation to very long photoperiods. The recently evolved natural allele, ls-tim, encodes a longer, less light sensitive form of TIM (L-TIM) in addition to the shorter (S-TIM) form, the only form encoded by the ancient s-tim allele. ls-tim has evolved in southeastern Italy and slowly spread to higher latitudes. L-TIM is known to interact less efficiently with CRY as compared with S-TIM. The locomotor activity patterns of ~40 wild s-tim and ls-tim isofemale lines caught at different latitudes was measured under simulated high-latitude summer light conditions (continuous light or long photoperiods with 20-h daily light). It was found that the ls-tim lines were significantly more rhythmic under continuous light than the s-tim lines. Importantly, the ls-tim lines can delay their evening activity under long photoperiods, a behavioral adaptation that appears to be optimal under high-latitude conditions. These observations suggest that the functional gain associated with ls-tim may drive the northern spread of this allele by directional selection (Deppisch, 2022).

    Contribution of cryptochromes and photolyases for insect life under sunlight

    The cryptochrome/photolyase (CRY/PL) family is essential for life under sunlight because photolyases repair UV-damaged DNA and cryptochromes are normally part of the circadian clock that controls the activity-sleep cycle within the 24-h day. This study aimed to understand how the lineage and habitat of an insect affects its CRY/PL composition. To this end, the large number of annotated protein sequences of 340 insect species already available in databases was searched for CRY/PLs. Using phylogenetic tree and motif analyses, four frequent CRY/PLs in insects: the photolyases 6-4 PL and CPDII PL were identified, as well as the mammalian-type cryptochrome (MCRY) and Drosophila-type cryptochrome (DCRY). Assignment of CRY/PLs to the corresponding insects confirmed that light-exposed insects tend to have more CRY/PLs than insects with little light exposure. Nevertheless, even insects with greatly reduced CRY/PLs still possess MCRY, which can be regarded as the major insect cryptochrome. Only flies of the genus Schizophora, which includes Drosophila melanogaster, lost MCRY. Moreover, MCRY and CPDII PL as well as DCRY and 6-4 PL were fount to occur very frequently together, suggesting an interaction between the two pairs (Deppisch, 2023).

    Heterogeneity in effective size across the genome: effects on the inverse instantaneous coalescence rate (IICR) and implications for demographic inference under linked selection

    The relative contribution of selection and neutrality in shaping species genetic diversity is one of the most central and controversial questions in evolutionary theory. Genomic data provide growing evidence that linked selection, i.e. the modification of genetic diversity at neutral sites through linkage with selected sites, might be pervasive over the genome. Several studies proposed that linked selection could be modeled as first approximation by a local reduction (e.g. purifying selection, selective sweeps) or increase (e.g. balancing selection) of effective population size (Ne). At the genome-wide scale, this leads to variations of Ne from one region to another, reflecting the heterogeneity of selective constraints and recombination rates between regions. This study investigated the consequences of such genomic variations of Ne on the genome-wide distribution of coalescence times. The underlying motivation concerns the impact of linked selection on demographic inference, because the distribution of coalescence times is at the heart of several important demographic inference approaches. Using the concept of inverse instantaneous coalescence rate, it was demonstrated that in a panmictic population, linked selection always results in a spurious apparent decrease of Ne along time. Balancing selection has a particularly large effect, even when it concerns a very small part of the genome. More general models were studied including genuine population size changes, population structure or transient selection, and the effect of linked selection was found to be significantly reduced by that of population structure. The models and conclusions presented in this study are also relevant to the study of other biological processes generating apparent variations of Ne along the genome (Boitard, 2022).

    No major cost of evolved survivorship in Drosophila melanogaster populations coevolving with Pseudomonas entomophila

    Rapid exaggeration of host and pathogen traits via arms race dynamics is one possible outcome of host-pathogen coevolution. However, the exaggerated traits are expected to incur costs in terms of resource investment in other life-history traits. The current study investigated the costs associated with evolved traits in a host-pathogen coevolution system. The Drosophila melanogaster (host)-Pseudomonas entomophila (pathogen) system was used to experimentally derive two selection regimes, one where the host and pathogen both coevolved, and the other, where only the host evolved against a non-evolving pathogen. After 17 generations of selection, it was found that hosts from both selected populations had better post-infection survivorship than controls. Even though the coevolving populations tended to have better survivorship post-infection, no clear evidence that the two selection regimes were significantly different from each other. There was weak evidence for the coevolving pathogens being more virulent than the ancestral pathogen. No major cost was found of increased post-infection survivorship. The costs were not different between the coevolving hosts and the hosts evolving against a non-evolving pathogen. No evolved costs were found in the coevolving pathogens. Thus, these results suggest that increased host immunity and pathogen virulence may not be costly (Ahlawat, 2022).

    Selection on inversion breakpoints favors proximity to pairing sensitive sites in Drosophila melanogaster

    Chromosomal inversions are widespread among taxa, and have been implicated in a number of biological processes including adaptation, sex chromosome evolution, and segregation distortion. Consistent with selection favoring linkage between loci, it is well established that length is a selected trait of inversions. However, the factors that affect the distribution of inversion breakpoints remain poorly understood. 'Sensitive sites' have been mapped on all euchromatic chromosome arms in Drosophila melanogaster, and may be a source of natural selection on inversion breakpoint positions. Briefly, sensitive sites are genomic regions wherein proximal structural rearrangements result in large reductions in local recombination rates in heterozygotes. This study shows that breakpoints of common inversions are significantly more likely to lie within a cytological band containing a sensitive site than are breakpoints of rare inversions. Furthermore, common inversions for which neither breakpoint intersects a sensitive site are significantly longer than rare inversions, but common inversions whose breakpoints intersect a sensitive site show no evidence for increased length. These results are interpreted to mean that selection favors inversions whose breakpoints disrupt synteny near to sensitive sites, possibly because these inversions suppress recombination in large genomic regions. This is the first evidence consistent with positive selection acting on inversion breakpoint positions (Corbett-Detig, 2016).

    A genomic map of the effects of linked selection in Drosophila

    Natural selection at one site shapes patterns of genetic variation at linked sites. Quantifying the effects of 'linked selection' on levels of genetic diversity is key to making reliable inference about demography, building a null model in scans for targets of adaptation, and learning about the dynamics of natural selection. This study introduced the first method that jointly infers parameters of distinct modes of linked selection, notably background selection and selective sweeps, from genome-wide diversity data, functional annotations and genetic maps. The central idea is to calculate the probability that a neutral site is polymorphic given local annotations, substitution patterns, and recombination rates. Information is then combined across sites and samples using composite likelihood in order to estimate genome-wide parameters of distinct modes of selection. In addition to parameter estimation, this approach yields a map of the expected neutral diversity levels along the genome. To illustrate the utility of this approach, it was applied to genome-wide resequencing data from 125 lines in Drosophila melanogaster and diversity levels was reliably predicted at the 1Mb scale. The results corroborate estimates of a high fraction of beneficial substitutions in proteins and untranslated regions (UTR). They allow distinguishing between the contribution of sweeps and other modes of selection around amino acid substitutions and uncovered evidence for pervasive sweeps in untranslated regions (UTRs). This inference further suggests a substantial effect of other modes of linked selection and of adaptation in particular. More generally, it was demonstrated that linked selection has had a larger effect in reducing diversity levels and increasing their variance in D. melanogaster than previously appreciated (Elyashiv, 2016).

    Single-molecule sequencing resolves the detailed structure of complex satellite DNA loci in Drosophila melanogaster

    Highly repetitive satellite DNA (satDNA) repeats are found in most eukaryotic genomes. SatDNAs are rapidly evolving and have roles in genome stability and chromosome segregation. Their repetitive nature poses a challenge for genome assembly and makes progress on the detailed study of satDNA structure difficult. This study used single-molecule sequencing long reads from Pacific Biosciences (PacBio) to determine the detailed structure of all major autosomal complex satDNA loci in Drosophila melanogaster, with a particular focus on the 260-bp and Responder satellites. The optimal de novo assembly methods and parameter combinations were determined that were required to produce a high-quality assembly of these previously unassembled satDNA loci and validate this assembly using molecular and computational approaches. It was determined that the computationally intensive PBcR-BLASR assembly pipeline yielded better assemblies than the faster and more efficient pipelines based on the MHAP hashing algorithm, and it is essential to validate assemblies of repetitive loci. The assemblies reveal that satDNA repeats are organized into large arrays interrupted by transposable elements. The repeats in the center of the array tend to be homogenized in sequence, suggesting that gene conversion and unequal crossovers lead to repeat homogenization through concerted evolution, although the degree of unequal crossing over may differ among complex satellite loci. Evidence was found for higher-order structure within satDNA arrays that suggest recent structural rearrangements. These assemblies provide a platform for the evolutionary and functional genomics of satDNAs in pericentric heterochromatin (Khost, 2017).

    High rate of translocation-based gene birth on the Drosophila Y chromosome

    The Y chromosome is a unique genetic environment defined by a lack of recombination and male-limited inheritance. The Drosophila Y chromosome has been gradually acquiring genes from the rest of the genome, with only seven Y-linked genes being gained over the past 63 million years (0.12 gene gains per million years). Using a next-generation sequencing (NGS)-powered genomic scan, this study shows that gene transfers to the Y chromosome are much more common than previously suspected: at least 25 have arisen across three Drosophila species over the past 5.4 million years (1.67 per million years for each lineage). The gene transfer rate is significantly lower in Drosophila melanogaster than in the Drosophila simulans clade, primarily due to Y-linked retrotranspositions being significantly more common in the latter. Despite all Y-linked gene transfers being evolutionarily recent (<1 million years old), only three showed evidence for purifying selection (omega </= 0.14). Thus, although the resulting Y-linked functional gene acquisition rate (0.25 new genes per million years) is double the longer-term estimate, the fate of most new Y-linked genes is defined by rapid degeneration and pseudogenization. These results show that Y-linked gene traffic, and the molecular mechanisms governing these transfers, can diverge rapidly between species, revealing the Drosophila Y chromosome to be more dynamic than previously appreciated. This analytical method provides a powerful means to identify Y-linked gene transfers and will help illuminate the evolutionary dynamics of the Y chromosome in Drosophila and other species (Tobler, 2017).

    MicroRNA clusters integrate evolutionary constraints on expression and target affinities: the miR-6/5/4/286/3/309 cluster in Drosophila

    A striking feature of microRNAs is that they are often clustered in the genomes of animals. The functional and evolutionary consequences of this clustering remain obscure. This study investigated a microRNA cluster miR-6/5/4/286/3/309 that is conserved across drosophilid lineages. Small RNA sequencing revealed expression of this microRNA cluster in Drosophila melanogaster leg discs, and conditional overexpression of the whole cluster resulted in leg appendage shortening. Transgenic overexpression lines expressing different combinations of microRNA cluster members were also constructed. Expression of individual microRNAs from the cluster resulted in a normal wild-type phenotype, but either the expression of several ancient microRNAs together (miR-5/4/286/3/309) or more recently evolved clustered microRNAs (miR-6-1/2/3) can recapitulate the phenotypes generated by the whole-cluster overexpression. Screening of transgenic fly lines revealed down-regulation of leg patterning gene cassettes in generation of the leg-shortening phenotype. Furthermore, cell transfection with different combinations of microRNA cluster members revealed a suite of downstream genes targeted by all cluster members, as well as complements of targets that are unique for distinct microRNAs. Considered together, the microRNA targets and the evolutionary ages of each microRNA in the cluster demonstrates the importance of microRNA clustering, where new members can reinforce and modify the selection forces on both the cluster regulation and the gene regulatory network of existing microRNAs (Qu, 2020).

    A Rapid Evolving microRNA Cluster Rewires Its Target Regulatory Networks in Drosophila

    New miRNAs are evolutionarily important but their functional evolution remains unclear. This study reports that the evolution of a microRNA cluster, mir-972C rewires its downstream regulatory networks in Drosophila. Genomic analysis reveals that mir-972C originated in the common ancestor of Drosophila where it comprises six old miRNAs. It has subsequently recruited six new members in the melanogaster subgroup after evolving for at least 50 million years. Both the young and the old mir-972C members evolved rapidly in seed and non-seed regions. Combining target prediction and cell transfection experiments, this study found that the seed and non-seed changes in individual mir-972C members cause extensive target divergence among D. melanogaster, D. simulans, and D. virilis, consistent with the functional evolution of mir-972C reported recently. Intriguingly, the target pool of the cluster as a whole remains relatively conserved. These results suggest that clustering of young and old miRNAs broadens the target repertoires by acquiring new targets without losing many old ones. This may facilitate the establishment of new miRNAs in existing regulatory networks (Lyu, 2021).

    Drosophila as a useful model for understanding the evolutionary physiology of obesity resistance and metabolic thrift

    Evolved metabolic thriftiness in humans is a proposed contributor to the obesity epidemic. Insect models have been shown to evolve both 'metabolic thrift' in response to rearing on high-protein diets that promote leanness, and 'obesity resistance' when reared on fattening high-carbohydrate, low-protein foods. Despite the hypothesis that human obesity is caused by evolved metabolic thrift, genetic contributions to this physiological trait remain elusive. A pilot study was conducted to determine whether thrift and obesity resistance can arise under laboratory based 'quasi-natural selection' in the genetic model organism Drosophila melanogaster. Both these traits were found to evolve within 16 generations. Contrary to predictions from the 'thrifty genotype/phenotype' hypothesis, this study found that when animals from a metabolic thrift inducing high-protein environment are mismatched to fattening high-carbohydrate foods, they did not become 'obese'. Rather, they accumulate less triglyceride than control animals, not more. It is speculated that this may arise through as yet un-quantified parental effects - potentially epigenetic. This study establishes that D. melanogaster could be a useful model for elucidating the role of the trans- and inter-generational effects of diet on the genetics of metabolic traits in higher animals (Gray, 2021).

    The pdm3 locus is a hotspot for recurrent evolution of female-limited color dimorphism in Drosophila

    Sex-limited polymorphisms are an intriguing form of sexual dimorphism that offer unique opportunities to reconstruct the evolutionary changes that decouple male and female traits encoded by a shared genome. This study investigated the genetic basis of a Mendelian female-limited color dimorphism (FLCD) that segregates in natural populations of more than 20 species of the Drosophila montium subgroup. In these species, females have alternative abdominal color morphs, light and dark, whereas males have only one color morph in each species. A comprehensive molecular phylogeny of the montium subgroup supports multiple origins of FLCD. Despite this, FLCD mapped to the same locus in four distantly related species-the transcription factor POU domain motif 3 (pdm3), which acts as a repressor of abdominal pigmentation in D. melanogaster. In D. serrata, FLCD maps to a structural variant in the first intron of pdm3; however, this variant is not found in the three other species-D. kikkawai, D. leontia, and D. burlai-and sequence analysis strongly suggests the pdm3 alleles responsible for FLCD originated independently at least three times. It is proposed that cis-regulatory changes in pdm3 form sexually dimorphic and monomorphic alleles that segregate within species and are preserved, at least in one species, by structural variation. Surprisingly, pdm3 has not been implicated in the evolution of sex-specific pigmentation outside the montium subgroup, suggesting that the genetic paths to sexual dimorphism may be constrained within a clade but variable across clades (Yassin, 2016).

    Mapping QTL contributing to variation in posterior lobe morphology between strains of Drosophila melanogaster

    Closely-related, and otherwise morphologically similar insect species frequently show striking divergence in the shape and/or size of male genital structures, a phenomenon thought to be driven by sexual selection. Comparative interspecific studies can help elucidate the evolutionary forces acting on genital structures to drive this rapid differentiation. However, genetic dissection of sexual trait divergence between species is frequently hampered by the difficulty generating interspecific recombinants. Intraspecific variation can be leveraged to investigate the genetics of rapidly-evolving sexual traits; this study carried out out a genetic analysis of variation in the posterior lobe within D. melanogaster. The lobe is a male-specific process emerging from the genital arch of D. melanogaster and three closely-related species, is essential for copulation, and shows radical divergence in form across species. There is also abundant variation within species in the shape and size of the lobe, and while this variation is considerably more subtle than that seen among species, it nonetheless provides the raw material for QTL mapping. An advanced intercross population was created from a pair of phenotypically-different inbred strains, and after phenotyping and genotyping-by-sequencing the recombinants, several QTL contributing to various measures of lobe morphology were mapped. The additional generations of crossing over in the mapping population led to QTL intervals that are smaller than is typical for an F2 mapping design. The intervals that were mapped overlap with a pair of lobe QTL that was previously identified in an independent mapping cross, potentially suggesting a level of shared genetic control of trait variation. The QTL additionally implicate a suite of genes that have been shown to contribute to the development of the posterior lobe. These loci are strong candidates to harbor naturally-segregating sites contributing to phenotypic variation within D. melanogaster, and may also be those contributing to divergence in lobe morphology between species (Hackett, 2006).

    Sex-specific selection and sex-biased gene expression in humans and flies

    Sexual dimorphism results from sex-biased gene expression, which evolves when selection acts differently on males and females. While there is an intimate connection between sex-biased gene expression and sex-specific selection, few empirical studies have studied this relationship directly. This study compare the two on a genome-wide scale in humans and flies. A distinctive "Twin Peaks" pattern in humans that relates the strength of sex-specific selection, quantified by genetic divergence was yound between male and female adults at autosomal loci, to the degree of sex-biased expression. Genes with intermediate degrees of sex-biased expression show evidence of ongoing sex-specific selection, while genes with either little or completely sex-biased expression do not. This pattern apparently results from differential viability selection in males and females acting in the current generation. The Twin Peaks pattern is also found in Drosophila using a different measure of sex-specific selection acting on fertility. A simple model was developed that successfully recapitulates the Twin Peaks. These results suggest that many genes with intermediate sex-biased expression experience ongoing sex-specific selection in humans and flies (Cheng, 2016).

    Sexual selection shapes development and maturation rates in Drosophila

    Explanations for the evolution of delayed maturity usually invoke trade-offs mediated by growth, but processes of reproductive maturation continue long after growth has ceased. This study tested whether sexual selection shapes the rate of posteclosion maturation in the fruit fly Drosophila melanogaster. Populations maintained for more than 100 generations under a short generation time and polygamous mating system evolved faster posteclosion maturation and faster egg-to-adult development of males, when compared to populations kept under short generations and randomized monogamy that eliminated sexual selection. An independent assay demonstrated that more mature males have higher fitness under polygamy, but this advantage disappears under monogamy. In contrast, for females greater maturity was equally advantageous under polygamy and monogamy. Furthermore, monogamous populations evolved faster development and maturation of females relative to polygamous populations, with no detectable trade-offs with adult size or egg-to-adult survival. These results suggest that a major aspect of male maturation involves developing traits that increase success in sexual competition, whereas female maturation is not limited by investment in traits involved in mate choice or defense against male antagonism. Moreover, rates of juvenile development and adult maturation can readily evolve in opposite directions in the two sexes, possibly implicating polymorphisms with sexually antagonistic pleiotropy (Hollis, 2016).

    Sex-biased transcriptome divergence along a latitudinal gradient

    Sex-dependent gene expression is likely an important genomic mechanism that allows sex-specific adaptation to environmental changes. Among Drosophila species, sex-biased genes display remarkably consistent evolutionary patterns; male-biased genes evolve faster than unbiased genes in both coding sequence and expression level, suggesting sex differences in selection through time. However, comparatively little is known of the evolutionary process shaping sex-biased expression within species. Latitudinal clines offer an opportunity to examine how changes in key ecological parameters also influence sex-specific selection and the evolution of sex-biased gene expression. This study assayed male and female gene expression in Drosophila serrata along a latitudinal gradient in eastern Australia spanning most of its endemic distribution. Analysis of 11,631 genes across eight populations revealed strong sex differences in the frequency, mode and strength of divergence. Divergence was far stronger in males than females and while latitudinal clines were evident in both sexes, male divergence was often population specific, suggesting responses to localized selection pressures that do not covary predictably with latitude. While divergence was enriched for male-biased genes, there was no overrepresentation of X-linked genes in males. By contrast, X-linked divergence was elevated in females, especially for female-biased genes. Many genes that diverged in D. serrata have homologs also showing latitudinal divergence in Drosophila simulans and Drosophila melanogaster on other continents, likely indicating parallel adaptation in these distantly related species. These results suggest that sex differences in selection play an important role in shaping the evolution of gene expression over macro- and micro-ecological spatial scales (Allen, 2017).

    The large X-effect on secondary sexual characters and the genetics of variation in sex comb tooth number in Drosophila subobscura

    This study examined the genetics of a secondary sexual trait, male sex comb size in Drosophila subobscura, to evaluate the amount of variation attributable to the X-chromosome. This species bears unusually large sex combs for its species group, and therefore, this trait may be a good candidate for having been affected by natural or sexual selection. Significant heritable variation was observed in number of teeth of the distal sex comb across strains. While reciprocal F1 crosses seemed to implicate a disproportionate X-chromosome effect, further examination in the F2 progeny showed that transgressive autosomal effects inflated the estimate of variation associated with the X-chromosome in the F1. Instead, the X-chromosome appears to confer the smallest contribution of all major chromosomes to the observed phenotypic variation. Further, effects on copulation latency or duration associated with the observed phenotypic variation were not observed. Overall, this study presents an examination of the genetics underlying segregating phenotypic variation within species and illustrates two common pitfalls associated with some past studies of the genetic basis of secondary sexual traits (Mittleman, 2017).

    Direct benefits of choosing a high fitness mate can offset the indirect costs associated with intralocus sexual conflict

    Intralocus sexual conflict generates a cost to mate choice: high fitness partners transmit genetic variation that confers lower fitness to offspring of the opposite sex. Earlier work in the fruit fly, Drosophila melanogaster, revealed that these indirect genetic costs were sufficient to reverse potential "good genes" benefits of sexual selection. However, mate choice can also confer direct fitness benefits by inducing larger numbers of progeny. This study considers whether direct benefits through enhanced fertility could offset the costs associated with intralocus sexual conflict in D. melanogaster. Using hemiclonal analysis, it was found that females mated to high fitness males produced 11% more offspring compared to those mated to low fitness males, and high fitness females produced 37% more offspring than low fitness females. These direct benefits more than offset the reduction in offspring fitness caused by intralocus sexual conflict, creating a net fitness benefit for each sex to pairing with a high fitness partner. These findings highlight the need to consider both direct and indirect effects when investigating the fitness impacts of mate choice. Direct fitness benefits may shelter sexually antagonistic alleles from selection, suggesting a novel mechanism for the maintenance of fitness variation (Pischedda, 2017).

    Evolutionary dynamics of male reproductive genes in the Drosophila virilis subgroup

    Postcopulatory sexual selection (PCSS) is a potent evolutionary force that can drive rapid changes of reproductive genes within species, and thus has the potential to generate reproductive incompatibilities between species. Male seminal fluid proteins (SFPs) are major players in postmating interactions, and are important targets of PCSS in males. The virilis subgroup of Drosophila exhibits strong interspecific gametic incompatibilities, and can serve as a model to study the genetic basis of PCSS and gametic isolation. However, reproductive genes in this group have not been characterized. This study utilized short-read RNA sequencing of male reproductive organs to examine the evolutionary dynamics of reproductive genes in members of the virilis subgroup: D. americana, D. lummei, D. novamexicana, and D. virilis. The majority of male reproductive transcripts are testes-biased, accounting for ~15% of all annotated genes. Ejaculatory bulb-biased transcripts largely code for lipid metabolic enzymes, and contain orthologs of the D. melnaogaster ejaculatory bulb protein, Peb-me, which is involved in mating-plug formation. In addition, 71 candidate SFPs were identified, and this gene set was show to have the highest rate of nonsynonymous codon substitution relative to testes- and ejaculatory bulb-biased genes. Furthermore, orthologs were identified of 35 D. melanogaster SFPs that have conserved accessory gland expression in the virilis group. Finally, several of the SFPs that have the highest rate of nonsynonymous codon substitution were shown to reside on chromosomal regions that contribute to paternal gametic incompatibility between species. These results show that SFPs rapidly diversify in the virilis group, and suggest that they likely play a role in PCSS and/or gametic isolation (Ahmed-Braimah, 2017).

    Reproductive isolation through experimental manipulation of sexually antagonistic coevolution in Drosophila melanogaster

    Promiscuity can drive the evolution of sexual conflict before and after mating occurs. Post mating, the male ejaculate can selfishly manipulate female physiology, leading to a chemical arms race between the sexes. Theory suggests that drift and sexually antagonistic coevolution can cause allopatric populations to evolve different chemical interactions between the sexes, thereby leading to postmating reproductive barriers and speciation. There is, however, little empirical evidence supporting this form of speciation. This theory was tested by creating an experimental evolutionary model of Drosophila melanogaster populations undergoing different levels of interlocus sexual conflict. Allopatric populations under elevated sexual conflict were shown to exhibit assortative mating, indicating premating reproductive isolation. Further, these allopatric populations also show reduced copulation duration and sperm defense ability when mating happens between individuals across populations compared to that within the same population, indicating postmating prezygotic isolation. Sexual conflict can cause reproductive isolation in allopatric populations through the coevolution of chemical (postmating prezygotic) as well as behavioural (premating) interactions between the sexes. Thus it study provides the first comprehensive evidence of postmating (as well as premating) reproductive isolation due to sexual conflict (Syed, 2017).

    Male relatedness and familiarity are required to modulate male-induced harm to females in Drosophila

    Males compete over mating and fertilization, and often harm females in the process. Inclusive fitness theory predicts that increasing relatedness within groups of males may relax competition and discourage male harm of females as males gain indirect benefits. Recent studies in Drosophila melanogaster are consistent with these predictions, and have found that within-group male relatedness increases female fitness, though others have found no effects. Importantly, these studies did not fully disentangle male genetic relatedness from larval familiarity, so the extent to which modulation of harm to females is explained by male familiarity remains unclear. This study performed a fully factorial design, isolating the effects of male relatedness and larval familiarity on female harm. While no differences were found in male courtship or aggression, there was a significant interaction between male genetic relatedness and familiarity on female reproduction and survival. Relatedness among males increased female lifespan, reproductive lifespan and overall reproductive success, but only when males were familiar. By showing that both male relatedness and larval familiarity are required to modulate female harm, these findings reconcile previous studies, shedding light on the potential role of indirect fitness effects on sexual conflict and the mechanisms underpinning kin recognition in fly populations (Le Page, 2017).

    A species-specific multigene family mediates differential sperm displacement in Drosophila melanogaster

    Sperm competition is a postcopulatory selection mechanism in species in which females mate with multiple males. Despite its evolutionary relevance in shaping male traits, the genetic mechanisms underlying sperm competition are poorly understood. A recently originated multigene family specific to Drosophila melanogaster, Sdic, is important for the outcome of sperm competition in doubly mated females, although the mechanistic nature of this phenotype remained unresolved. This study compared doubly mated females, second mated to either Sdic knockout or nonknockout males, and directly visualize sperm dynamics in the female reproductive tract. A less effective removal of first-to-mate male's sperm within the female's sperm storage organs is consistent with a reduced sperm competitive ability of the Sdic knockout males. These results highlight the role young genes can play in driving the evolution of sperm competition (Jayaswal, 2018).

    Precopulatory but not postcopulatory male reproductive traits diverge in response to mating system manipulation in Drosophila melanogaster

    Competition between males creates potential for pre- and postcopulatory sexual selection and conflict. Theory predicts that males facing risk of sperm competition should evolve traits to secure their reproductive success. If those traits are costly to females, the evolution of such traits may also increase conflict between the sexes. Conversely, under the absence of sperm competition, one expectation is for selection on male competitive traits to relax thereby also relaxing sexual conflict. Experimental evolution studies are a powerful tool to test this expectation. Studies in multiple insect species have yielded mixed and partially conflicting results. This study evaluated male competitive traits and male effects on female costs of mating in Drosophila melanogaster after replicate lines evolved for more than 50 generations either under enforced monogamy or sustained polygamy, thus manipulating the extent of intrasexual competition between males. In a setting where males competed directly with a rival male for access to a female and fertilization of her ova, polygamous males had superior reproductive success compared to monogamous males. When comparing reproductive success solely in double mating standard sperm competition assays, however, no difference was found in male sperm defense competitiveness between the different selection regimes. Instead, monogamous males were found to be inferior in precopulatory competition, which indicates that in this system, enforced monogamy relaxed selection on traits important in precopulatory rather than postcopulatory competition. These findings are discussed in the context of findings from previous experimental evolution studies in Drosophila and other invertebrate species (Wensing, 2017).

    Evolving doublesex expression correlates with the origin and diversification of male sexual ornaments in the Drosophila immigrans species group

    Male ornaments and other sex-specific traits present some of the most dramatic examples of evolutionary innovations. Comparative studies of similar but independently evolved traits are particularly important for identifying repeated patterns in the evolution of these traits. Male-specific modifications of the front legs have evolved repeatedly in Drosophilidae and other Diptera. The best understood of these novel structures is the sex comb of Drosophila melanogaster and its close relatives. This study examined the evolution of another male foreleg modification, the sex brush, found in the distantly related Drosophila immigrans species group. Similar to the sex comb, it was found that the origin of the sex brush correlates with novel, spatially restricted expression of the doublesex (dsx) transcription factor, the primary effector of the Drosophila sex determination pathway. The diversity of Dsx expression patterns in the immigrans species group closely reflects the differences in the presence, position, and size of the sex brush. Together with previous work on sex comb evolution, these observations suggest that tissue-specific activation of dsx expression may be a common mechanism responsible for the evolution of sexual dimorphism and particularly for the origin of novel male-specific ornaments (Rice, 2018).

    Evolutionary divergence in competitive mating success through female mating bias for good genes

    Despite heritable variation for univariate sexually selected traits, recent analyses exploring multivariate traits find evidence consistent with the lek paradox in showing no genetic variation available to choosy females, and therefore no genetic benefits of choice. This study used the preferences of Drosophila melanogaster females to exert bidirectional selection on competitive male mating success to test for the presence and nature of genetic variation underlying this multivariate trait. Male mating success diverged between selection regimens, and flies from success-selected lines had a smaller burden of deleterious, recessive mutations that affect egg-to-adult viability, were better sperm competitors (sperm offence), and did not demonstrate reduced desiccation resistance or components of female fitness (traits thought to trade off with attractiveness) relative to flies from failure-selected populations. Mating success remained subject to inbreeding depression in success-selected lines, suggesting that variation in mating success remains, thanks to numerous genes of small effect. Together, these results provide unique evidence for the evolutionary divergence in male mating success, demonstrating that genetic variation is not exhausted along the axis of precopulatory sexual selection and that female mating biases align with the avoidance of bad genes (Dugand, 2018).

    Evolution of sex-biased gene expression and dosage compensation in the eye and brain of Heliconius butterflies

    Differences in behavior and life history traits between females and males are the basis of divergent selective pressures between sexes. It has been suggested that a way for the two sexes to deal with different life history requirements is through sex-biased gene expression. A comparative sex-biased gene expression analysis was performed of the combined eye and brain transcriptome from five Heliconius species, H. charithonia, H. sara, H. erato, H. melpomene and H. doris, representing five of the main clades from the Heliconius phylogeny. The degree of sexual dimorphism in gene expression is not conserved across Heliconius. Most of the sex-biased genes identified in each species are not sex-biased in any other, suggesting that sexual selection might have driven sexually dimorphic gene expression. Only three genes shared sex-biased expression across multiple species: ultraviolet opsin UVRh1 and orthologs of Drosophila Kruppel-homolog 1 and CG9492. It was also observed that in some species female-biased genes have higher evolutionary rates, but in others, male-biased genes show the fastest rates when compared with unbiased genes, suggesting that selective forces driving sex-biased gene evolution in Heliconius act in a sex- and species-specific manner. Furthermore, dosage compensation was found in all the Heliconius tested, providing additional evidence for the conservation of dosage compensation across Lepidoptera. Finally, sex-biased genes are significantly enriched on the Z, a pattern that could be a result of sexually antagonistic selection (Catalan, 2018).

    Evolution of a central neural circuit underlies Drosophila mate preferences

    Courtship rituals serve to reinforce reproductive barriers between closely related species. Drosophila melanogaster and Drosophila simulans exhibit reproductive isolation, owing in part to the fact that D. melanogaster females produce 7,11-heptacosadiene, a pheromone that promotes courtship in D. melanogaster males but suppresses courtship in D. simulans males. This study compared pheromone-processing pathways in D. melanogaster and D. simulans males to define how these sister species endow 7,11-heptacosadiene with the opposite behavioural valence to underlie species discrimination. Males of both species were shown to detect 7,11-heptacosadiene using homologous peripheral sensory neurons, but this signal is differentially propagated to P1 neurons, which control courtship behaviour. A change in the balance of excitation and inhibition onto courtship-promoting neurons transforms an excitatory pheromonal cue in D. melanogaster into an inhibitory cue in D. simulans. These results reveal how species-specific pheromone responses can emerge from conservation of peripheral detection mechanisms and diversification of central circuitry, and demonstrate how flexible nodes in neural circuits can contribute to behavioural evolution (Seeholzer, 2018).

    The sensory periphery has been proposed to be the most evolutionarily labile element of the nervous system, as changes in the expression or tuning of sensory receptors can allow for the emergence of species-specific behaviours without necessitating potentially more complex developmental rewiring of central pathways in the brain. By contrast, the current results suggest that species-specific behavioural responses to 7,11-HD arise through functional alterations in how pheromone signals are propagated through a structurally conserved central circuit that consists of parallel excitatory and feedforward inhibitory branches. By reweighting the balance of excitatory vAB3 and inhibitory mAL signalling to P1 neurons, 7,11-HD is transformed from an excitatory signal that promotes courtship in D. melanogaster males into an inhibitory signal that suppresses courtship in D. simulans males. Although the analysis highlights the importance of this pheromone pathway in shaping species-specific mate preferences, the possibility cannot be excluded that additional inputs to P1 neurons or other targets of mAL and vAB3 neurons also contribute to divergent courtship decisions. Nevertheless, the data suggest that the branched architecture of pheromone-processing pathways serves as a substrate for the evolution of mate preferences, pointing to the potential existence of favourable sites within neural circuits to instantiate adaptive behavioural changes, analogous to how specific nodes within developmental regulatory networks contribute to morphological diversity (Seeholzer, 2018).

    The conserved tuning of Ppk23+ neurons suggests that D. simulans males dedicate this sensory pathway to the detection of a female pheromones, rather than sensing the chemical cues carried by conspecific females. Consistent with this idea, although P1 neurons are sufficient to elicit courtship in D. simulans males, they are not excited by the taste of a D. simulans female. Given that D. simulans cuticular pheromones are sexually monomorphic and offer ambiguous signals for mate recognition, males probably rely on additional sensory inputs for their arousal. Indeed, the fervent courtship exhibited by D. simulans ppk23 mutants towards females of different species demonstrates that D. simulans males can be aroused in the absence of any species-specific excitatory cue. Dienes, such as 7,11-HD, actively suppress this arousal, presumably through recruitment of strong mAL-mediated inhibition via Ppk23+ pathways. Together, these observations reinforce the notion that pheromone communication in Drosophila serves to focus a male's desire, such that flies lacking cuticular pheromones can be inherently attractive and appropriate mate choices are honed by specific inhibitory chemical cues (Seeholzer, 2018).

    Peripheral adaptations are likely to play an important role in the evolution of novel chemical sensitivities. In this case, however, preserving the sensory periphery while varying central circuits provides a mechanism to alter the behavioural valence of a single chemical cue. As D. melanogaster and D. simulans diverged, their reproductive isolation was probably strengthened by the ability of both species to detect the same pheromone but assign it a different meaning through these central circuit modifications. Notably, in D. melanogaster, P1 neuron excitability is regulated by the social history of a male. This suggests that both experience-dependent and evolutionary adaptations may act on the same neural substrate to modify sensory integration and mate choices, similar to how phenotypic plasticity may facilitate morphological evolution35. Therefore, functional reweighting of sensory inputs at flexible nodes in the nervous system, shaped by evolutionary selection or individual experience, may allow for alternative behavioural responses to the same sensory signal (Seeholzer, 2018).

    Rapid evolution of ecological sexual dimorphism driven by resource competition

    Sex differences in ecologically important traits are common in animals and plants, and prompted Darwin to first propose an ecological cause of sexual dimorphism. Despite theoretical plausibility and Darwin's original notion, a role for ecological resource competition in the evolution of sexual dimorphism has never been directly demonstrated and remains controversial. This study used experimental evolution in Drosophila melanogaster to test the hypothesis that resource competition can drive the evolution of sex differences in diet. Following just three generations of adaptation, offspring from flies evolved in low-resource, high-competition environments show elevated sexual dimorphism in diet preference compared to both the ancestor and populations evolved on high-resource availability. This increased sexual dimorphism was the result of divergence in male sucrose intake and female yeast intake consistent with the differential nutritional requirements of the sexes. These results provide the first real-time direct evidence for evolution of sexual dimorphism driven by resource competition (De Lisle, 2023).

    Predicting the evolution of sexual dimorphism in gene expression

    Sexual dimorphism in gene expression is likely to be the underlying source of dimorphism in a variety of traits. Many analyses implicitly make the assumption that dimorphism only evolves when selection favors different phenotypes in the two sexes, although theory makes clear that it can also evolve as an indirect response to other kinds of selection. Furthermore, previous analyses consider the evolution of a single transcript or trait at a time, ignoring the genetic covariance with other transcripts and traits. This study first shows which aspects of the genetic-variance covariance matrix, G, affect dimorphism when these assumptions about selection are relaxed. Gene expression data from Drosophila melanogaster were analyzed with these predictions in mind. Dimorphism of gene expression for individual transcripts shows the signature of both direct selection for dimorphism and indirect responses to selection. To account for the effect of measurement error on evolutionary predictions, a G matrix was estimated for eight linear combinations of expression traits. Sex-specific genetic variances in female- and male-biased transcription, as well as one relatively unbiased combination, were quite unequal, ensuring that most forms of selection on these traits will have large effects on dimorphism. Predictions of response to selection based on the whole G matrix showed that sexually concordant and antagonistic selection are equally capable of changing sexual dimorphism. In addition, the indirect responses of dimorphism due to cross-trait covariances were quite substantial. The assumption that sexual dimorphism in transcription is an adaptation could be incorrect in many specific cases (Houle, 2021).

    The old and the new: discovery proteomics identifies putative novel seminal fluid proteins in Drosophila

    Seminal fluid proteins (SFPs), the non-sperm component of male ejaculates produced by male accessory glands, are viewed as central mediators of reproductive fitness. SFPs effect both male and female post-mating functions and show molecular signatures of rapid adaptive evolution. While SFP identification was historically challenging, advances in label-free quantitative proteomics expands the scope of studying other systems to further advance the field. This study applied label-free quantitative proteomics to identify the accessory gland proteome and secretome in Drosophila pseudoobscura, a close relative of D. melanogaster, and use the dataset to identify both known and putative novel SFPs. Using this approach 163 putative SFPs were identified, 32% of which overlapped with previously identified D. melanogaster SFPs. SFPs with known extracellular annotation evolve more rapidly than other proteins produced by or contained within the accessory gland. These results will further the understanding of the evolution of SFPs and the underlying male accessory gland proteins that mediate reproductive fitness of the sexes (Karr, 2019).

    Males from populations with higher competitive mating success produce sons with lower fitness

    Female mate choice can result in direct benefits to the female or indirect benefits through her offspring. Females can increase their fitness by mating with males whose genes encode increased survivorship and reproductive output. Alternatively, male investment in enhanced mating success may come at the cost of reduced investment in offspring fitness. This study measures male mating success in a mating arena that allows for male-male, male-female and female-female interactions in Drosophila melanogaster. Isofemale line population measurements were used to correlate male mating success with sperm competitive ability, the number of offspring produced and the indirect benefits of the number of offspring produced by daughters and sons. This study finds that males from populations that gain more copulations do not increase female fitness through increased offspring production, nor do these males fare better in sperm competition. Instead, it was found that these populations have a reduced reproductive output of sons, indicating a potential reproductive trade-off between male mating success and offspring quality (Nguyen, 2019).

    Conspecific sperm precedence is reinforced, but postcopulatory sexual selection weakened, in sympatric populations of Drosophila

    Sexual selection can accelerate speciation by driving the evolution of reproductive isolation, but forces driving speciation could also reciprocally feedback on sexual selection. This might be particularly important in the context of 'reinforcement', where selection acts directly to increase prezygotic barriers to reduce the cost of heterospecific matings. Using assays of sperm competition within and between two sister species, a signature of reinforcement is shown where these species interact: populations of Drosophila pseudoobscura that co-occur with sister species D. persimilis have an elevated ability to outcompete heterospecific sperm, consistent with selection for increased postcopulatory isolation. These D. pseudoobscura populations have decreased sperm competitive ability against conspecifics, reducing the opportunity for sexual selection within these populations. These findings demonstrate that direct selection to increase reproductive isolation against other species can compromise the efficacy of sexual selection within species, a collateral effect of reproductive traits responding to heterospecific interactions (Castillo, 2019).

    Selection shapes turnover and magnitude of sex-biased expression in Drosophila gonads

    Sex-biased gene expression is thought to drive the phenotypic differences in males and females in metazoans. Research on sex organs in Drosophila, employing original approaches and multiple-species contrasts, provides a means to gain insights into factors shaping the turnover and magnitude (fold-bias) of sex-biased expression. Using recent RNA-seq data, sex-biased gonadal expression in 10,740 protein coding sequences were examined in four species of Drosophila, D. melanogaster, D. simulans, D. yakuba and D. ananassae (5 to 44 My divergence). Using an approach wherein genes were identified with lineage-specific transitions (LSTs) in sex-biased status (amongst testis-biased, ovary-biased and unbiased; thus, six transition types) standardized to the number of genes with the ancestral state (S-LSTs), and those with clade-wide expression bias status, several key findings were revealed. First, the six categorical types of S-LSTs in sex-bias showed disparate rates of turnover, consistent with differential selection pressures. Second, the turnover in sex-biased status was largely unrelated to cross-tissue expression breadth, suggesting pleiotropy does not restrict evolution of sex-biased expression. Third, the fold-sex-biased expression, for both testis-biased and ovary-biased genes, evolved directionally over time toward higher values, a crucial finding that could be interpreted as a selective advantage of greater sex-bias, and sexual antagonism. Fourth, in terms of protein divergence, genes with LSTs to testis-biased expression exhibited weak signals of elevated rates of evolution (than ovary-biased) in as little as 5 My, which strengthened over time. Moreover, genes with clade-wide testis-specific expression (44 My), a status not observed for any ovary-biased genes, exhibited striking acceleration of protein divergence, which was linked to low pleiotropy. By studying LSTs and clade-wide sex-biased gonadal expression in a multi-species clade of Drosophila, this study describes evidence that interspecies turnover and magnitude of sex-biased expression have been influenced by selection. Further, whilst pleiotropy was not connected to turnover in sex-biased gonadal expression, it likely explains protein sequence divergence (Whittle, 2019b).

    Cis- and trans-acting variants contribute to survivorship in a naive Drosophila melanogaster population exposed to ryanoid insecticides

    Insecticide resistance is a paradigm of microevolution, and insecticides are responsible for the strongest cases of recent selection in the genome of Drosophila melanogaster. This study used a naive population and a novel insecticide class to examine the ab initio genetic architecture of a potential selective response. Genome-wide association studies (GWAS) of chlorantraniliprole susceptibility reveal variation in a gene of major effect, Stretchin Myosin light chain kinase (Strn-Mlck), which was validated with linkage mapping and transgenic manipulation of gene expression. It is proposed that allelic variation in Strn-Mlck alters sensitivity to the calcium depletion attributable to chlorantraniliprole's mode of action. GWAS also reveal a network of genes involved in neuromuscular biology. In contrast, phenotype to transcriptome associations identify differences in constitutive levels of multiple transcripts regulated by cnc, the homolog of mammalian Nrf2. This suggests that genetic variation acts in trans to regulate multiple metabolic enzymes in this pathway. The most outstanding association is with the transcription level of Cyp12d1 which is also affected in cis by copy number variation. Transgenic overexpression of Cyp12d1 reduces susceptibility to both chlorantraniliprole and the closely related insecticide cyantraniliprole. This systems genetics study reveals multiple allelic variants segregating at intermediate frequency in a population that is completely naive to this new insecticide chemistry and it foreshadows a selective response among natural populations to these chemicals (Green, 2019).

    Genome-wide sexually antagonistic variants reveal long-standing constraints on sexual dimorphism in fruit flies

    The evolution of sexual dimorphism is constrained by a shared genome, leading to 'sexual antagonism', in which different alleles at given loci are favoured by selection in males and females. Despite its wide taxonomic incidence, little is known about the identity, genomic location, and evolutionary dynamics of antagonistic genetic variants. To address these deficits, this study used sex-specific fitness data from 202 fully sequenced hemiclonal Drosophila melanogaster fly lines to perform a genome-wide association study (GWAS) of sexual antagonism. Approximately 230 chromosomal clusters of candidate antagonistic single nucleotide polymorphisms (SNPs) were identified. In contradiction to classic theory, no clear evidence was found that the X chromosome is a hot spot for sexually antagonistic variation. Characterising antagonistic SNPs functionally, a large excess of missense variants were found, but there was very little enrichment in terms of gene function. The evolutionary persistence of antagonistic variants was also assessed by examining extant polymorphism in wild D. melanogaster populations and closely related species. Remarkably, antagonistic variants are associated with multiple signatures of balancing selection across the D. melanogaster distribution range and in their sister species D. simulans, indicating widespread and evolutionarily persistent (about 1 million years) genomic constraints on the evolution of sexual dimorphism. Based on these results, it is proposed that antagonistic variation accumulates because of constraints on the resolution of sexual conflict over protein coding sequences, thus contributing to the long-term maintenance of heritable fitness variation (Ruzicka, 2019).

    Testing for local adaptation in adult male and female fitness among populations evolved under different mate competition regimes

    Mating/fertilization success and fecundity are influenced by sexual interactions among individuals, the nature and frequency of which can vary among different environments. The extent of local adaptation for such adult fitness components is poorly understood. This study allowed 63 populations of Drosophila melanogaster to independently evolve in one of three mating environments that alter sexual interactions: one involved enforced monogamy, while the other two permitted polygamy in either structurally simple standard fly vials or in larger "cages" with added complexity. Adult male and female reproductive fitness were measured after 16 and 28 generations, respectively, via full reciprocal transplants. In males, reciprocal local adaptation was observed between the monogamy and simple polygamy treatments, consistent with the evolution of reproductively competitive males under polygamy that perform poorly under monogamy because they harm their only mate. However, males evolved in the complex polygamy treatment performed similarly or better than all other males in all mating environments, consistent with previous results showing higher genetic quality in this treatment. Differences in female fitness were more muted, suggesting selection on females was less divergent across the mating treatments and echoing a common pattern of greater phenotypic and expression divergence in males than females (Testing for local adaptation in adult male and female fitness among populations evolved under different mate competition regimes (Yun, 2019).

    Sexual selection drives the evolution of male wing interference patterns

    The seemingly transparent wings of many insects have recently been found to display unexpected structural coloration. These structural colours (wing interference patterns: WIPs) may be involved in species recognition and mate choice, yet little is known about the evolutionary processes that shape them. Furthermore, to date investigations of WIPs have not fully considered how they are actually perceived by the viewers' colour vision. This study used multispectral digital imaging and a model of Drosophila vision to compare WIPs of male and female Drosophila simulans from replicate populations forced to evolve with or without sexual selection for 68 generations. WIPs modelled in Drosophila vision evolve in response to sexual selection and provide evidence that WIPs correlate with male sexual attractiveness. These findings add a new element to the otherwise well-described Drosophila courtship display and confirm that wing colours evolve through sexual selection (Hawkes, 2019).

    Evolution of mechanisms that control mating in Drosophila males

    Genetically wired neural mechanisms inhibit mating between species because even naive animals rarely mate with other species. These mechanisms can evolve through changes in expression or function of key genes in sensory pathways or central circuits. Gr32a is a gustatory chemoreceptor that, in D. melanogaster, is essential to inhibit interspecies courtship and sense quinine. Similar to D. melanogaster, this study found that D. simulans Gr32a is expressed in foreleg tarsi, sensorimotor appendages that inhibit interspecies courtship, and it is required to sense quinine. Nevertheless, Gr32a is not required to inhibit interspecies mating by D. simulans males. However, and similar to its function in D. melanogaster, Ppk25, a member of the Pickpocket family, promotes conspecific courtship in D. simulans. Together, this study have identified distinct evolutionary mechanisms underlying chemosensory control of taste and courtship in closely related Drosophila species.

    tartan underlies the evolution of Drosophila male genital morphology

    Male genital structures are among the most rapidly evolving morphological traits and are often the only features that can distinguish closely related species. This process is thought to be driven by sexual selection and may reinforce species separation. However, while the genetic bases of many phenotypic differences have been identified, knowledge about the genes underlying evolutionary differences in male genital organs and organ size more generally is still lacking. The claspers (surstyli) are periphallic structures that play an important role in copulation in insects. This study shows that divergence in clasper size and bristle number between Drosophila mauritiana and Drosophila simulans is caused by evolutionary changes in tartan (trn), which encodes a transmembrane leucine-rich repeat domain protein that mediates cell-cell interactions and affinity. There are no fixed amino acid differences in trn between D. mauritiana and D. simulans, but differences in the expression of this gene in developing genitalia suggest that cis-regulatory changes in trn underlie the evolution of clasper morphology in these species. Finally, analyses of reciprocal hemizygotes that are genetically identical, except for the species from which the functional allele of trn originates, determined that the trn allele of D. mauritiana specifies larger claspers with more bristles than the allele of D. simulans. Therefore, this study has identified a gene underlying evolutionary change in the size of a male genital organ, which will help to better understand not only the rapid diversification of these structures, but also the regulation and evolution of organ size more broadly (Hagen, 2019).

    Unravelling the genetic basis for the rapid diversification of male genitalia between Drosophila species

    In the last 240,000 years, males of the Drosophila simulans species clade have evolved striking differences in the morphology of their epandrial posterior lobes and claspers (surstyli). These appendages are used for grasping the female during mating and so their divergence is most likely driven by sexual selection. Mapping studies indicate a highly polygenic and generally additive genetic basis for these morphological differences. However, there is only a limited understanding of the gene regulatory networks that control the development of genital structures and how they evolved to result in this rapid phenotypic diversification. This study used new D. simulans/D. mauritiana introgression lines on chromosome 3L to generate higher resolution maps of posterior lobe and clasper differences between these species. RNA-seq was carried out on the developing genitalia of both species to identify the expressed genes and those that are differentially expressed between the two species. This allowed testing of the function of expressed positional candidates during genital development in D. melanogaster. Several new genes were found to be involved in the development and possibly the evolution of these genital structures, including the transcription factors Hairy and Grunge. Furthermore, it was discovered that during clasper development Hairy negatively regulates tartan (trn), a gene known to contribute to divergence in clasper morphology. Taken together, these results provide new insights into the regulation of genital development and how this has evolved between species (Hagen, 2020).

    No evidence of positive assortative mating for genetic quality in fruit flies

    In sexual populations, the effectiveness of selection will depend on how gametes combine with respect to genetic quality. If gametes with deleterious alleles are likely to combine with one another, deleterious genetic variation can be more easily purged by selection. Assortative mating, where there is a positive correlation between parents in a phenotype of interest such as body size, is often observed in nature, but does not necessarily reveal how gametes ultimately combine with respect to genetic quality itself. This study manipulated genetic quality in fruit fly populations using an inbreeding scheme designed to provide an unbiased measure of mating patterns. While inbred flies had substantially reduced reproductive success, their gametes did not combine with those of other inbred flies more often than expected by chance, indicating a lack of positive assortative mating. Instead, a negative correlation was detected in genetic quality between parents, i.e. disassortative mating, which diminished with age. This pattern is expected to reduce the genetic variance for fitness, diminishing the effectiveness of selection. How mechanisms of sexual selection could produce a pattern of disassortative mating is discussed. This study highlights that sexual selection has the potential to either increase or decrease genetic load (Sharp, 2019).

    Mechanisms of resistance to pathogens and parasites are thought to be costly and thus to lead to evolutionary trade-offs between resistance and life-history traits expressed in the absence of the infective agents. On the other hand, sexually selected traits are often proposed to indicate "good genes" for resistance, which implies a positive genetic correlation between resistance and success in sexual selection. This study shows that experimental evolution of improved resistance to the intestinal pathogen Pseudomonas entomophila in Drosophila melanogaster was associated with a reduction in male sexual success. Males from four resistant populations achieved lower paternity than males from four susceptible control populations in competition with males from a competitor strain, indicating an evolutionary cost of resistance in terms of mating success and/or sperm competition. In contrast, no costs were found in larval viability, larval competitive ability and population productivity assayed under nutritional limitation; together with earlier studies this suggests that the costs of P. entomophila resistance for nonsexual fitness components are negligible. Thus, rather than indicating heritable pathogen resistance, sexually selected traits expressed in the absence of pathogens may be sensitive to costs of resistance, even if no such costs are detected in other fitness traits (Kawecki, 2019).

    Evolution of sexually dimorphic pheromone profiles coincides with increased number of male-specific chemosensory organs in Drosophila prolongata

    Binary communication systems that involve sex-specific signaling and sex-specific signal perception play a key role in sexual selection and in the evolution of sexually dimorphic traits. The driving forces and genetic changes underlying such traits can be investigated in systems where sex-specific signaling and perception have emerged recently and show evidence of potential coevolution. A promising model is found in Drosophila prolongata, which exhibits a species-specific increase in the number of male chemosensory bristles. This transition is shown to coincides with recent evolutionary changes in cuticular hydrocarbon (CHC) profiles. Long-chain CHCs that are sexually monomorphic in the closest relatives of D. prolongata (D. rhopaloa, D. carrolli, D. kurseongensis, and D. fuyamai) are strongly male-biased in this species. An intraspecific female-limited polymorphism, where some females have male-like CHC profiles, was also identifid. Both the origin of sexually dimorphic CHC profiles and the female-limited polymorphism in D. prolongata involve changes in the relative amounts of three mono-alkene homologs, 9-tricosene, 9-pentacosene, and 9-heptacosene, all of which share a common biosynthetic origin and point to a potentially simple genetic change underlying these traits. These results suggest that pheromone synthesis may have coevolved with chemosensory perception and open the way for reconstructing the origin of sexual dimorphism in this communication system (Luo, 2019).

    Sexual Selection Does Not Increase the Rate of Compensatory Adaptation to a Mutation Influencing a Secondary Sexual Trait in Drosophila melanogaster

    Theoretical work predicts that sexual selection can enhance natural selection, increasing the rate of adaptation to new environments and helping purge harmful mutations. While some experiments support these predictions, remarkably little work has addressed the role of sexual selection on compensatory adaptation-populations' ability to compensate for the costs of deleterious alleles that are already present. This study tested whether sexual selection, as well as the degree of standing genetic variation, affect the rate of compensatory evolution via phenotypic suppression in experimental populations of Drosophila melanogaster. These populations were fixed for a spontaneous mutation causing mild abnormalities in the male sex comb, a structure important for mating success.This mutation was mapped to an ~85 kb region on the X chromosome containing three candidate genes, showed that the mutation is deleterious, and that its phenotypic expression and penetrance vary by genetic background. Experimental evolution was then performed, including a treatment where opportunity for mate choice was limited by experimentally enforced monogamy. Although evolved populations did show some phenotypic suppression of the morphological abnormalities in the sex comb, the amount of suppression did not depend on the opportunity for sexual selection. Sexual selection, therefore, may not always enhance natural selection; instead, the interaction between these two forces may depend on additional factors (Chandler, 2020).

    Co-evolving wing spots and mating displays are genetically separable traits in Drosophila

    The evolution of sexual traits often involves correlated changes in morphology and behavior. For example, in Drosophila, divergent mating displays are often accompanied by divergent pigment patterns. To better understand how such traits co-evolve, this study investigated the genetic basis of correlated divergence in wing pigmentation and mating display between the sibling species Drosophila elegans and Drosophila gunungcola. Drosophila elegans males have an area of black pigment on their wings known as a wing spot and appear to display this spot to females by extending their wings laterally during courtship. By contrast, D. gunungcola lost both of these traits. Using Multiplexed Shotgun Genotyping (MSG), an ~440 kb region on the X chromosome was identified that behaves like a genetic switch controlling the presence or absence of male-specific wing spots. This region includes the candidate gene optomotor-blind (omb), which plays a critical role in patterning the Drosophila wing. The genetic basis of divergent wing display is more complex, with at least two loci on the X chromosome and two loci on autosomes contributing to its evolution. Introgressing the X-linked region affecting wing spot development from D. gunungcola into D. elegans reduced pigmentation in the wing spots but did not affect the wing display, indicating that these are genetically separable traits. Consistent with this observation, broader sampling of wild D. gunungcola populations confirmed that the wing spot and wing display are evolving independently: some D. gunungcola males performed wing displays similar to D. elegans despite lacking wing spots. These data suggest that correlated selection pressures rather than physical linkage or pleiotropy are responsible for the coevolution of these morphological and behavioral traits. They also suggest that the change in morphology evolved prior to the change in behavior (Massey, 2020).

    Feminization of complex traits in Drosophila melanogaster via female-limited X chromosome evolution

    A handful of studies have investigated sexually antagonistic constraints on achieving sex-specific fitness optima, although exclusively through male-genome-limited evolution experiments. This article has established a female-limited X chromosome evolution experiment, where an X chromosome balancer was used to enforce the inheritance of the X through the matriline, thus removing exposure to male selective constraints. This approach eliminates the effects of sexually antagonistic selection on the X chromosome, permitting evolution toward a single sex-specific optimum. After multiple generations of selection, strong evidence was found that body size and development time had moved toward a female-specific optimum, whereas reproductive fitness and locomotion activity remained unchanged. The changes in body size and development time are consistent with previous results, and suggest that the X chromosome is enriched for sexually antagonistic genetic variation controlling these particular traits. The lack of change in reproductive fitness and locomotion activity could be due to a number of mutually nonexclusive explanations, including a lack of sexually antagonistic variance on the X chromosome for those traits or confounding effects of the use of the balancer chromosome. This study is the first to employ female-genome-limited selection and adds to the understanding of the complexity of sexually antagonistic genetic variation (Lund-Hansen, 2020)

    Positive genetic covariance between male sexual ornamentation and fertilizing capacity

    Postcopulatory sexual selection results from variation in competitive fertilization success among males and comprises powerful evolutionary forces that operate after the onset of mating. Theoretical advances in the field of sexual selection addressing the buildup and coevolutionary consequences of genetic coupling motivate the hypothesis that indirect postcopulatory sexual selection may promote evolution of male secondary sexual traits-those traits traditionally ascribed to mate choice and male fighting. A crucial prediction of this hypothesis is genetic covariance between trait expression and competitive fertilization success, which has been predicted to arise, for example, when traits subject to pre- and postcopulatory sexual selection are under positive correlational selection. This study imposed bidirectional artificial selection on male ornament (sex comb) size in Drosophila bipectinata and demonstrated increased competitive fertilization success as a correlated evolutionary response to increasing ornament size. Transcriptional analyses revealed that levels of specific seminal fluid proteins repeatedly shifted in response to this selection, suggesting that properties of the ejaculate, rather than the enlarged sex comb itself, contributed fertilizing capacity. Ultraprecise laser surgery was used to reduce ornament size of high-line males and found that their fertilizing superiority persisted despite the size reduction, reinforcing the transcriptional results. The data support the existence of positive genetic covariance between a male secondary sexual trait and competitive fertilization success, and suggest the possibility that indirect postcopulatory sexual selection may, under certain conditions, magnify net selection on ornamental trait expression (Polak, 2021).

    Nonadaptive molecular evolution of seminal fluid proteins in Drosophila

    Seminal fluid proteins (SFPs) are a group of reproductive proteins that are among the most evolutionarily divergent known. As SFPs can impact male and female fitness, these proteins have been proposed to evolve under postcopulatory sexual selection (PCSS). However, the fast change of the SFPs can also result from nonadaptive evolution, and the extent to which selective constraints prevent SFPs rapid evolution remains unknown. Using intra- and interspecific sequence information, along with genomics and functional data, this study examine the molecular evolution of approximately 300 SFPs in Drosophila. It was found that 50-57% of the SFP genes, depending on the population examined, are evolving under relaxed selection. Only 7-12% showed evidence of positive selection, with no evidence supporting other forms of PCSS, and 35-37% of the SFP genes were selectively constrained. Further, despite associations of positive selection with gene location on the X chromosome and protease activity, the analysis of additional genomic and functional features revealed their lack of influence on SFPs evolving under positive selection. These results highlight a lack of sufficient evidence to claim that most SFPs are driven to evolve rapidly by PCSS while identifying genomic and functional attributes that influence different modes of SFPs evolution (Patlar, 2021).

    Integrating genomics and multivariate evolutionary quantitative genetics: a case study of constraints on sexual selection in Drosophila serrata

    In evolutionary quantitative genetics, the genetic variance-covariance matrix, G, and the vector of directional selection gradients, β, are key parameters for predicting multivariate selection responses and genetic constraints. Historically, investigations of G and β have not overlapped with those dissecting the genetic basis of quantitative traits. Thus, it remains unknown whether these parameters reflect pleiotropic effects at individual loci. This study integrates multivariate genome-wide association study (GWAS) with G and β estimation in a well-studied system of multivariate constraint: sexual selection on male cuticular hydrocarbons (CHCs) in Drosophila serrata. In a panel of wild-derived re-sequenced lines, this study augments genome-based restricted maximum likelihood to estimate G alongside multivariate single nucleotide polymorphism (SNP) effects, detecting 532 significant associations from 1 652 276 SNPs. Constraint was evident, with β lying in a direction of G with low evolvability. Interestingly, minor frequency alleles typically increased male CHC-attractiveness suggesting opposing natural selection on β. SNP effects were significantly misaligned with the major eigenvector of G, gmax, but well aligned to the second and third eigenvectors g2 and g3. Potential factors leading to these varied results including multivariate stabilizing selection and mutational bias. This framework may be useful as researchers increasingly access genomic methods to study multivariate selection responses in wild populations (Reddiex, 2021).

    The importance of pre- and postcopulatory sexual selection promoting adaptation to increasing temperatures

    Global temperatures are increasing rapidly affecting species globally. Understanding if and how different species can adapt fast enough to keep up with increasing temperatures is of vital importance. One mechanism that can accelerate adaptation and promote evolutionary rescue is sexual selection. Two different mechanisms by which sexual selection can facilitate adaptation are pre- and postcopulatory sexual selection. However, the relative effects of these different forms of sexual selection in promoting adaptation are unknown. This study presents the results from an experimental study in which fruit flies Drosophila melanogaster were exposed to either no mate choice or 1 of 2 different sexual selection regimes (pre- and postcopulatory sexual selection) for 6 generations, under different thermal regimes. Populations showed evidence of thermal adaptation under precopulatory sexual selection, but this effect was not detected in the postcopulatory sexual selection and the no choice mating regime. This study further demonstrates that sexual dimorphism decreased when flies evolved under increasing temperatures, consistent with recent theory predicting more sexually concordant selection under environmental stress. These results suggest an important role for precopulatory sexual selection in promoting thermal adaptation and evolutionary rescue (Gomez-Llano, 2021).

    Sperm Cyst "Looping": A Developmental Novelty Enabling Extreme Male Ornament Evolution

    Postcopulatory sexual selection is credited as a principal force behind the rapid evolution of reproductive characters, often generating a pattern of correlated evolution between interacting, sex-specific traits. Because the female reproductive tract is the selective environment for sperm, one taxonomically widespread example of this pattern is the co-diversification of sperm length and female sperm-storage organ dimension. In Drosophila, having testes that are longer than the sperm they manufacture was believed to be a universal physiological constraint. Further, the energetic and time costs of developing long testes have been credited with underlying the steep evolutionary allometry of sperm length and constraining sperm length evolution in Drosophila. This report on the discovery of a novel spermatogenic mechanism-sperm cyst looping-that enables males to produce relatively long sperm in short testis. This phenomenon (restricted to members of the saltans and willistoni species groups) begins early during spermatogenesis and is potentially attributable to heterochronic evolution, resulting in growth asynchrony between spermatid tails and the surrounding spermatid and somatic cyst cell membranes. By removing the allometric constraint on sperm length, this evolutionary innovation appears to have enabled males to evolve extremely long sperm for their body mass while evading delays in reproductive maturation time. On the other hand, sperm cyst looping was found to exact a cost by requiring greater total energetic investment in testes and a pronounced reduction in male lifespan. The ecological selection pressures underlying the evolutionary origin and maintenance of this unique adaptation are discussed (Syed, 2021).

    Sperm metabolic rate predicts female mating frequency across Drosophila species

    Female mating rates vary widely, even among closely related species, but the reasons for this variation are not fully understood. Across Drosophila species, female mating frequencies are positively associated with sperm length. This association may be due in part to sperm limitation, with longer-spermed species transferring fewer sperm, or to cryptic female choice. However, a previously overlooked factor is sperm metabolic rate, which may correlate with sperm length. If faster-metabolizing sperm accumulate age-related cellular damage more quickly, then females should remate sooner to obtain fresh sperm. Alternatively, frequent female mating may select for increased sperm competitiveness via increased metabolism. This study measured sperm metabolism across 13 Drosophila species and compared these measures to published data on female mating rate and on sperm length. Using fluorescent lifetime imaging microscopy, this study quantified NAD(P)H metabolism ex vivo, in intact organs. Phylogenetically controlled regression reveals that sperm metabolic rate is positively associated with sperm length and with female mating frequency. Path analysis shows sperm length driving sperm metabolism and sperm metabolism either driving or being driven by female mating rate. While the causal directionality of these relationships remains to be fully resolved, and the effect of sperm metabolism on sperm aging and/or sperm competitiveness remains to be established, these results demonstrate the importance of sperm metabolism in sexual selection (Turnell, 2022).

    Experimental evolution reveals sex-specific dominance for surviving bacterial infection in laboratory populations of Drosophila melanogaster

    Males and females are subjected to distinct kinds of selection pressures, often leading to the evolution of sex-specific genetic architecture, an example being sex-specific dominance. Sex-specific dominance reversals (SSDRs), where alleles at sexually antagonistic loci are at least partially dominant in the sex they benefit, have been documented in Atlantic salmon, rainbow trout, and seed beetles. Another interesting feature of many sexually reproducing organisms is the asymmetric inheritance pattern of X chromosomes, which often leads to distinct evolutionary outcomes on X chromosomes compared to autosomes. Immunocompetence is a trait that has been extensively investigated for sexual dimorphism with growing evidence for sex-specific or sexually antagonistic variation. X chromosomes have been shown to harbor substantial immunity-related genetic variation in the fruit fly, Drosophila melanogaster. Using interpopulation crosses and cytogenetic cloning, this study investigated sex-specific dominance and the role of the X chromosome in improved postinfection survivorship of laboratory populations of D. melanogaster selected against pathogenic challenge by Pseudomonas entomophila. No contribution was detected of the X chromosome to the evolved immunocompetence of the selected populations, as well as to within-population variation in immunocompetence. However, strong evidence was found of sex-specific dominance related to surviving bacterial infection. These results indicate that alleles that confer a survival advantage to the selected populations are, on average, partially dominant in females but partially recessive in males. This could also imply an SSDR for overall fitness, given the putative evidence for sexually antagonistic selection affecting immunocompetence in Drosophila melanogaster. This study also highlighted sex-specific dominance as a potential mechanism of sex differences in immunocompetence, with population-level sex differences primarily driven by sex differences in heterozygotes (Arun, 2021).

    Evolutionary history of sexual selection affects microRNA profiles in Drosophila sperm Evolution

    The presence of small RNAs in sperm is a relatively recent discovery and little is currently known about their importance and functions. Environmental changes including social conditions and dietary manipulations are known to affect the composition and expression of some small RNAs in sperm and may elicit a physiological stress response resulting in an associated change in gamete miRNA profiles. This study tested how microRNA profiles in sperm are affected by variation in both sexual selection and dietary regimes in Drosophila melanogaster selection lines. The selection lines were exposed to standard versus low yeast diet treatments and three different population sex ratios (male-biased, female-biased, or equal sex) in a full-factorial design. After 38 generations of selection, all males were maintained on their selected diet and in a common garden male-only environment prior to sperm sampling. Transcriptome analyses were performed on miRNAs in purified sperm samples. 11 differentially expressed miRNAs were found with the majority showing differences between male- and female-biased lines. Dietary treatment only had a significant effect on miRNA expression levels in interaction with sex ratio. These findings suggest that long-term adaptation may affect miRNA profiles in sperm and that these may show varied interactions with short-term environmental changes (Hotzy, 2021).

    Sexual selection can partly explain low frequencies of Segregation Distorter alleles

    The Segregation Distorter (SD) allele found in Drosophila melanogaster distorts Mendelian inheritance in heterozygous males by causing developmental failure of non-SD spermatids, such that greater than 90% of the surviving sperm carry SD. This within-individual advantage should cause SD to fix, and yet SD is typically rare in wild populations. this study explores whether this paradox can be resolved by sexual selection, by testing if males carrying three different variants of SD suffer reduced pre- or post-copulatory reproductive success. This study finds that males carrying the SD allele are just as successful at securing matings as control males, but that one SD variant (SD-5) reduces sperm competitive ability and increases the likelihood of female remating. The results inform a theoretical model; It was discovered that sexual selection could limit SD to natural frequencies when sperm competitive ability and female remating rate equalled the values observed for SD-5. However, sexual selection was unable to explain natural frequencies of the SD allele when the model was parameterized with the values found for two other SD variants, indicating that sexual selection alone is unlikely to explain the rarity of SD (Keaney, 2021).

    Repeated evidence that the accelerated evolution of sperm is associated with their fertilization function

    Spermatozoa are the most morphologically diverse cell type, leading to the widespread assumption that they evolve rapidly. However, there is no direct evidence that sperm evolve faster than other male traits. Such a test requires comparing male traits that operate in the same selective environment, ideally produced from the same tissue, yet vary in function. This study examined rates of phenotypic evolution in sperm morphology using two insect groups where males produce fertile and non-fertile sperm types (Drosophila species from the obscura group and a subset of Lepidoptera species), where these constraints are solved. Moreover, in Drosophila, the relationship between rates of sperm evolution and the link with the putative selective pressures of fertilization function and postcopulatory sexual selection exerted by female reproductive organs were tested. Repeated evolutionary patterns were found across these insect groups-lengths of fertile sperm evolve faster than non-fertile sperm. In Drosophila, fertile sperm length evolved faster than body size, but at the same rate as female reproductive organ length. Rates of evolution of different sperm components were also compared, showing that head length evolves faster in fertile sperm while flagellum length evolves faster in non-fertile sperm. This study provides direct evidence that sperm length evolves more rapidly in fertile sperm, probably because of their functional role in securing male fertility and in response to selection imposed by female reproductive organs (Fitzpatrick, 2020).

    Divergence of responses to variable socio-sexual environments in laboratory populations of Drosophila melanogaster evolving under altered operational sex ratios

    Post-copulatory sexual selection (PSS) is an important selective force that determines fitness in polyandrous species. PSS can be intense in some cases and can drive the evolution of remarkable ejaculate properties. In males, investment in ejaculate plays an important role in the outcome of PSS. Thus, males are expected to adaptively tailor their ejaculate according to the perceived competition in their vicinity. Plastic responses in ejaculate investment to variation in intrasexual competition are disparate and widespread in males. This study investigated the evolution of plasticity in reproductive traits using Drosophila melanogaster populations evolving for more than 150 generations under male- or female-biased sex ratios. When exposed to different numbers of competitors early in their life, males from these two regimes responded differently in terms of their copulation duration and sperm competitive ability. In addition, the effect of this early life experience wore off at different rates in males of male-biased and female-biased regimes with increasing time from the removal of competitive cues. Furthermore, this study finds that males change their reproductive strategies depending upon the identity of rival males. Together, these results provide evidence of the evolution of male reproductive investment that depends on socio-sexual cues experienced early in life (Maggu, 2020).

    The Drosophila seminal proteome and its role in postcopulatory sexual selection

    Postcopulatory sexual selection (PCSS), comprised of sperm competition and cryptic female choice, has emerged as a widespread evolutionary force among polyandrous animals. There is abundant evidence that PCSS can shape the evolution of sperm. However, sperm are not the whole story: they are accompanied by seminal fluid substances that play many roles, including influencing PCSS. Foremost among seminal fluid models is Drosophila melanogaster, which displays ubiquitous polyandry, and exhibits intraspecific variation in a number of seminal fluid proteins (Sfps) that appear to modulate paternity share. This study first consolidated current information on the identities of D. melanogaster Sfps. Comparing between D. melanogaster and human seminal proteomes, evidence is found of similarities between many protein classes and individual proteins, including some D. melanogaster Sfp genes linked to PCSS, suggesting evolutionary conservation of broad-scale functions. Experimental evidence for the functions of D. melanogaster Sfps in PCSS and sexual conflict is reviewed. Gaps are identified in current knowledge and areas for future research, including an enhanced identification of PCSS-related Sfps, their interactions with rival sperm and with females, the role of qualitative changes in Sfps and mechanisms of ejaculate tailoring. This article is part of the theme issue 'Fifty years of sperm competition' (Wigby, 2020).

    Female-limited X-chromosome evolution effects on male pre- and post-copulatory success

    Intralocus sexual conflict arises when the expression of shared alleles at a single locus generates opposite fitness effects in each sex (i.e. sexually antagonistic alleles), preventing each sex from reaching its sex-specific optimum. Despite its importance to reproductive success, the relative contribution of intralocus sexual conflict to male pre- and post-copulatory success is not well-understood. This study used a female-limited X-chromosome (FLX) evolution experiment in Drosophila melanogaster to limit the inheritance of the X-chromosome to the matriline, eliminating possible counter-selection in males and allowing the X-chromosome to accumulate female-benefit alleles. After more than 100 generations of FLX evolution, the effect of the evolved X-chromosome on male attractiveness and sperm competitiveness was studied. A non-significant increase was found in attractiveness and decrease was found in sperm offence ability in males expressing the evolved X-chromosomes, but a significant increase in their ability to avoid displacement by other males' sperm. This is consistent with a trade-off between these traits, perhaps mediated by differences in body size, causing a small net reduction in overall male fitness in the FLX lines. These results indicate that the X-chromosome in D. melanogaster is subject to selection via intralocus sexual conflict in males (Manat, 2021).

    Sexually antagonistic coevolution between the sex chromosomes of Drosophila melanogaster

    Antagonistic interactions between the sexes are important drivers of evolutionary divergence. Interlocus sexual conflict is generally described as a conflict between alleles at two interacting loci whose identity and genomic location are arbitrary, but with opposite fitness effects in each sex. This study builds on previous theory by suggesting that when loci under interlocus sexual conflict are located on the sex chromosomes it can lead to cycles of antagonistic coevolution between them and therefore between the sexes. This hypothesis was tested by performing experimental crosses using Drosophila melanogaster where the sex chromosomes was reciprocally exchanged between five allopatric wild-type populations in a round-robin design. Disrupting putatively coevolved sex chromosome pairs resulted in increased male reproductive success in 16 of 20 experimental populations (10 of which were individually significant), but also resulted in lower offspring egg-to-adult viability that affected both male and female fitness. After 25 generations of experimental evolution these sexually antagonistic fitness effects appeared to be resolved. To formalize the hypothesis, population genetic models were developed of antagonistic coevolution using fitness expressions based on the empirical results. The model predictions support the conclusion that antagonistic coevolution between the sex chromosomes is plausible under the fitness effects observed in these experiments. Together, these results lend both empirical and theoretical support to the idea that cycles of antagonistic coevolution can occur between sex chromosomes and illustrate how this process, in combination with autosomal coadaptation, may drive genetic and phenotypic divergence between populations (Lund-Hansen, 2021).

    Individual and synergistic effects of male external genital traits in sexual selection

    Male genital traits exhibit extraordinary interspecific phenotypic variation. This remarkable and general evolutionary trend is widely considered to be the result of sexual selection. However, a good understanding of whether or how individual genital traits function in different competitive arenas (episodes of sexual selection), or how different genital traits may interact to influence competitive outcomes, is still not available. This study used an experimental approach based on high-precision laser phenotypic engineering to address these outstanding questions, focusing on three distinct sets of micron-scale external (nonintromittent) genital spines in male Drosophila kikkawai Burla (Diptera: Drosophilidae). Elimination of the large pair of spines on the male secondary claspers sharply reduced male ability to copulate, yet elimination of the other sets of spines on the primary and secondary claspers had no significant effects on copulation probability. Intriguingly, both the large spines on the secondary claspers and the cluster of spines on the primary claspers were found to independently promote male competitive fertilization success. Moreover, when large and small secondary clasper spines were simultaneously shortened in individual males, these males suffered greater reductions in fertilization success relative to males whose traits were altered individually, providing evidence for synergistic effects of external genital traits on fertilization success. Overall, the results are significant in demonstrating that a given genital trait (the large spines on the secondary claspers) can function in different episodes of sexual selection, and distinct genital traits may interact in sexual selection. The results offer an important contribution to evolutionary biology by demonstrating an understudied selective mechanism, operating via subtle trait interactions in a post-insemination context, by which genital traits may be co-evolving (Rodriguez-Exposito, 2019).

    Phylogenomic Insights into the Evolution of Stinging Wasps and the Origins of Ants and Bees

    The stinging wasps (Hymenoptera: Aculeata) are an extremely diverse lineage of hymenopteran insects, encompassing over 70,000 described species and a diversity of life history traits, including ectoparasitism, cleptoparasitism, predation, pollen feeding (bees [Anthophila] and Masarinae), and eusociality (social vespid wasps, ants, and some bees). The most well-studied lineages of Aculeata are the ants, which are ecologically dominant in most terrestrial ecosystems, and the bees, the most important lineage of angiosperm-pollinating insects. Establishing the phylogenetic affinities of ants and bees helps in understanding and reconstruction of patterns of social evolution as well as leading to full appreciation of the biological implications of the switch from carnivory to pollen feeding (pollenivory). Despite recent advancements in aculeate phylogeny, considerable uncertainty remains regarding higher-level relationships within Aculeata, including the phylogenetic affinities of ants and bees. Ultraconserved element (UCE) phylogenomics was used to resolve relationships among stinging-wasp families, gathering sequence data from >800 UCE loci and 187 samples, including 30 out of 31 aculeate families. The 187-taxon dataset was analyzed using multiple analytical approaches, and several alternative taxon sets were analyzed. Alternative hypotheses for the phylogenetic positions of ants and bees were tested. The results present a highly supported phylogeny of the stinging wasps. Most importantly, it was found unequivocal evidence that ants are the sister group to bees+apoid wasps (Apoidea) and that bees are nested within a paraphyletic Crabronidae. It was also demonstrated that taxon choice can fundamentally impact tree topology and clade support in phylogenomic inference (Branstetter, 2017).

    Interactions between the developmental and adult social environments mediate group dynamics and offspring traits in Drosophila melanogaster

    Developmental conditions can strongly influence adult phenotypes and social interactions, which in turn affect key evolutionary processes such as sexual selection and sexual conflict. While the implications of social interactions in phenotypically mixed populations at the individual level are increasingly well known, how these effects influence the fate of groups remains poorly understood, which limits understanding of the broader ecological implications. To address this problem this study manipulated adult phenotypes and social composition in Drosophila melanogaster - by experimentally manipulating the larval density of the group-members - and measured a range of group-level outcomes across the lifespan of groups. Adult groups composed of exclusively low larval-density individuals showed high courtship levels, and low early reproductive rates, group growth rates, offspring mass and offspring eclosion success, relative to high larval-density or mixed larval-density groups. Furthermore, high larval-density groups had lower survival. Offspring mass increased with time, but at a reduced rate in groups when male group members (but not females) were from a mixture of larval-densities; peak reproductive rates were also earlier in these groups. These results suggest that that variation in developmental conditions experienced by adult group members can modify the reproductive output of groups (Morimoto, 2017).

    Genomic regions influencing aggressive behavior in honey bees are defined by colony allele frequencies

    For social animals, the genotypes of group members affect the social environment, and thus individual behavior, often indirectly. This study used genome-wide association studies (GWAS) to determine the influence of individual vs. group genotypes on aggression in honey bees. Aggression in honey bees arises from the coordinated actions of colony members, primarily nonreproductive "soldier" bees, and thus, experiences evolutionary selection at the colony level. This study shows that individual behavior is influenced by colony environment, which in turn, is shaped by allele frequency within colonies. Using a population with a range of aggression, individual whole genomes were sequenced and for genotype-behavior associations were looked for within colonies in a common environment. There were no significant correlations between individual aggression and specific alleles. By contrast, strong correlations were found between colony aggression and the frequencies of specific alleles within colonies, despite a small number of colonies. Associations at the colony level were highly significant and were very similar among both soldiers and foragers, but they covaried with one another. One strongly significant association peak, containing an ortholog of the Drosophila sensory gene dpr4 (see Dips and Dprs) on linkage group (chromosome) 7, showed strong signals of both selection and admixture during the evolution of gentleness in a honey bee population. Links were thus found between colony genetics and group behavior and also, molecular evidence was found for group-level selection, acting at the colony level. It is concluded that group genetics dominates individual genetics in determining the fatal decision of honey bees to sting (Avalos, 2020).

    Population differences in olfaction accompany host shift in Drosophila mojavensis
    Evolutionary shifts in plant-herbivore interactions provide a model for understanding the link among the evolution of behaviour, ecological specialization and incipient speciation. Drosophila mojavensis uses different host cacti across its range, and volatile chemicals emitted by the host are the primary cue for host plant identification. This study shows that changes in host plant use between distinct D. mojavensis populations are accompanied by changes in the olfactory system. Specifically, differences were observed in olfactory receptor neuron specificity and sensitivity, as well as changes in sensillar subtype abundance, between populations. Additionally, RNA-seq analyses reveal differential gene expression between populations for members of the odorant receptor gene family. Hence, alterations in host preference are associated with changes in development, regulation and function at the olfactory periphery (Crowley-Gall, 2016).

    Shedding light on the grey zone of speciation along a continuum of genomic divergence

    Speciation results from the progressive accumulation of mutations that decrease the probability of mating between parental populations or reduce the fitness of hybrids-the so-called species barriers. Of primary importance is the prevalence of gene flow between diverging entities, which is central in most species concepts and has been widely discussed in recent years. This study explored the continuum of speciation thanks to a comparative analysis of genomic data from 61 pairs of populations/species of animals with variable levels of divergence. The intermediate "grey zone" of speciation, in which taxonomy is often controversial, spans from 0.5% to 2% of net synonymous Divergence, irrespective of species life history traits or ecology. Thanks to appropriate modeling of among-locus variation in genetic drift and introgression rate, this study clarifies the status of the majority of ambiguous cases and uncovers a number of cryptic species. This analysis also reveals the high incidence in animals of semi-isolated species (when some but not all loci are affected by barriers to gene flow) and highlights the intrinsic difficulty, both statistical and conceptual, of delineating species in the grey zone of speciation (Roux, 2016).

    Genetic differentiation and adaptive evolution at reproductive loci in incipient Drosophila species

    Accessory gland proteins (Acps; see Drosophila Sex Peptide and 0vulin) are part of the seminal fluid of male Drosophila flies. Some Acps have exceptionally high evolutionary rates and evolve under positive selection. Proper interactions between Acps and female reproductive molecules are essential for fertilization. These observations lead to suggestions that fast evolving Acps could be involved in speciation by promoting reproductive incompatibilities between emerging species. To test this hypothesis, population genetics data were used for three sibling species: D. mayaguana, D. parisiena, and D. straubae. The latter two species are morphologically very similar and show only incipient reproductive isolation. This system allowed examination of Acp evolution at different time frames in respect to speciation and reproductive isolation. Comparing data of 14 Acp loci with data obtained for other genomic regions, it was found that some Acps show extraordinarily high levels of divergence between D. mayaguana and its two sister species D. parisiena, and D. straubae. This divergence was likely driven by adaptive evolution at several loci. No fixed nucleotide differences were found between D. parisiena and D. straubae, however. Nevertheless, some Acp loci did show significant differentiation between these species associated with signs of positive selection; these loci may be involved in this early phase of the speciation process (Almeida, 2016).

    Early events in speciation: Cryptic species of Drosophila aldrichi

    Understanding the earliest events in speciation remains a major challenge in evolutionary biology. Thus identifying species whose populations are beginning to diverge can provide useful systems to study the process of speciation. Drosophila aldrichi, a cactophilic fruit fly species with a broad distribution in North America, has long been assumed to be a single species owing to its morphological uniformity. While previous reports either of genetic divergence or reproductive isolation among different D. aldrichi strains have hinted at the existence of cryptic species, the evolutionary relationships of this species across its range have not been thoroughly investigated. This study shows that D. aldrichi actually is paraphyletic with respect to its closest relative, Drosophila wheeleri, and that divergent D. aldrichi lineages show complete hybrid male sterility when crossed. The data support the interpretation that there are at least two species of D. aldrichi, making these flies particularly attractive for studies of speciation in an ecological and geographical context (Castro Vargas, 2017).

    Genetic divergence and the number of hybridizing species affect the path to homoploid hybrid speciation

    Hybridization is often maladaptive and in some instances has led to the loss of biodiversity. However, hybridization can also promote speciation, such as during homoploid hybrid speciation, thereby generating biodiversity. Despite examples of homoploid hybrid species, the importance of hybridization as a speciation mechanism is still widely debated, and a general understanding is lacking of the conditions most likely to generate homoploid hybrid species. This study shows that the level of genetic divergence between hybridizing species has a large effect on the probability that their hybrids evolve reproductive isolation. Populations of hybrids formed by parental species with intermediate levels of divergence were more likely to mate assortatively, and discriminate against their parental species, than those generated from weakly or strongly diverged parental species. Reproductive isolation was also found between hybrid populations, suggesting differential sorting of parental traits across populations. Finally, hybrid populations derived from three species were more likely to evolve reproductive isolation than those derived from two species, supporting arguments that hybridization-supplied genetic diversity can lead to the evolution of novel "adaptive systems" and promote speciation. These results illustrate when hybridization and admixture is expected to promote hybrid speciation. Whether homoploid hybrid speciation is a common speciation mechanism in general remains an outstanding empirical question (Comeault, 2018).

    Tissue-specific cis-regulatory divergence implicates eloF in inhibiting interspecies mating in Drosophila

    Reproductive isolation is a key component of speciation. In many insects, a major driver of this isolation is cuticular hydrocarbon pheromones, which help to identify potential intraspecific mates. When the distributions of related species overlap, there may be strong selection on mate choice for intraspecific partners because interspecific hybridization carries significant fitness costs. Drosophila has been a key model for the investigation of reproductive isolation; although both male and female mate choices have been extensively investigated, the genes underlying species recognition remain largely unknown. To explore the molecular mechanisms underlying Drosophila speciation, tissue-specific cis-regulatory divergence was identifed using RNA sequencing (RNA-seq) in D. simulans x D. sechellia hybrids. By focusing on cis-regulatory changes specific to female oenocytes, the tissue that produces cuticular hydrocarbons, this study identified a small number of candidate genes were identified. One of these, the fatty acid elongase eloF, broadly affects the hydrocarbons present on D. sechellia and D. melanogaster females, as well as the propensity of D. simulans males to mate with them. Therefore, cis-regulatory changes in eloF may be a major driver in the sexual isolation of D. simulans from multiple other species. The RNA-seq approach proved to be far more efficient than quantitative trait locus (QTL) mapping in identifying candidate genes; the same framework can be used to pinpoint candidate drivers of cis-regulatory divergence in traits differing between any interfertile species (Combs, 2018).

    Gene flow mediates the role of sex chromosome meiotic drive during complex speciation

    During speciation, sex chromosomes often accumulate interspecific genetic incompatibilities faster than the rest of the genome. The drive theory posits that sex chromosomes are susceptible to recurrent bouts of meiotic drive and suppression, causing the evolutionary build-up of divergent cryptic sex-linked drive systems and, incidentally, genetic incompatibilities. To assess the role of drive during speciation, this study combined high-resolution genetic mapping of X-linked hybrid male sterility with population genomics analyses of divergence and recent gene flow between the fruitfly species, Drosophila mauritiana and D. simulans. The findings reveal a high density of genetic incompatibilities and a corresponding dearth of gene flow on the X chromosome. Surprisingly, a known drive element recently migrated between species and, rather than contributing to interspecific divergence, caused a strong reduction in local sequence divergence, undermining the evolution of hybrid sterility. Gene flow can therefore mediate the effects of selfish genetic elements during speciation (Meiklejohn, 2018).

    Aggression and courtship differences found in Drosophila melanogaster from two different microclimates at Evolution Canyon, Israel

    Aggression and courtship behavior were examined of wild Drosophila melanogaster flies isolated from two contrasting microclimates found at Evolution Canyon in Mt. Carmel, Israel: an African-like dry tropical Slope (AS) and a European-like humid temperate Slope (ES), separated by 250 meters. Intraslope aggression between same sex fly pairings collected from the same slope was measured and compared. Both male and female flies displayed similar fighting abilities from both slopes. ES males, however, from the humid biome, showed a tendency to lunge more per aggressive encounter, compared with AS males from the dry biome. Interslope aggression was tested by pairing flies from opposite slopes. ES males displayed higher numbers of lunges, and won more fights against their AS opponents. Enhanced courtship performances were observed in ES compared to AS males. The fighting and courtship superiority seen in ES males could reinforce fitness and pre-mating reproductive isolation mechanisms that underlie incipient sympatric speciation. This may support an evolutionary advantage of adaptively divergent fruit fly aggression phenotypes from different environments (Palavicino-Maggio, 2019).

    Experimental introgression to evaluate the impact of sex specific traits on Drosophila melanogaster incipient speciation

    Sex specific traits are involved in speciation but it is difficult to determine whether their variation initiates or reinforces sexual isolation. In some insects, speciation depends of the rapid change of expression in desaturase genes coding for sex pheromones. Two closely related desaturase genes are involved in Drosophila melanogaster pheromonal communication: desat1 affects both the production and the reception of sex pheromones while desat2 is involved in their production in flies of Zimbabwe populations. There is a strong asymmetric sexual isolation between Zimbabwe populations and all other "Cosmopolitan" populations: Zimbabwe females rarely copulate with Cosmopolitan males whereas Zimbabwe males readily copulate with all females. All populations express desat1 but only Zimbabwe strains show high desat2 expression. To evaluate the impact of sex pheromones, female receptivity and desat expression on the incipient speciation process between Zimbabwe and Cosmopolitan populations, the Zimbabwe genome was introgressed into a Cosmopolitan genome labeled with the white mutation, using a multi-generation procedure. The association between these sex-specific traits was determined during the procedure. The production of pheromones was largely dissociated between the sexes. The copulation frequency (but not latency) was highly correlated with the female-but not with the male-principal pheromones. Two stable white lines were finally obtained showing Zimbabwe-like sex pheromones, copulation discrimination and desat expression. This study indicates that the variation of sex pheromones and mating discrimination depend of distinct-yet overlapping-sets of genes in each sex suggesting that their cumulated effects participate to reinforce the speciation process (Cortot, 2019).

    The evolution of male and female mating preferences in Drosophila speciation

    The relative importance of male and female mating preferences in causing sexual isolation between species remains a major unresolved question in speciation. Despite previous work showing that male courtship bias and/or female copulation bias for conspecifics occur in many taxa, the present study is one of the first large-scale works to study their relative divergence. To achieve this, data from the literature and present experiments were used across 66 Drosophila species pairs. The results revealed that male and female mate preferences are both ubiquitous in Drosophila but evolved largely independently, suggesting different underlying evolutionary and genetic mechanisms. Moreover, their relative divergence strongly depended on the geographical relationship of species. Between allopatric species, male courtship and female copulation preferences diverged at very similar rates, evolving approximately linearly with time of divergence. In sharp contrast, between sympatric species pairs, female preferences diverged much more rapidly than male preferences and were the only drivers of enhanced sexual isolation in sympatry and Reproductive Character Displacement (RCD). Not only does this result suggest that females are primarily responsible for such processes as reinforcement, but it also implies that evolved female preferences may reduce selection for further divergence of male courtship preferences in sympatry (Yukilevich, 2019).

    Divergent selection on behavioural and chemical traits between reproductively isolated populations of Drosophila melanogaster

    Speciation is driven by traits that can act to prevent mating between nascent lineages, including male courtship and female preference for male traits. Mating barriers involving these traits evolve quickly because there is strong selection on males and females to maximize reproductive success, and the tight co-evolution of mating interactions can lead to rapid diversification of sexual behaviour. Populations of Drosophila melanogaster show strong asymmetrical reproductive isolation that is correlated with geographic origin. Using strains that capture natural variation in mating traits, two key questions were asked: which specific male traits are females selecting, and are these traits under divergent sexual selection? These questions have proven extremely challenging to answer, because even in closely related lineages males often differ in multiple traits related to mating behaviour. These questions were addressed by estimating selection gradients for male courtship and cuticular hydrocarbons for two different female genotypes. Specific behaviours and particular cuticular hydrocarbons were identified that are under divergent sexual selection and could potentially contribute to premating reproductive isolation. Additionally, it is reported that a subset of these traits are plastic; males adjust these traits based on the identity of the female genotype they interact with. These results suggest that even when male courtship is not fixed between lineages, ongoing selection can act on traits that are important for reproductive isolation (Jin, 2022).

    Divergence of a speciation trait through artificial selection: Insights into constraints, by-product effects and sexual isolation

    Speciation and a href="../aimain/7evolution2.htm#Isolation2">sexual isolation often occur when divergent female mating preferences target male secondary sexual traits. Despite the importance of such male signals, little is known about their evolvability and genetic linkage to other traits during speciation. To answer these questions, divergent artificial selection was imposed for 10 non-overlapping generations on the Inter-Pulse-Interval (IPI) of male courtship songs; which has been previously shown to be a major species recognition trait for females in the Drosophila athabasca species complex. Focusing on one of the species, Drosophila mahican (previously known as EA race), IPI's were examined: (1) rate of divergence, (2) response to selection in different directions, (3) genetic architecture of divergence and (4) by-product effects on other traits that have diverged in the species complex. Rapid and consistent response was found for for higher IPI but less response to lower IPI; implying asymmetrical constraints. Genetic divergence in IPI differed from natural species in X versus autosome contribution and in dominance, suggesting that evolution may take different paths. Finally, selection on IPI did not alter other components of male songs, or other ecological traits, and did not cause divergence in female preferences, as evidenced by lack of sexual isolation. This suggests that divergence of male courtship song IPI is unconstrained by genetic linkage with other traits in this system. This lack of linkage between male signals and other traits implies that female preferences or ecological selection can co-opt and mould specific male signals for species recognition free of genetic constraints from other traits (Yukilevich, 2023).

    Drosophila females have an acoustic preference for symmetric males

    Theoretically, symmetry in bilateral animals is subject to sexual selection, since it can serve as a proxy for genetic quality of competing mates during mate choice. This study reports female preference for symmetric males in Drosophila, using a mate-choice paradigm where males with environmentally or genetically induced wing asymmetry were competed. Analysis of courtship songs revealed that males with asymmetric wings produced songs with asymmetric features that served as acoustic cues, facilitating this female preference. Females experimentally evolved in the absence of mate choice lost this preference for symmetry, suggesting that it is maintained by sexual selection (Vijendravarma, 2022).

    Experimental sexual selection affects the evolution of physiological and life-history traits

    Sexual selection and sexual conflict are expected to affect all aspects of the phenotype, not only traits that are directly involved in reproduction. This study shows coordinated evolution of multiple physiological and life-history traits in response to long-term experimental manipulation of the mating system in populations of Drosophila pseudoobscura. Development time was extended under polyandry relative to monogamy in both sexes, potentially due to higher investment in traits linked to sexual selection and sexual conflict. Individuals (especially males) evolving under polyandry had higher metabolic rates and locomotor activity than those evolving under monogamy. Polyandry individuals also invested more in metabolites associated with increased endurance capacity and efficient energy metabolism and regulation, namely lipids and glycogen. Finally, polyandry males were less desiccation- and starvation resistant than monogamy males, suggesting trade-offs between resistance and sexually selected traits. These results provide experimental evidence that mating systems can impose selection that influences the evolution of non-sexual phenotypes such as development, activity, metabolism and nutrient homeostasis (Garlovsky, 2022).

    Natural variation at a single gene generates sexual antagonism across fitness components in Drosophila

    Mutations with conflicting fitness effects in males and females accumulate in sexual populations, reducing their adaptive capacity. Although quantitative genetic studies indicate that sexually antagonistic polymorphisms are common, their molecular basis and population genetic properties remain poorly understood. This study shows in fruit flies how natural variation at a single gene generates sexual antagonism through phenotypic effects on cuticular hydrocarbon (CHC) traits that function as both mate signals and protectors against abiotic stress across a latitudinal gradient. Tropical populations of Drosophila serrata have polymorphic CHCs producing sexual antagonism through opposing but sex-limited effects on these two fitness-related functions. This study dissected this polymorphism to a single fatty-acyl CoA reductase gene, DsFAR2-B, that is expressed in oenocyte cells where CHCs are synthesized. RNAi-mediated disruption of the DsFAR2-B ortholog in D. melanogaster oenocytes affected CHCs in a similar way to that seen in D. serrata. Population genomic analysis revealed that balancing selection likely operates at the DsFAR2-B locus in the wild. This study provides insights into the genetic basis of sexual antagonism in nature and connects sexually varying antagonistic selection on phenotypes with balancing selection on genotypes that maintains molecular variation (Rusuwa, 2022).

    Experimental sexual selection reveals rapid evolutionary divergence in sex-specific transcriptomes and their interactions following mating

    Post copulatory interactions between the sexes in internally fertilizing species elicits both sexual conflict and sexual selection. Macroevolutionary and comparative studies have linked these processes to rapid transcriptomic evolution in sex-specific tissues and substantial transcriptomic post mating responses in females, patterns of which are altered when mating between reproductively isolated species. This study tested multiple predictions arising from sexual selection and conflict theory about the evolution of sex-specific and tissue-specific gene expression and the post mating response at the microevolutionary level. Following over 150 generations of experimental evolution under either reduced (enforced monogamy) or elevated (polyandry) sexual selection in Drosophila pseudoobscura, this study found a substantial effect of sexual selection treatment on transcriptomic divergence in virgin male and female reproductive tissues (testes, male accessory glands, the female reproductive tract and ovaries). Sexual selection treatment also had a dominant effect on the post mating response, particularly in the female reproductive tract - the main arena for sexual conflict - compared to ovaries. This effect was asymmetric with monandry females typically showing more post mating responses than polyandry females, with enriched gene functions varying across treatments. The evolutionary history of the male partner had a larger effect on the post mating response of monandry females, but females from both sexual selection treatments showed unique patterns of gene expression and gene function when mating with males from the alternate treatment. These microevolutionary results mostly confirm comparative macroevolutionary predictions on the role of sexual selection on transcriptomic divergence and altered gene regulation arising from divergent coevolutionary trajectories between sexual selection treatments (Veltsos, 2022).

    Sexual selection and the evolution of condition-dependence: an experimental test at two resource levels

    Stronger condition-dependence in sexually-selected traits is well-documented, but how this relationship is established remains unknown. Moreover, resource availability can shape responses to sexual selection, but resource effects on the relationship between sexual selection and condition-dependence are also unknown. This study directly tested the hypotheses that sexual selection drives the evolution of stronger-condition-dependence and that resource availability affects the ouƒtcome, by evolving fruit flies (Drosophila melanogaster) under relatively strong or weak sexual selection (through varied sex ratios) and at resource-poor or resource-rich adult diets. Then condition was experimentally manipulated via developmental diet, and condition-dependence in adult morphology, behaviour and reproduction was assed. Stronger condition-dependence in female size was observed in male-biased populations and in female ovariole production in resource-limited populations. However, no evidence was found that male condition-dependence increased in response to sexual selection, or that responses depended on resource levels. These results offer no support for the hypotheses that sexual selection increases male condition-dependence or that sexual selection's influence on condition-dependence is influenced by resource availability. This study is the first experimental test of these hypotheses. If the results that are reported are general, then sexual selection's influence on the evolution of condition-dependence may be less important than predicted (Bath, 2023).

    Evolutionary conservation and diversification of auditory neural circuits that process courtship songs in Drosophila

    Acoustic communication signals diversify even on short evolutionary time scales. To understand how the auditory system underlying acoustic communication could evolve, this study conducted a systematic comparison of the early stages of the auditory neural circuit involved in song information processing between closely-related fruit-fly species. Male Drosophila melanogaster and D. simulans produce different sound signals during mating rituals, known as courtship songs. Female flies from these species selectively increase their receptivity when they hear songs with conspecific temporal patterns. This study firstly confirmed interspecific differences in temporal pattern preferences; D. simulans preferred pulse songs with longer intervals than D. melanogaster. Primary and secondary song-relay neurons, JO neurons and AMMC-B1 neurons, shared similar morphology and neurotransmitters between species. The temporal pattern preferences of AMMC-B1 neurons were also relatively similar between species, with slight but significant differences in their band-pass properties. Although the shift direction of the response property matched that of the behavior, these differences are not large enough to explain behavioral differences in song preferences. This study enhances understanding of the conservation and diversification of the architecture of the early-stage neural circuit which processes acoustic communication signals (Ohashi, 2023).

    Expansion and loss of sperm nuclear basic protein genes in Drosophila correspond with genetic conflicts between sex chromosomes

    Many animal species employ sperm nuclear basic proteins (SNBPs; see Protamine A) or protamines to package sperm genomes tightly. SNBPs vary across animal lineages and evolve rapidly in mammals. This study used a phylogenomic approach to investigate SNBP diversification in Drosophila species. It was found that most SNBP genes in Drosophila melanogaster evolve under positive selection except for genes essential for male fertility. Unexpectedly, evolutionarily young SNBP genes are more likely to be critical for fertility than ancient, conserved SNBP genes. For example, CG30056 is dispensable for male fertility despite being one of three SNBP genes universally retained in Drosophila species. Nineteen independent SNBP gene amplification events were found that occurred preferentially on sex chromosomes. Conversely, the montium group of Drosophila species lost otherwise-conserved SNBP genes, coincident with an X-Y chromosomal fusion. Furthermore, SNBP genes that became linked to sex chromosomes via chromosomal fusions were more likely to degenerate or relocate back to autosomes. It is hypothesized that autosomal SNBP genes suppress meiotic drive, whereas sex-chromosomal SNBP expansions lead to meiotic drive. X-Y fusions in the montium group render autosomal SNBPs dispensable by making X-versus-Y meiotic drive obsolete or costly. Thus, genetic conflicts between sex chromosomes may drive SNBP rapid evolution during spermatogenesis in Drosophila species (Chang, 2023).

    Selection and Geography Shape Male Reproductive Tract Transcriptomes in Drosophila Melanogaster

    Transcriptome analysis of several animal clades suggests that male reproductive tract gene expression evolves quickly. However, the factors influencing the abundance and distribution of within-species variation, the ultimate source of interspecific divergence, are poorly known. Drosophila melanogaster, an ancestrally African species that has recently spread throughout the world and colonized the Americas in the last roughly 100 years, exhibits phenotypic and genetic latitudinal clines on multiple continents, consistent with a role for spatially varying selection in shaping its biology. Nevertheless, geographic expression variation in the Americas is poorly described, as is its relationship to African expression variation. This study investigate these issues through analysis of two male reproductive tissue transcriptomes (testis and accessory gland) in samples from Maine (USA), Panama, and Zambia. Dramatic differences were found between these tissues in differential expression between Maine and Panama, with the accessory glands exhibiting abundant expression differentiation and the testis exhibiting very little. Latitudinal expression differentiation appears to be influenced by selection on Panama expression phenotypes. While the testis shows little latitudinal expression differentiation, it exhibits much greater differentiation than the accessory gland in Zambia vs. American population comparisons. Expression differentiation for both tissues is non-randomly distributed across the genome on a chromosome arm scale. Interspecific expression divergence between D. melanogaster and D. simulans is discordant with rates of differentiation between D. melanogaster populations. Strongly heterogeneous expression differentiation across tissues and timescales suggests a complex evolutionary process involving major temporal changes in the way selection influences expression evolution in these organs (Cridland, 2023).

    Phenotypic extremes or extreme phenotypes? On the use of large and small-bodied "phenocopied" Drosophila melanogaster males in studies of sexual selection and conflict

    In the fruit fly, Drosophila melanogaster, variation in body size is influenced by a number of different factors and may be strongly associated with individual condition, performance and success in reproductive competitions. Consequently, intra-sexual variation in size in this model species has been frequently explored in order to better understand how sexual selection and sexual conflict may operate and shape evolutionary trajectories. However, measuring individual flies can often be logistically complicated and inefficient, which can result in limited sample sizes. Instead, many experiments use large and/or small body sizes that are created by manipulating the developmental conditions experienced during the larval stages, resulting in "phenocopied" flies whose phenotypes resemble what is seen at the extremes of a population's size distribution. While this practice is fairly common, there has been remarkedly few direct tests to empirically compare the behaviour or performance of phenocopied flies to similarly-sized individuals that grew up under typical developmental conditions. Contrary to assumptions that phenocopied flies are reasonable approximations, this study found that both large and small-bodied phenocopied males frequently differed from their standard development equivalents in their mating frequencies, their lifetime reproductive successes, and in their effects on the fecundity of the females they interacted with. These results highlight the complicated contributions of environment and genotype to the expression of body size phenotypes and lead the authors to strongly urge caution in the interpretation of studies solely replying upon phenocopied individuals (Schang, 2023).

    Consequences of adaptation to larval crowding on sexual and fecundity selection in Drosophila melanogaster

    Sexual selection is a major force influencing the evolution of sexually reproducing species. Environmental factors such as larval density can manipulate adult condition and influence the direction and strength of sexual selection. While most studies on the influence of larval crowding on sexual selection are either correlational or single-generation manipulations, it is unclear how evolution under chronic larval crowding affects sexual selection. To answer this, the strength was measured of sexual selection on male and female Drosophila melanogaster that had evolved under chronic larval crowding for over 250 generations in the laboratory, along with their controls which had never experienced crowding, in a common garden high-density environment. Selection coefficients were measured on male mating success and sex-specific reproductive success, as separate estimates allowed dissection of sex-specific effects. Experimental evolution under chronic larval crowding was shown to decrease the strength of sexual and fecundity selection in males but not in females, relative to populations experiencing crowding for the first time. The effect of larval crowding in reducing reproductive success is almost twice in females than in males. This study highlights the importance of studying how evolution in a novel, stressful environment can shape adult fitness in organisms (Narasimhan, 2023).

    Gene-poor Y-chromosomes substantially impact male trait heritabilities and may help shape sexually dimorphic evolution

    How natural selection facilitates sexually dimorphic evolution despite a shared genome is unclear. The patrilineal inheritance of Y-chromosomes makes them an appealing solution. However, they have largely been dismissed due to their gene-poor, heterochromatic nature and because the additive genetic variation necessary for adaptive evolution is theoretically difficult to maintain. Further, previous empirical work has revealed mostly Y-linked sign epistatic variance segregating within populations, which can often impede adaptive evolution. To assess the evolutionary impact of Y-linked variation, this study established replicate populations in Drosophila simulans containing multiple Y-chromosomes (YN populations) or a single Y-chromosome variant (Y1 populations) drawn from a single population. Male and female heritabilities were assessed for several traits known to be influenced by Y-chromosomes, including the number of sternopleural bristles, abdominal bristles, sex comb teeth, and tibia length. A decrease in YN heritabilities compared with Y1 would be consistent with Y-chromosome variation being sign epistatic. A decrease in Y1 heritabilities would be consistent with Y-chromosome variation being additive, though additive-by-additive epistatic variation cannot be entirely dismissed. Female heritability estimates served as controls and were not expected to differ. It was found that male Y1 populations exhibited lower heritabilities for all traits except tibia length; consistent with Y-linked additivity (on average YN trait heritabilities were 25% greater than Y1). Female estimates showed no difference. These data suggest Y-chromosomes should play an important role in male trait evolution and may even influence sexually dimorphic evolution by shaping traits shared by both sexes (Nielsen, 2023).

    Evidence for stronger sexual selection in males than in females using an adapted method of Bateman's classic study of Drosophila melanogaster

    Bateman's principles, originally a test of Darwin's theoretical ideas, have since become fundamental to sexual selection theory and vital to contextualizing the role of anisogamy in sex differences of precopulatory sexual selection. Despite this, Bateman's principles have received substantial criticism, and researchers have highlighted both statistical and methodological errors, suggesting that Bateman's original experiment contains too much sampling bias for there to be any evidence of sexual selection. This study uses Bateman's original method as a template, accounting for two fundamental flaws in his original experiments, (a) viability effects and (b) a lack of mating behavior observation. Experimental populations of Drosophila melanogaster consisted of wild-type focal individuals and nonfocal individuals established by backcrossing the brown eye (bw-) eye-color marker-thereby avoiding viability effects. Mating assays included direct observation of mating behavior and total number of offspring, to obtain measures of mating success, reproductive success, and standardized variance measures based on Bateman's principles. The results provide observational support for Bateman's principles, particularly that (a) males had significantly more variation in number of mates compared with females and (b) males had significantly more individual variation in total number of offspring. A significantly steeper Bateman gradient was found for males compared to females, suggesting that sexual selection is operating more intensely in males. However, female remating was limited, providing the opportunity for future study to further explore female reproductive success in correlation with higher levels of remating (Davies, 2023).

    Engineering multiple species-like genetic incompatibilities in insects

    Speciation constrains the flow of genetic information between populations of sexually reproducing organisms. Gaining control over mechanisms of speciation would enable new strategies to manage wild populations of disease vectors, agricultural pests, and invasive species. Additionally, such control would provide safe biocontainment of transgenes and gene drives. This study demonstrates a general approach to create engineered genetic incompatibilities (EGIs) in the model insect Drosophila melanogaster. EGI couples a dominant lethal transgene with a recessive resistance allele. Strains homozygous for both elements are fertile and fecund when they mate with similarly engineered strains, but incompatible with wild-type strains that lack resistant alleles. EGI genotypes can also be tuned to cause hybrid lethality at different developmental life-stages. Further, it was demonstrated that multiple orthogonal EGI strains of D. melanogaster can be engineered to be mutually incompatible with wild-type and with each other. EGI is a simple and robust approach in multiple sexually reproducing organisms (Maselk, 2020).

    DrosoPhyla: Resources for Drosophilid Phylogeny and Systematics

    The vinegar fly Drosophila melanogaster is a pivotal model for invertebrate development, genetics, physiology, neuroscience, and disease. The whole family Drosophilidae, which contains over 4,400 species, offers a plethora of cases for comparative and evolutionary studies. Despite a long history of phylogenetic inference, many relationships remain unresolved among the genera, subgenera, and species groups in the Drosophilidae. To clarify these relationships, a set of new genomic markers was developed and a multilocus data set of 17 genes was assembled from 704 species of Drosophilidae. A species tree was inferred with highly supported groups for this family. Additionally, it was possible to determine the phylogenetic position of some previously unplaced species. These results establish a new framework for investigating the evolution of traits in fruit flies, as well as valuable resources for systematics (Finet, 2021).

    Pigmentation and fitness trade-offs through the lens of artificial selection.

    Pigmentation is a classic phenotype that varies widely and adaptively in nature both within and among taxa. Genes underlying pigmentation phenotype are highly pleiotropic, creating the potential for functional trade-offs. However, the basic tenets of this trade-off hypothesis with respect to life-history traits have not been directly addressed. In natural populations of Drosophila melanogaster, the degree of melanin pigmentation covaries with fecundity and several other fitness traits. To examine correlations and potential trade-offs associated with variation in pigmentation, replicate outbred populations were selected for extreme pigmentation phenotypes. Replicate populations responded rapidly to the selection regime and after 100 generations of artificial selection were phenotyped for pigmentation as well as the two basic fitness parameters of fecundity and longevity. The data demonstrate that selection on pigmentation resulted in a significant shift in both fecundity and longevity profiles. Selection for dark pigmentation resulted in greater fecundity and no pronounced change in longevity, whereas selection for light pigmentation decreased longevity but did not affect fecundity. These results indicate the pleiotropic nature of alleles underlying pigmentation phenotype and elucidate possible trade-offs between pigmentation and fitness traits that may shape patterns of phenotypic variation in natural populations (Rajpurohit, 2017).

    Evolutionary history of LTR-retrotransposons among 20 Drosophila species

    The presence of transposable elements (TEs) in genomes is known to explain in part the variations of genome sizes among eukaryotes. Even among closely related species, the variation of TE amount may be striking, as for example between the two sibling species, Drosophila melanogaster and D. simulans. However, not much is known concerning the TE content and dynamics among other Drosophila species. The sequencing of several Drosophila genomes, covering the two subgenus Sophophora and Drosophila, revealed a large variation of the repeat content among these species but no much information is known concerning their precise TE content. The identification of some consensus sequences of TEs from the various sequenced Drosophila species allowed to get an idea concerning their variety in term of diversity of superfamilies but the used classification remains very elusive and ambiguous. This study focused on LTR-retrotransposons because they represent the most widely represented class of TEs in the Drosophila genomes, describing the phylogenetic relationship of each LTR-retrotransposon family described in 20 Drosophila species, computing their proportion in their respective genomes and identifying several new cases of horizontal transfers. CAll these results give a clearer view on the evolutionary history of LTR retrotransposons among Drosophila that seems to be mainly driven by vertical transmissions although the implications of horizontal transfers, losses and intra-specific diversification are clearly also at play (Bargues, 2017).

    Retrotransposons are the major contributors to the expansion of the Drosophila ananassae Muller F element

    The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (~5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in Drosophila ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, the genome sequence was improved and the genes in a 1.4 Mb region of the D. ananassae F element, and a 1.7 Mb region from the D element were annotated for comparison. Transposons (particularly LTR and LINE retrotransposons) were found to be major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F element genes exhibit distinct characteristics compared to D element genes (e.g., larger coding spans, larger introns, more coding exons, lower codon bias), but these differences are exaggerated in D. ananassae. Compared to D. melanogaster, the codon bias observed in D. ananassae F element genes can primarily be attributed to mutational biases instead of selection. The 5' ends of F element genes in both species are enriched in H3K4me2 while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves understanding of how transposons can affect genome size and how genes can function within highly repetitive domains (Leung, 2017).

    Dissecting the satellite DNA landscape in three cactophilic Drosophila sequenced genomes

    Eukayote genomes are replete with repetitive DNAs. This class includes tandemly repeated satellite DNAs (satDNA) which are among the most abundant, fast evolving (yet poorly studied) genomic components. This study used high throughput sequencing data from three cactophilic Drosophila species, D. buzzatii, D. seriema and D. mojavensis, to access and study their whole satDNA landscape. Five satDNAs were identified, three previously described (pBuM, DBC-150 and CDSTR198) and two novel ones (CDSTR138 and CDSTR130). Only pBuM is shared among all three species. The satDNA repeat length falls within only two classes, between 130-200bp or between 340-390bp. FISH on metaphase and polytene chromosomes revealed the presence of satDNA arrays in at least one of the following genomic compartments: centromeric, telomeric, subtelomeric or dispersed along euchromatin. The chromosomal distribution ranges from a single chromosome to almost all chromosomes of the complement. Interspersion were revealed between pBuM and CDSTR130 in the microchromosomes of D. mojavensis. Phylogenetic analyses showed that the pBuM satDNA underwent concerted evolution at both interspecific and intraspecific levels. Based on RNAseq data, transcription activity was found for pBuM (in D. mojavensis) and CDSTR198 (in D. buzzatii) in all five analyzed developmental stages, most notably in pupae and adult males. These data revealed that cactophilic Drosophila present the lowest amount of satDNAs (1.9% to 2.9%) within the Drosophila genus reported so far (de Lima, 2017).

    Pervasive epigenetic effects of Drosophila euchromatic transposable elements impact their evolution

    Transposable elements (TEs) are widespread genomic parasites, and their evolution has remained a critical question in evolutionary genomics. This paper describes a study of the relatively unexplored epigenetic impacts of TEs and provides the first genome-wide quantification of such effects in D. melanogaster and D. simulans. Surprisingly, the spread of repressive epigenetic marks (histone H3K9me2) to nearby DNA occurs at >50% of euchromatic TEs, and can extend up to 20 kb. This results in differential epigenetic states of genic alleles and, in turn, selection against TEs. Interestingly, the lower TE content in D. simulans compared to D. melanogaster correlates with stronger epigenetic effects of TEs and higher levels of host genetic factors known to promote epigenetic silencing. This study demonstrates that the epigenetic effects of euchromatic TEs, and host genetic factors modulating such effects, play a critical role in the evolution of TEs both within and between species (Lee, 2017).

    Genomic analysis of P elements in natural populations of Drosophila melanogaster

    The Drosophila melanogaster P transposable element provides one of the best cases of horizontal transfer of a mobile DNA sequence in eukaryotes. Invasion of natural populations by the P element has led to a syndrome of phenotypes known as P-M hybrid dysgenesis that emerges when strains differing in their P element composition mate and produce offspring. This study compared estimates of genomic P element content with gonadal dysgenesis phenotypes for isofemale strains obtained from three worldwide populations of D. melanogaster to illuminate the molecular basis of natural variation in cytotype status. P element abundance estimated from genome sequences of isofemale strains is shown to be highly correlated across different bioinformatics approaches, but abundance estimates are sensitive to method and filtering strategies as well as incomplete inbreeding of isofemale strains. P element content was found to vary significantly across populations, with strains from a North American population having fewer P elements but a higher proportion of full-length elements than strains from populations sampled in Europe or Africa. Despite these geographic differences in P element abundance and structure, neither the number of P elements nor the ratio of full-length to internally-truncated copies is strongly correlated with the degree of gonadal dysgenesis exhibited by an isofemale strain. Thus, variation in P element abundance and structure across different populations does not necessarily lead to corresponding geographic differences in gonadal dysgenesis phenotypes. Finally, it was confirmed that population differences in the abundance and structure of P elements that are observed from isofemale lines can also be observed in pool-seq samples from the same populations. This work supports the view that genomic P element content alone is not sufficient to explain variation in gonadal dysgenesis across strains of D. melanogaster, and informs future efforts to decode the genomic basis of geographic and temporal differences in P element induced phenotypes (Bergman, 2017).

    In-Depth Satellitome Analyses of 37 Drosophila Species Illuminate Repetitive DNA Evolution in the Drosophila Genus

    Satellite DNAs (SatDNA) are ubiquitously present in eukaryotic genomes and have been recently associated with several biological roles. Understanding the evolution and significance of SatDNA requires an extensive comparison across multiple phylogenetic depths. This study combined the RepeatExplorer pipeline and cytogenetic approaches to conduct a comprehensive identification and analysis of the satellitome in 37 species from the genus Drosophila. 188 SatDNA-like families were identified, 112 of them being characterized for the first time. Repeat analysis within a phylogenetic framework has revealed the deeply divergent nature of SatDNA sequences in the Drosophila genus. The SatDNA content varied from 0.54% of the D. arizonae genome to 38.8% of the D. albomicans genome, with the SatDNA content often following a phylogenetic signal. Monomer size and guanine-cytosine-content also showed extreme variation ranging 2-570 bp and 9.1-71.4%, respectively. SatDNA families are shared among closely related species, consistent with the SatDNA library hypothesis. However, the emergence of species-specific SatDNA families was uncovered through amplification of unique or low abundant sequences in a lineage. Finally, genome sizes of the Sophophora subgenus were found to be positively correlated with transposable element content, whereas genome size in the Drosophila subgenus is positively correlated with SatDNA. This finding indicates genome size could be driven by different categories of repetitive elements in each subgenus. Altogether, this study conducted the most comprehensive satellitome analysis in Drosophila from a phylogenetic perspective and generated the largest catalog of SatDNA sequences to date, enabling future discoveries in SatDNA evolution and Drosophila genome architecture (de Lima, 2022).

    Phenotypic plasticity through transcriptional regulation of the evolutionary hotspot gene tan in Drosophila melanogaster

    Phenotypic plasticity is the ability of a given genotype to produce different phenotypes in response to distinct environmental conditions. Phenotypic plasticity can be adaptive. Furthermore, it is thought to facilitate evolution. Although phenotypic plasticity is a widespread phenomenon, its molecular mechanisms are only beginning to be unravelled. Environmental conditions can affect gene expression through modification of chromatin structure, mainly via histone modifications, nucleosome remodelling or DNA methylation, suggesting that phenotypic plasticity might partly be due to chromatin plasticity. As a model of phenotypic plasticity, abdominal pigmentation was studied of Drosophila melanogaster females, which is temperature sensitive. Abdominal pigmentation is indeed darker in females grown at 18 degrees C than at 29 degrees C. This phenomenon is thought to be adaptive as the dark pigmentation produced at lower temperature increases body temperature. This study showed that temperature modulates the expression of tan (t), a pigmentation gene involved in melanin production. t is expressed 7 times more at 18 ° C than at 29 &176; C in female abdominal epidermis. Genetic experiments show that modulation of t expression by temperature is essential for female abdominal pigmentation plasticity. Temperature modulates the activity of an enhancer of t without modifying compaction of its chromatin or level of the active histone mark H3K27ac. By contrast, the active mark H3K4me3 on the t promoter is strongly modulated by temperature. The H3K4 methyl-transferase involved in this process is likely Trithorax, since it regulates t expression and the H3K4me3 level on the t promoter and also participates in female pigmentation and its plasticity. Interestingly, t was previously shown to be involved in inter-individual variation of female abdominal pigmentation in Drosophila melanogaster, and in abdominal pigmentation divergence between Drosophila species. Sensitivity of t expression to environmental conditions might therefore give more substrate for selection, explaining why this gene has frequently been involved in evolution of pigmentation (Gibert, 2016).

    On the long-term stability of clines in some metabolic genes in Drosophila melanogaster

    Very little information exists for long-term changes in genetic variation in natural populations. This study took the unique opportunity to compare a set of data for SNPs in 15 metabolic genes from eastern US collections of Drosophila melanogaster that span a large latitudinal range and represent two collections separated by 12 to 13 years. This was expanded to a 22-year interval for the Adh gene and approximately 30 years for the G6pd and Pgd genes. During these intervals, five genes showed a statistically significant change in average SNP allele frequency corrected for latitude. While much remains unchanged, five genes were seen that wx latitudinal clines have been lost or gained and two where the slope significantly changes. The long-term frequency shift towards a southern favored Adh S allele reported in Australia populations is not observed in the eastern US over a period of 21 years. There is no general pattern of southern-favored or northern-favored alleles increasing in frequency across the genes. This observation points to the fluid nature of some allelic variation over this time period and the action of selective responses or migration that may be more regional than uniformly imposed across the cline (Cogni, 2017).

    Genomic variation predicts adaptive evolutionary responses better than population bottleneck history

    The relationship between population size, inbreeding, loss of genetic variation and evolutionary potential of fitness traits is still unresolved, and large-scale empirical studies testing theoretical expectations are surprisingly scarce. This study presents a highly replicated experimental evolution setup with 120 lines of Drosophila melanogaster having experienced inbreeding caused by low population size for a variable number of generations. Genetic variation in inbred lines and in outbred control lines was assessed by genotyping-by-sequencing (GBS) of pooled samples consisting of 15 males per line. All lines were reared on a novel stressful medium for 10 generations during which body mass, productivity, and extinctions were scored in each generation. In addition, egg-to-adult viability was investigated in the benign and the stressful environments before and after rearing at the stressful conditions for 10 generations. Strong positive correlations were found between levels of genetic variation and evolutionary response in all investigated traits, and showed that genomic variation was more informative in predicting evolutionary responses than population history reflected by expected inbreeding levels. It was also found that lines with lower genetic diversity were at greater risk of extinction. For viability, the results suggested a trade-off in the costs of adapting to the stressful environments when tested in a benign environment. This work presents convincing support for long-standing evolutionary theory, and it provides novel insights into the association between genetic variation and evolutionary capacity in a gradient of diversity rather than dichotomous inbred/outbred groups (Orsted, 2019).


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