John Gerhart and Marc Kirschner
Cells, Embryos, And Evolution
1997
Blackwell Science
ISBN 0-86542-574-4

• Contents
• Preface

Table of Contents

1. The surprising conservation of cellular processes
2. Contingency
3. Regulatory linkage
4. The exploratory behaviour of biological systems
5. Novelty
6. Conditionality and compartmentalization
7. Body plans
8. Axis specification and reproductive strategies
9. Developmental flexibility and robustness
10. Evolutionary diversification of the body plan
11. Evolution and evolvability

Preface

Twelve years ago we began a monograph on cell and developmental biology. At that time it was not yet widely appreciated how similar at that these mechanisms rest on common cellular principles. As we began to write, a flood of new experimental results convinced everyone of the underlying conservation of embryonic mechanisms. The novelty of our proposed book faded and we abandoned it, with a small exception: in the last chapter we had hoped to discuss the differences, not the similarities, among organisms, under the general heading of the "Evolution of Development". In many ways the increasing evidence for conservation had made the origin of differences more interesting, and thus the final chapter of our unwritten book became the beginning of a new one.

We were not the only ones intrigued by conservation and evolution. Students in our laboratories and in our courses were often uncomfortable with taxonomic specializations. This generation of students, as no other before it, had been schooled in the generalities of biology. For them, biology, built upon chemistry, built upon physics, was worth studying when it was general, and was less interesting when it was specific to taxa. The new results of developmental biology, showing unexpected conservation in the embryonic development of distantly related organisms, reinforced a prejudice towards the study of general mechanisms. Yet these students, discomforted as they were to confront anatomical and structural specializations, could not completely avoid a fascination with the peculiarities of the organisms they studied. Hence, they too were drawn to evolution.

There is, in fact, no easy way to tease out embryological generalities from embryological differences. Both are due to selection and every process is a mixture of conservation and specialization. Yet as details were accumulating in cell biology, genetics, biochemistry, and developmental biology, clues were also emerging not only about why cellular processes are the way they are but also how they come to differ among organisms. When we looked at the last chapter of our ill-fated book, we saw an opportunity that was unimaginable 12 years ago: to begin to explain on a cellular and developmental level how organisms came to be different.

Charles Darwin and the evolutionary biologists who later clarified and rethought his ideas in modern terms had already provided the ultimate mechanisms for evolution in the theory of heritable variation and natural selection, and populations geneticists had already explained how genetic differences in populations could be selected and lead to evolutionary change. Yet none of these approaches could describe how organisms changed on a cellular level in the course of evolution. We can observe that the beak of a finch is modified when the food source changes, but we do not know how the cells and their products actually cause the beak to vary its shape. Are there many ways to change a beak? Are there many possible shapes that could be produced? How does the rest of the head manage to accommodate to the change of the beak? How many genetic changes does it take to change a beak? If we sequence the genome could we tell the consequential changes from the unimportant ones? Have birds over time developed better and better ways to change their beaks? To answer these questions, one needs to understand the substrate upon which selection acts, the cellular and developmental processes of the organism.

The mechanisms of cellular change are the missing links that still leave a sense of doubt or mystery in natural selection. We can imagine whales returning to the sea and losing their legs, or birds transforming their digits into wings, but there is a lingering desire to know what genetic and cellular changes actually occurred along the way. For a long time we have had a good theory of genotypes and genotypic change in biology as well as a good theory of natural selection. What has been lacking, as many biologists have appreciated for the last several decades, is a goo theory of phenotypes, especially how genetic change produces phenotypic change.

This book takes a tour through modern cell and developmental biology, but it is not a random walk. Our intention was to look for those cellular processes that are most important for evolutionary change. We first confront the question of conservation and diversity, examining now conservation might be used in biology to produce diversity. Investigating diversity in conserved systems, we find that although there are simple and ad hoc ways in which processes are controlled, there are also powerful general mechanisms for achieving control. Particularly important in evolutionary change are signaling, cytoskeletal, and transcription systems, all of which can easily alter connectivity of processes within the organism. To understand protein evolution we must understand how the use of proteins changes, which brings us quickly to selection for new uses. In multicellularity we confront the strategies that allow groups of cells to evolve in partial independence from other groups and from that, the strategies for generating multicellular patterns. The robustness of pattern generation and its capacity to change seem to be related properties. In tracing the evolutionary modification of the body plans of the major phyla we see the importance of adapting to the reproductive modifications of the egg. Finally, we see that many of the same multicellular and cellular modifications employed in early development are reapplied in the modifications of the body plan, in the head, and in the appendages. We are left with the strong impression that evolution shapes the mechanisms of cell biology just as cell biology shapes the responses of the organisms to selection. Evolutionary mechanisms and cellular mechanisms are intertwined; each is necessary for the other and the study of one enriches the study of the other.

Theodosius Dobzhansky (1900-1975) said, "Nothing in biology makes sense except in the light of evolution." (American Biology Teacher, Volume 35, 1973). Yet for most molecular biologists, Dobzhansky's claim is unconvincing. To understand cell function, knowledge of evolution is much less important that knowledge of chemistry. Yet it is not enough to understand how a given process works; complete understanding only comes with knowledge of why a process has the properties it has and not others. Those properties have shaped evolutionary change and been shaped by it. Not all outcomes of mutation are equally likely and, as organisms evolve, their responses to mutation must also evolve and affect the next steps of evolution. Today Dobzhansky might be tempted to say, "Nothing in evolution makes sense except in the light of cell biology." In Dobzhansky's time it was inconceivable that morphology, behavior and physiology could be explainable in terms of the actual products of the genes that he manipulated. Dobzhansky died at a time when Drosphilia developmental genetics had itself almost expired. A generation later, Drosphilia developmental genetics would re-emerge as a unifying force in embryology and , as we will show, in evolution as well. With it, and with the explosion in molecular biology, cell biology could assert itself in evolutionary thought and allow a reinterpretation of evolution as a cellular process.

Writing this book involved many compromises and choices. If the book is not always easy to read, it is partly because we have chosen to explain phenomena in their own terms and not in metaphors. Describing biochemistry requires describing pathways, molecular biology requires protein and nucleic acid sequences, cell biology requires cellular structures, and developmental biology requires an often exasperating diversity of anatomical terms and molecules. We have called upon important fields of biology, such as paleontology, evolutionary theory, neurophysiology, comparative anatomy, and immunology, each with its own conventions and vocabulary. It is ironic that the ideas behind evolution are often so much simpler than words needed to explain them. Yet without the details there is no way the reader can test our claims or question our generalizations. To allow readers to avoid some of the dense explanations, we have provided many diagrams and photographs which in most cases summarize a section in simple and economic terms.

There are other choices we had to make as well. We admit to, but are not proud of, an unavoidable phylogenetic bias. This is a book primarily about the cell biology, development, and evolution of metazoan organisms for the Early Cambrian Period (550 million years ago) to the present. We offer nothing on the origin of life, or on higher plants, algae and many other eukaryotes. Prokaryotes are used only as a foil for elucidating the properties of eukaryotes. As evolutionary history this book is therefore incomplete. There are three reasons for the omissions. The first is the length of the book: just explicating the embryology of metazoans to a level where we could examine their molecular and cellular differences consumed considerable space. The second is limits of our knowledge. We had already departed from familiar shores; there were bounds to our courage. The third is that the corpus of molecular, cellular, and developmental biology today was not created by questions of evolutions. Information about cellular evolution is largely a fortuitous by-product of a worldwide investment in biomedical science. Though we might bemoan a preoccupation with only six of seven organisms as models for human disease, we probably should be grateful that the choice was a phylogenetically diverse as it was. It should be relatively easy to broaden molecular studies to other phyla and kingdoms in the future, if there is monetary support.

The cell biology of evolution is a new subject, so we encourage our readers to offer corrections and comments; to this end we have set up a web page. We will post any serious and scholarly comments, points of discussion, or suggestions for revisions at:

http://cbweb.med.harvard.edu/cee.html

Comments should be sent to us by e-mail at: [email protected]