The Shape of Life: Genes, Development, and the Evolution of Animal Form.
During the happy period of the Modern Synthesis, there was some exchange of ideas. I had the good fortune at that time to be taught not only by J.B.S. Haldane and palaeontologist D.M.S. Watson, but by Gavin de Beer, author of Embryos and Ancestors, and one of the few developmental biologists to contribute to the synthesis. Essentially, de Beer's theme was that morphology can be altered by altering the rates of different processes, and that genes can alter rates. This idea does illuminate some evolutionary processes. For example, our own recent evolution is illuminated by the idea of neoteny. But the idea of heterochrony is, I think, too narrow to advance us very far. An essay on heterochrony written today would not contain many illustrative examples that were not already familiar to de Beer.
Recent events, however, maintain the hope that all this will change. We are living through a revolution in developmental genetics. It has been possible, for over 50 years, to identify gene loci which, if they mutate, cause dramatic changes in early development, and hence in adult morphology. What is new is that it is now possible, in the mouse, Drosophila, Arabidopsis, Caenorhabditis, and other convenient organisms, to sequence such genes, to find their homologues in other organisms, to find the sites of their earliest activity in time and space, to observe the effects of inactivating them, and in some cases, to transfer them between organisms and study their effects. The time is approaching to decide what this avalanche of new knowledge can tell us about evolution.
Raff's book will help us to decide. He is admirably placed to do this. He, himself, has worked in two relevant areas - the relation between phylogeny as deduced from molecular sequences and the major morphological types of animals, and changes in patterns of development within a taxon (in his case, echinoderms). He has made a serious effort to master the bewildering complexities of modern developmental genetics. He has an open mind, and is determined to build bridges between disciplines. As a population geneticist, I occasionally found him unjustifiably typological, as when he writes, "Each species is genetically distinct," or when he assures the reader, several times, that there are 35 phyla. Surely this is a description of the present prejudices of taxonomists, rather than a fact about the world, but this is perhaps unfair. Despite his occasional lapses into typology, he does understand natural selection.
He is at his best when writing about his own work. He and his colleagues have played a leading part in the use of molecular data to unravel the phylogenetic relationships between the main groups of animals. Perhaps the main lesson to emerge from this work is that the classical comparative anatomists and developmental biologists got it right. Despite being trained in comparative anatomy, or perhaps because of it, I was distrustful of some of the morphological criteria - for example, diploblastic versus triploblastic, or proterostome versus deuterostome - used in reconstructing phylogeny. It seems that my distrust was unjustified; molecular data have, by and large, confirmed phylogenies based on morphology.
A second field in which Raff has worked is the development of echinoderms. Most echinoderms have a feeding larval form, the pluteus larva, but some develop directly into an adult urchin. Phylogenetic studies show that direct development has evolved repeatedly. Raff's comparison of two species of urchins, Heterocidaris tuberculata, which has a small egg of 90 [Mu] and a feeding pluteus, and H. erythrogamma, with an egg of 430 [Mu] and direct development, gives a fascinating picture of how rapid change in development can occur without significant change in adult form.
In contrast, I did not find what he has to say about recent developmental genetics particularly helpful. His account of recent research in this field is not concentrated in one place in the book, but dotted throughout the text when it is relevant to the topic being discussed. This sounds a reasonable procedure, but it has the effect that accounts are brief, disjointed and hard to follow. When I was already familiar with a topic, I could follow his argument, but when I was not, I was none the wiser after reading it. Sadly, I do not think that Raff has written the book which, perhaps unreasonably, I had hoped for - a book which would tell me the significance for evolutionary biology of recent developmental genetics.
There are, as I see it, two aspects to this problem, both concerned with conservatism in evolution. The problem was well summarized in a recent paper by Slack et al. (1993), a paper that Raff discusses. These authors suggest that the common defining feature of animals - a characteristic which they call the "zootype" - is the existence of a series of homologous genes, the Hox gene cluster, the first to be discovered being the homeobox-containing genes of Drosophila, which specify the differentiation of varying structures along the antero-posterior axis of the body, by switching on a cascade of other genes. The curious and striking fact is that these genes have retained their structure. For example, the most anteriorly expressed gene in Drosophila is more similar to the most anteriorly expressed gene in the mouse than it is to other Hox genes in Drosophila, although the structures they elicit in Drosophila and the mouse are quite different. In other words, a signal has been conserved, despite changes in the detailed responses to that signal. A more recently discovered example of such conservation (Quirring et al. 1994) is the homology between the eyeless gene in Drosophila and the pax-6 gene in the mouse, which plays a role in eliciting the development of an eye, although no one, I hope, would draw parallels between the structure of the eye in vertebrates and arthropods.
I confess I do not understand this conservation of a signal, as opposed to the conservation of a functional organ. The form of a haemoglobin molecule, or a bird's wing, is conserved because it has adapted to perform a function, which would be lost if the form was changed. In so far as the form of a signal is arbitrary, this explanation does not work; one can use the same kind of switch to operate a television or a hair dryer. Of course, what precisely a switch does depends on what device it is connected to. By analogy, what a regulator gene does depends on what other genes have promoters to which its product can bind. One might therefore argue that regulator genes, or some of them, are conserved because to change such a gene requires that one simultaneously change the gene and its targets. It is always hard to make two coordinated changes by natural selection, particularly in a sexual population. This may be the right answer, but I suspect there may be more to it, if only because we know that regulator genes do acquire new meanings. For example, Hox genes also play a role in limb development.
A second conservatism, mentioned by Slack et al. and discussed at length by Raff, is of the "phylotype," a morphology through which all members of a phylum pass, although they may differ substantially from one another both earlier in development and later. A familiar example is the pharyngula stage of vertebrates, with a notochord, hollow dorsal nerve cord, segmented somites, and pharynx with gill slits. The early and late differences between, say, a sparrow and a codfish are easy to explain adaptively: early differences arise, in part, because of differences in the amount of yolk in the egg, and later differences are imposed by the problems of living in air or water, respectively. But why the convergence on the phylotype? Raff suggests that it is because the phylotype marks the transition between the stage when developmental processes are global, involving cell migration, and ending when the main body parts exist as blocks of undifferentiated cells, and a stage when the development of different parts proceeds to some degree independently. This seems to me to be along the right lines.
In summary, I think we may be on the eve of a new synthesis in evolutionary biology. That synthesis will arise by incorporating developmental genetics. By telling us how changes in genes can cause changes in morphology, conversation will be facilitated between population biologists and palaeontologists, which has been too infrequent for too long. I do not think that Raff has achieved that synthesis, but this scholarly and thoughtful book is a step toward it.
SLACK, J.M.W., P.W.H. HOLLAND, AND C. F. GRAHAM. 1993. The zootype and the phylotypic stage. Nature 361:490-492.
QUIRRING, R., U. WALLDORF, AND W. GEHRING. 1994. Homology of the eyeless gene in Drosophila to the small eye gene in mice and aniridia in humans. Science 265:785-789.