1937; Hamburger, 1980; Allen, 1986; Sapp, 1986; Gilbert et al., 1996; Burian 2000;. Amundson ... to specific rules and mutated at particular rates. In contrast, the ...
Scott F. Gilbert Department of Biology Swarthmore College Swarthmore, PA 19081 USA
Richard M. Burian Department of Philosophy Virginia Polytechnic Institute and State University Blacksburg, VA 24061-0126
For much of the twentieth century, Mendelian genetics and evolutionary biology ignored (“black-boxed”) the developmental mechanisms that produce variation (Harrison, 1937; Hamburger, 1980; Allen, 1986; Sapp, 1986; Gilbert et al., 1996; Burian 2000; Amundson, 2000). As a result, embryology and developmental biology were not included in the so-called Modern (or “neo-Darwinian”) Synthesis in evolutionary biology. Thus, in a major founding document of that synthesis, Theodosius Dobzhansky (1937) redefined evolution as change of allele frequency. Although several founders of the population genetic approach to evolution did not accept Dobzhansky’s subsumption of evolution within population genetics, their objections did not turn on the need to include development within the synthesis, but on the need to account for population distributions, population sizes, and lineage splitting. Population genetics became the predominant explanatory mode for evolutionary biology, and by 1951, Dobzhansky (p. 16) could confidently declare, “Evolution is a change in the genetic composition of populations. The study of mechanisms of evolution falls within the province of populations genetics.” Similarly, Ernst Mayr, (1980, p. 9-10), who rejected the definition of evolution in terms
of change of gene frequency, wrote that “…the clarification of the biochemical mechanism by which the genetic program is translated into the phenotype tells us absolutely nothing about the steps by which natural selection had built up the particular genetic program.” Until recently, developmental genetics had little to offer evolutionary biology except some ideas. However, since the 1980s, the mechanisms of differential gene expression have been elucidated, and the far-reaching effects of changes in gene expression patterns have been explored. Developmental biology is now providing evolutionary biology with tools to understand the contexts and identities of genes that are important for generating variation and of the contextual factors that regulate their expression. Developmental genetics has also cleared up some misconceptions about evolution. For example, there was a consensus that “the search for homologous genes is quite futile except in very close relative.” xx check relatives (Mayr, 1966, p. 609, quoting Dobzhansky). Developmental geneticists disproved this view with the discovery that many of the genes encoding the developmental “toolbox” of paracrine and transcription factors were conserved between protostomes and deuterostomes. Evolutionary developmental biology is now analyzing the proximate mechanisms responsible for some of the inherited variations studied by population geneticists. It has shown that some of the mechanisms that produce developmental variations have been coopted into novel contexts, where they have played a significant role in evolutionary innovation (an idea called "bricolage"; see Jacob, 1977; Duboule and Wilkins, 1998). For example, differences in the expression of Hox genes can determine bristle pattern differences in Drosophila and axial skeleton differences in vertebrates and arthropods (Gaunt, 1994; Averof and Akam, 1995; Burke et al., 1995; Averof and Patel, 1997). Genes responsible for primitive characters can be utilized for new traits, such as when genes responsible for segmentation and neurogenesis are used for making eyespots of butterfly wings (Keys et al., 1999). Thus, it is reasonable to expect that the differences that transformed a flightless insectivore into a bat or a shell-less reptile into a turtle were produced by regulatory genes acting within the embryo. The identities of these genes and the manner of their expression, studied by developmental genetics, currently constitute a central theme in evolutionary developmental biology.
There are important historical differences between the account of genes utilized by the population genetic approach to evolution that was employed in the Modern Synthesis, and the account of genes in developmental genetics that is employed in evodevo. (see also Gilbert, 2000). First, the genes of classical population genetics were uncovered by transmission patterns, typically captured in mathematical abstractions. The physical structure of a gene was not crucial for the identification of alleles A and a, hypothesized or detected by their effects, as long as they were stably inherited according to specific rules and mutated at particular rates. In contrast, the genes of developmental genetics are defined by conserved DNA sequences with specific regulatory regions, coding regions, and intron/exon boundaries. Second, the genes of population genetics are recognized by the phenotypic differences caused by their various alleles. The very meaning of the term “allele” is tied to variants of a gene producing different phenotypes within a population. Developmental genes were recognized by the roles they played in controlling specific developmental processes, by the interactions of their products with DNA, and by their structural similarities in different taxa. Many developmental genes were identified using polymerase chain reactions to identify closely similar sequences and then testing for homology, a technique now being used in population genetics. Third, population geneticists focused primarily on variation in the frequency of alleles within populations or species, whereas developmental geneticists focused primarily on variations in developmental gene expression between taxa. Fourth, the population genetic approach sought to explain adaptation by natural selection (“survival of the fittest,”) tempered by drift, meiotic drive, etc., whereas the developmental genetic approach sought to explain phylogeny (“arrival of the fittest”) and the production of novelties. Fifth, the population genetics approach to evolution focuses primarily on genes that affect adults and impact on competition for reproductive success, whereas the developmental genetics approach to evolution focuses on genes expressed during development, their interactions, and their impact on the ontogeny of the organism. These approaches, whose differences we have highlighted, are being integrated in evo-devo. Gene expression is regulated contextually and often epigenetically, so genes characterized by their effects are not seen as autonomous. At the same time, if they are to survive, developmental genes and their variants, like all genes, must have net effects that
either facilitate or, at least, do not hinder, reproductive survival within their organismal and populational contexts. Accordingly, developmental genes must be analyzable by the approaches taken by both developmental and population genetics. Which tools are appropriate depends on the problem at hand, e.g., whether we are examining embryonic development or phylogenetic histories. But in the end we must be able to track genes and their interactions within developmental contexts and in lineages of transmission through both generational and evolutionary time. One of the first investigators to suggest merging the approaches of developmental and population genetics, C. H. Waddington concluded that evolutionary biology needed to study those processes that get from the genotype to the phenotype--the “epigenetics of development.” Following Goldschmidt (1940), Waddington (1953, p. 190) declared, “Changes in genotypes only have ostensible effects in evolution if they bring with them alterations in the epigenetic processes by which phenotypes come into being; the kinds of change possible in the adult form of an animal are limited to the possible alterations in the epigenetic system by which it is produced.” Waddington distinguishes here selection working on adults from the selection working during development, and he claimed that both these modes of evolution work together to produce species adapted to particular environments. The evo-devo model of evolution follows from Waddington’s notions of selection of alternative epigenetic processes during development. Evolutionary developmental biology does not seek to replace the Modern Synthesis. Rather, the consensus of evolutionary developmental biologists is that their discipline complements and extends the Modern Synthesis, and that no full account of evolutionary phenomena can be achieved without both population genetic and developmental genetic approaches. Most evolutionary developmental biologists expect that the bricolage necessary for the generation of new morphologies is consistent with the traditional microevolutionary mechanisms of mutation, recombination, and meiotic drive. In addition, they would emphasize the importance of gene duplication and divergence in allowing cooption, the roles of changing the time and place of gene expression to produce variation, and the roles of gamete binding proteins as a mechanism of reproductive isolation (Metz and Palumbi, 1996; Lyon and Vacquier, 1999). These mechanisms are now being taken seriously by population geneticists, as well.
The role of mutations in regulatory genes have long been assumed to be important in producing major phylogenetic changes, but evidence of this was provided only recently. During the evolution of arthropods, the Ser/Thr domain of the Ubx protein in the common ancestor of crustaceans and insects was replaced by an alanine-rich region that gave it a new activity. This mutation converted the Ubx protein into a repressor of the Distal-less gene. This mutation is found in all insects but is absent in crustaceans, spiders, centipedes, and onychophorans. The successive replacement of the serine/threonine region by the poly-alanine repression domain is correlated with and may have facilitated the patterns of segmental diversity found in insects (Galant and Carroll, 2002; Ronschaugen et al., 2002). Both the population genetic account of evolution and the account rooted in the genetics of development are required to produce an analysis of intraspecific and interspecific variation. Intraspecific variation provides the raw material for the population genetic account of evolution and thus is the pivot of natural selection. However, many of the genes producing such normally occurring variations are active in development, although they are not well characterized. Indeed, a major limitation of the attempt to forge a new synthesis has been the failure to identify alleles of paracrine and transcription factor genes (including their regulatory sequences) which may be responsible for variation in the amounts or efficiencies of paracrine or transcription factors, and which could then be studied at the population level. Amundson (2001) predicts (and we agree) that until developmental biology increases its attention to intraspecific variation, developmental approaches will not interest mainstream evolutionary biologists. Such steps are being taken (see Kopp et al., 2000; MacDonald and Hall, 2001; Johnson and Porter, 2001) and are necessary if evolutionary developmental biology is to provide the tools for studying the ways by which microevolutionary processes relate to macroevolutionary differences. These new tools allow us to employ new methods in attempting to answer old questions of phylogeny and novel morphology that provided a starting point for Darwin’s theory. Moreover, we seek to synthesize the same modes of thinking that Darwin himself had to bring together; the interaction of form (“unity of type”) and function (adaptation to the “conditions of existence”) were integrated into “descent with modification” through
“natural selection”. Darwin (1859, p. 206) wrote that “natural selection acts by either now adapting the varying parts of each being to its organic and inorganic conditions of life; or by having adapted them during long-past periods of time, being in all cases subjected to the several laws of growth. Hence, in fact, the law of the Conditions of Existence is the higher law; as it includes, through the inheritance of former adaptations, that of Unity of Type.” Recent differences between population genetic and developmental genetic approaches to evolution can be seen as continuing the debate over the relative importance of function versus structural homology (Amundson, 1998). In comparison with the population genetic tradition, evo-devo elevates the importance of structural homologies, but remains within a generally Darwinian framework. Darwin wrote (1859, p. 403), “What can be more curious than that the hand of a man, formed for grasping, that of a mole, for digging, the leg of a horse, the paddle of a porpoise, and the wing of a bat should all be constructed on the same pattern and should include similar bones, and in the same relative positions?” To account for these and similar instances of descent with modification, new accounts of the generation of form, now being produced within evolutionary developmental biology, need to be completed and integrated with the findings and tools of both developmental and population genetics. This new evolutionary synthesis would be able to account not only for the mechanisms by which phenotypes are selected but also for the mechanisms by which certain phenotypes emerge.
Acknowledgements: We wish to thank Drs. Ron Amundson, Marjorie Grene, Sahotra Sarkar, Günter Wagner, and the editors for their critical comments on earlier drafts of this essay
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