Evolutionary developmental biology

Evolutionary developmental biology (evolution of development or informally, evo-devo) is a field of biology that compares the developmental processes of different organisms to determine the ancestral relationship between them, and to discover how developmental processes evolved. It addresses the origin and evolution of embryonic development; how modifications of development and developmental processes lead to the production of novel features, such as the evolution of feathers; the role of developmental plasticity in evolution; how ecology impacts in development and evolutionary change; and the developmental basis of homoplasy and homology.

Although interest in the relationship between ontogeny and phylogeny extends back to the nineteenth century, the contemporary field of evo-devo has gained impetus from the discovery of genes regulating embryonic development in model organisms. General hypotheses remain hard to test because organisms differ so much in shape and form.

Nevertheless, it now appears that just as evolution tends to create new genes from parts of old genes (molecular economy), evo-devo demonstrates that evolution alters developmental processes to create new and novel structures from the old gene networks (such as bone structures of the jaw deviating to the ossicles of the middle ear) or will conserve (molecular economy) a similar program in a host of organisms such as eye development genes in molluscs, insects, and vertebrates. Initially the major interest has been in the evidence of homology in the cellular and molecular mechanisms that regulate body plan and organ development. However more modern approaches include developmental changes associated with speciation.

Basic principles
Charles Darwin's theory of evolution is based on three principles: natural selection, heredity, and variation. At the time that Darwin wrote, the principles underlying heredity and variation were poorly understood. In the 1940s, however, biologists incorporated Gregor Mendel's principles of genetics to explain both, resulting in the modern synthesis. It was not until the 1980s and 1990s, however, when more comparative molecular sequence data between different kinds of organisms was amassed and detailed, that an understanding of the molecular basis of the developmental mechanisms has arisen.

Developmental mechanisms are not understood sufficiently to explain which kinds of phenotypic variation can arise in each generation from variation at the genetic level. Evolutionary developmental biology studies how the dynamics of development determine the phenotypic variation arising from genetic variation and how that affects phenotypic evolution (especially its direction). At the same time evolutionary developmental biology also studies how development itself evolves.

Thus, the origins of evolutionary developmental biology come from both an improvement in molecular biology techniques as applied to development, and the full appreciation of the limitations of classic neo-Darwinism as applied to phenotypic evolution. Some evo-devo researchers see themselves as extending and enhancing the modern synthesis by incorporating into it findings of molecular genetics and developmental biology. Others, drawing on findings of discordances between genotype and phenotype and epigenetic mechanisms of development, are mounting an explicit challenge to neo-Darwinism.

Evolutionary developmental biology is not yet a unified discipline, but can be distinguished from earlier approaches to evolutionary theory by its focus on a few crucial ideas. One of these is modularity: as has been long recognized, plants and animal bodies are modular: they are organized into developmentally and anatomically distinct parts. Often these parts are repeated, such as fingers, ribs, and body segments. Evo-devo seeks the genetic and evolutionary basis for the division of the embryo into distinct modules, and for the partly independent development of such modules.

Another central idea is that some gene products function as switches whereas others act as diffusible signals. Genes specify proteins, some of which act as structural components of cells and others as enzymes that regulate various biochemical pathways within an organism. Most biologists working within the modern synthesis assumed that an organism is a straightforward reflection of its component genes. The modification of existing, or evolution of new, biochemical pathways (and, ultimately, the evolution of new species of organisms) depended on specific genetic mutations. In 1961, however, Jacques Monod, Jean-Pierre Changeux and François Jacob discovered within the bacterium Escherichia coli a gene that functioned only when "switched on" by an environmental stimulus. Later, scientists discovered specific genes in animals, including a subgroup of the genes which contain the homeobox DNA motif, called Hox genes, that act as switches for other genes, and could be induced by other gene products, morphogens, that act analogously to the external stimuli in bacteria. These discoveries drew biologists' attention to the fact that genes can be selectively turned on and off, rather than being always active, and that highly disparate organisms (for example, fruit flies and human beings) may use the same genes for embryogenesis (e.g., the genes of the "developmental-genetic toolkit", see below), just regulating them differently.

Similarly, organismal form can be influenced by mutations in promoter regions of genes, those DNA sequences at which the products of some genes bind to and control the activity of the same or other genes, not only protein-specifying sequences. This finding suggested that the crucial distinction between different species (even different orders or phyla) may be due less to differences in their content of gene products than to differences in spatial and temporal expression of conserved genes. The implication that large evolutionary changes in body morphology are associated with changes in gene regulation, rather than the evolution of new genes, suggested that Hox and other "switch" genes may play a major role in evolution, something that contradicts the neo-darwinian synthesis.

Another focus of evo-devo is developmental plasticity, the basis of the recognition that organismal phenotypes are not uniquely determined by their genotypes. If generation of phenotypes is conditional, and dependent on external or environmental inputs, evolution can proceed by a "phenotype-first" route, with genetic change following, rather than initiating, the formation of morphological and other phenotypic novelties. The case for this was argued for by Mary Jane West-Eberhard in her 2003 book Developmental plasticity and evolution.

History
An early version of recapitulation theory, also called the biogenetic law or embryological parallelism, was put forward by Étienne Serres in 1824–26 as what became known as the "Meckel-Serres Law" which attempted to provide a link between comparative embryology and a "pattern of unification" in the organic world. It was supported by Étienne Geoffroy Saint-Hilaire as part of his ideas of idealism, and became a prominent part of his version of Lamarckism leading to disagreements with Georges Cuvier. It was widely supported in the Edinburgh and London schools of higher anatomy around 1830, notably by Robert Edmond Grant, but was opposed by Karl Ernst von Baer's embryology of divergence in which embryonic parallels only applied to early stages where the embryo took a general form, after which more specialised forms diverged from this shared unity in a branching pattern. The anatomist Richard Owen used this to support his idealist concept of species as showing the unrolling of a divine plan from an archetype, and in the 1830s attacked the transmutation of species proposed by Lamarck, Geoffroy and Grant. In the 1850s Owen began to support an evolutionary view that the history of life was the gradual unfolding of a teleological divine plan, in a continuous "ordained becoming", with new species appearing by natural birth.

In On the Origin of Species (1859), Charles Darwin proposed evolution through natural selection, a theory central to modern biology. Darwin recognised the importance of embryonic development in the understanding of evolution, and the way in which von Baer's branching pattern matched his own idea of descent with modification : We can see why characters derived from the embryo should be of equal importance with those derived from the adult, for a natural classification of course includes all ages.

Ernst Haeckel (1866), in his endeavour to produce a synthesis of Darwin's theory with Lamarckism and Naturphilosophie, proposed that "ontogeny recapitulates phylogeny," that is, the development of the embryo of every species (ontogeny) fully repeats the evolutionary development of that species (phylogeny), in Geoffroy's linear model rather than Darwin's idea of branching evolution. Haeckel's concept explained, for example, why humans, and indeed all vertebrates, have gill slits and tails early in embryonic development. His theory has since been discredited. However, it served as a backdrop for a renewed interest in the evolution of development after the modern evolutionary synthesis was established (roughly 1936 to 1947).

Stephen Jay Gould called this approach to explaining evolution as terminal addition; as if every evolutionary advance was added as new stage by reducing the duration of the older stages. The idea was based on observations of neoteny. This was extended by the more general idea of heterochrony (changes in timing of development) as a mechanism for evolutionary change.

D'Arcy Thompson postulated that differential growth rates could produce variations in form in his 1917 book On Growth and Form. He showed the underlying similarities in body plans and how geometric transformations could be used to explain the variations.

Edward B. Lewis discovered homeotic genes, rooting the emerging discipline of evo-devo in molecular genetics. In 2000, a special section of the Proceedings of the National Academy of Sciences (PNAS) was devoted to "evo-devo", and an entire 2005 issue of the Journal of Experimental Zoology Part B: Molecular and Developmental Evolution was devoted to the key evo-devo topics of evolutionary innovation and morphological novelty.

The developmental-genetic toolkit
The developmental-genetic toolkit consists of a small fraction of the genes in an organism's genome whose products control its development. These genes are highly conserved among Phyla. Differences in deployment of toolkit genes affect the body plan and the number, identity, and pattern of body parts. The majority of toolkit genes are components of signaling pathways, and encode for the production of transcription factors, cell adhesion proteins, cell surface receptor proteins, and secreted morphogens, all of these participate in defining the fate of undifferentiated cells, generating spatial and temporal patterns, which in turn form the body plan of the organism. Among the most important of the toolkit genes are those of the Hox gene cluster, or complex. Hox genes, transcription factors containing the more broadly distributed homeobox protein-binding DNA motif, function in patterning the body axis. Thus, by combinatorial specifying the identity of particular body regions, Hox genes determine where limbs and other body segments will grow in a developing embryo or larva. A paragon of a toolbox gene is Pax6/eyeless, which controls eye formation in all animals. It has been found to produce eyes in mice and Drosophila, even if mouse Pax6/eyeless was expressed in Drosophila.

This means that a big part of the morphological evolution undergone by organisms is a product of variation in the genetic toolkit, either by the genes changing their expression pattern or acquiring new functions. A good example of the first is the enlargement of the beak in Darwin's Large Ground-finch (Geospiza magnirostris), in which the gene BMP is responsible for the larger beak of this bird, relative to the other finches.

The loss of legs in snakes and other squamates is another good example of genes changing their expression pattern. In this case the gene Distal-less is very under-expressed, or not expressed at all, in the regions where limbs would form in other tetrapods. This same gene determines the spot pattern in butterfly wings, which shows that the toolbox genes can change their function.

Toolbox genes, as well as being highly conserved, also tend to evolve the same function convergently or in parallel. Classic examples of this are the already mentioned Distal-less gene, which is responsible for appendage formation in both tetrapods and insects, or, at a finer scale, the generation of wing patterns in the butterflies Heliconius erato and Heliconius melpomene. These butterflies are Müllerian mimics whose coloration pattern arose in different evolutionary events, but is controlled by the same genes. The previous supports Kirschner and Gerhardt's theory of Facilitated Variation, which states that morphological evolutionary novelty is generated by regulatory changes in various members of a large set of conserved mechanisms of development and physiology.

Development and the origin of novelty
Among the more surprising and, perhaps, counterintuitive (from a neo-Darwinian viewpoint) results of recent research in evolutionary developmental biology is that the diversity of body plans and morphology in organisms across many phyla are not necessarily reflected in diversity at the level of the sequences of genes, including those of the developmental genetic toolkit and other genes involved in development. Indeed, as Gerhart and Kirschner have noted, there is an apparent paradox: "where we most expect to find variation, we find conservation, a lack of change".

Even within a species, the occurrence of novel forms within a population does not generally correlate with levels of genetic variation sufficient to account for all morphological diversity. For example, there is significant variation in limb morphologies amongst salamanders and in differences in segment number in centipedes, even when the respective genetic variation is low.

A major question then, for evo-devo studies, is: If the morphological novelty we observe at the level of different clades is not always reflected in the genome, where does it come from? Apart from neo-Darwinian mechanisms such as mutation, translocation and duplication of genes, novelty may also arise by mutation-driven changes in gene regulation. The finding that much biodiversity is not due to differences in genes, but rather to alterations in gene regulation, has introduced an important new element into evolutionary theory. Diverse organisms may have highly conserved developmental genes, but highly divergent regulatory mechanisms for these genes. Changes in gene regulation are "second-order" effects of genes, resulting from the interaction and timing of activity of gene networks, as distinct from the functioning of the individual genes in the network.

The discovery of the homeotic Hox gene family in vertebrates in the 1980s allowed researchers in developmental biology to empirically assess the relative roles of gene duplication and gene regulation with respect to their importance in the evolution of morphological diversity. Several biologists, including Sean B. Carroll of the University of Wisconsin–Madison suggest that "changes in the cis-regulatory systems of genes" are more significant than "changes in gene number or protein function". These researchers argue that the combinatorial nature of transcriptional regulation allows a rich substrate for morphological diversity, since variations in the level, pattern, or timing of gene expression may provide more variation for natural selection to act upon than changes in the gene product alone.

Epigenetic alterations of gene regulation or phenotype generation that are subsequently consolidated by changes at the gene level constitute another class of mechanisms for evolutionary innovation. Epigenetic changes include modification of the genetic material due to methylation and other reversible chemical alteration, as well as nonprogrammed remolding of the organism by physical and other environmental effects due to the inherent plasticity of developmental mechanisms. The biologists Stuart A. Newman and Gerd B. Müller have suggested that organisms early in the history of multicellular life were more susceptible to this second category of epigenetic determination than are modern organisms, providing a basis for early macroevolutionary changes.