Perspective: Evolutionary developmental biology and the problem of variation

One of the oldest problems in evolutionary biology remains largely unsolved . Which mutations generate evolutionarily relevant phenotypic variation? Wh at kinds of molecular changes do they entail? What are the phenotypic magni tudes, frequencies of origin, and pleiotropic effects of such mutations? Ho w is the genome constructed to allow the observed abundance of phenotypic d iversity? Historically, the neo-Darwinian synthesizers stressed the predomi nance of micromutations in evolution, whereas others noted the similarities between some dramatic mutations and evolutionary transitions to argue for macromutationism. Arguments on both sides have been biased by misconception s of the developmental effects of mutations. For example, the traditional v iew that mutations of important developmental genes always have large pleio tropic effects can now be seen to be a conclusion drawn from observations o f a small class of mutations with dramatic effects. It is possible that som e mutations, for example, those in cis-regulatory DNA, have few or no pleio tropic effects and may be the predominant source of morphological evolution . In contrast, mutations causing dramatic phenotypic effects, although supe rficially similar to hypothesized evolutionary transitions, are unlikely to fairly represent the true path of evolution. Recent developmental studies of gene function provide a new way of conceptualizing and studying variatio n that contrasts with the traditional genetic view that was incorporated in to neo-Darwinian theory and population genetics. This new approach in devel opmental biology is as important for microevolutionary studies as the actua l results from recent evolutionary developmental studies. In particular, th is approach will assist in the task of identifying the specific mutations g enerating phenotypic variation and elucidating how they alter gene function . These data will provide the current missing link between molecular and ph enotypic variation in natural populations.