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Mentions: This dataset includes extensive ascertainment bias, both in the choice of genes studied and in the gene regions examined. Most researchers have focused on candidate genes. Even genome-wide mapping studies usually include a search for candidate genes in the mapped region, rather than functional surveys of all genes in the mapped region. But the most important consequence of investigator bias is that the relative number of coding versus cis-regulatory mutations causing phenotypic evolution is almost certainly inflated. Indeed, it is easier to identify potentially important coding changes, especially nonsense mutations, than potentially relevant changes in cis-regulatory regions by simple examination of the DNA sequence. The recent surge in examples of cis-regulatory evolution (Fig. 2) may be due to the fact that more powerful experimental approaches for identifying cis-regulatory mutations have been developed recently (e.g., McGregor et al. 2007).
The Loci of Evolution: How Predictable is Genetic Evolution?
Bottom Line: These patterns imply that the simple question "Do coding or cis-regulatory mutations cause more phenotypic evolution?" hides more interesting phenomena.Evolution in different kinds of populations and over different durations may result in selection of different kinds of mutations.Predicting the genetic basis of evolution requires a comprehensive synthesis of molecular developmental biology and population genetics.
Affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey 08544, USA. dstern@Princeton.edu
Abstract: Is genetic evolution predictable? Evolutionary developmental biologists have argued that, at least for morphological traits, the answer is a resounding yes. Most mutations causing morphological variation are expected to reside in the cis-regulatory, rather than the coding, regions of developmental genes. This "cis-regulatory hypothesis" has recently come under attack. In this review, we first describe and critique the arguments that have been proposed in support of the cis-regulatory hypothesis. We then test the empirical support for the cis-regulatory hypothesis with a comprehensive survey of mutations responsible for phenotypic evolution in multicellular organisms. Cis-regulatory mutations currently represent approximately 22% of 331 identified genetic changes although the number of cis-regulatory changes published annually is rapidly increasing. Above the species level, cis-regulatory mutations altering morphology are more common than coding changes. Also, above the species level cis-regulatory mutations predominate for genes not involved in terminal differentiation. These patterns imply that the simple question "Do coding or cis-regulatory mutations cause more phenotypic evolution?" hides more interesting phenomena. Evolution in different kinds of populations and over different durations may result in selection of different kinds of mutations. Predicting the genetic basis of evolution requires a comprehensive synthesis of molecular developmental biology and population genetics.
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