Evaluating the role of natural selection in the evolution of gene regulation

Surveys of gene expression reveal extensive variability both within and between a wide range of species. Compelling cases have been made for adaptive changes in gene regulation, but the proportion of expression divergence attributable to natural selection remains unclear. Distinguishing adaptive changes driven by positive selection from neutral divergence resulting from mutation and genetic drift is critical for understanding the evolution of gene expression. Here, we review the various methods that have been used to test for signs of selection in genomic expression data. We also discuss properties of regulatory systems relevant to neutral models of gene expression. Despite some potential caveats, published studies provide considerable evidence for adaptive changes in gene expression. Future challenges for studies of regulatory evolution will be to quantify the frequency of adaptive changes, identify the genetic basis of expression divergence and associate changes in gene expression with specific organismal phenotypes.