Selective Constraint on Noncoding Regions of Hominid Genomes

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Abstract
An important challenge for human evolutionary biology is to understand the genetic basis of human–chimpanzee differences. One influential idea holds that such differences depend, to a large extent, on adaptive changes in gene expression. An important step in assessing this hypothesis involves gaining a better understanding of selective constraint on noncoding regions of hominid genomes. In noncoding sequence, functional elements are frequently small and can be separated by large nonfunctional regions. For this reason, constraint in hominid genomes is likely to be patchy. Here we use conservation in more distantly related mammals and amniotes as a way of identifying small sequence windows that are likely to be functional. We find that putatively functional noncoding elements defined in this manner are subject to significant selective constraint in hominids. A major goal of human evolutionary biology is to understand what genetic changes make humans unique. One influential idea is that changes in gene expression are most responsible for unique human characteristics. Regulatory elements in noncoding DNA play a key role in controlling gene expression, so one approach is to study human–chimpanzee differences in these elements. Here we use conservation in more distantly related mammals and amniotes as a way of identifying small sequence windows that are likely to be functional. We find that putatively functional noncoding elements defined in this manner are subject to significant selective constraint in hominids. Contrary to some previous reports, these results argue that hominid noncoding regions are not evolving free of constraint.