Selective constraint on noncoding regions of hominid genomes

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.

Figure 1. Levels of Human–Chimpanzee Divergence for Different Conservation Scores

Conservation scores are calculated using either human–mouse–dog three-way comparisons (A) or human–mouse–chicken comparisons (B). Error bars represent 95% confidence intervals.

Figure 2. Levels of Mouse–Rat Divergence for Different Conservation Scores

Conservation scores are calculated using human–mouse–dog three-way comparisons (A) or human–mouse–chicken comparisons (B). Error bars represent 95% confidence intervals.

Figure 3. Human–Chimpanzee Divergence in 500-bp Blocks over Our 10-kb Upstream Noncoding Sequences

Y axis range is the same as in Figure 1.