Evolution of Primate Regulation

Gene Regulation in Primates Evolves under Tissue-Specific Selection Pressures:

Regulatory changes have long been hypothesized to play an important role in primate evolution. To identify adaptive regulatory changes in humans, we performed a genome-wide survey for genes in which regulation has likely evolved under natural selection. To do so, we used a multi-species microarray to measure gene expression levels in livers, kidneys, and hearts from six humans, chimpanzees, and rhesus macaques. This comparative gene expression data allowed us to identify a large number of genes, as well as specific pathways, whose inter-species expression profiles are consistent with the action of stabilizing or directional selection on gene regulation. Among the latter set, we found an enrichment of genes involved in metabolic pathways, consistent with the hypothesis that shifts in diet underlie many regulatory adaptations in humans. In addition, we found evidence for tissue-specific selection pressures, as well as lower rates of protein evolution for genes in which regulation evolves under natural selection. These observations are consistent with the notion that adaptive circumscribed changes in gene regulation have fewer deleterious pleiotropic effects compared with changes at the protein sequence level.

From table 3 of the paper, functional categories enriched among genes whose regulation are subject to selection. Just like with recent human evolution, food matters:

As can be seen, this network is enriched with transcription factors and genes with metabolic functions. The phenotypes that may be affected by the regulatory perturbation of this network include carbohydrate metabolism, lipid metabolism, and calcium signaling. Indeed, selection on metabolic related pathways, and in particular on calcium signaling, is particularly intriguing given the marked shift in diet that occurred during human evolution.

Also, this hint of particular evolutionary dynamics is intriguing:

Third, we found evidence for a correlation between both stabilizing and directional selection on gene regulation and evolutionary constraint at the protein sequence level (note that this result is inconsistent with our previous observation, which was based on a much smaller number of genes [11]). This observation suggests that adaptation at the regulatory level occurs disproportionably in genes that are widely constrained at the protein sequence level. In other words, our results support the hypothesis that adaptation through changes in evolutionary constrained genes can occur by altering their regulatory patterns.