Evolution of Gene Regulation in Papio Baboons

Changes in gene regulation are thought to play an important role in primate evolution and divergence. In support of this hypothesis, comparative evidence clearly demonstrate that gene expression patterns differ between closely related species and tend to evolve under selective constraint. However, we know little about the evolutionary forces that shape gene regulation across primates, particularly outside of humans and the other great apes. To address this gap, my dissertation draws on population and functional genomic variation between baboon species and within an admixed wild baboon population to address two themes: (i) how is gene regulatory divergence related to genetic divergence? and (ii) to what extent has natural selection shaped regulatory variation? Using interspecific comparative approaches, I show that changes in DNA methylation accumulate with increasing sequence divergence. While most changes in methylation can be explained by genetic drift, a subset are likely to have evolved under positive selection. Then, using genomic data from admixed baboons, I show that interspecific changes in DNA methylation are linked to genetic effects on DNA methylation (i.e., methylation quantitative trait loci, meQTL) and differences in allele frequency between baboon species. I also show that changes in DNA methylation are associated with changes in gene expression. Finally, I identify genomic evidence for selection against admixture in baboons, especially near genes that are differentially expressed between species. Together, my work highlights the close relationship between genetic and gene regulatory divergence in baboons. It also emphasizes the importance of natural selection in shaping genetic and regulatory variation throughout primate evolution, including in a living model for admixture in our own lineage.