Evolution of DNA Methylation in Papio Baboons.

Tauras P Vilgalys,Jenny Tung,Clifford J Jolly,Jeffrey Rogers,Baboon Genome Analysis Baboon Genome Analysis,Sayan Mukherjee,Connie Mulligan

doi:10.1093/molbev/msy227

Tauras P Vilgalys, Jenny Tung + Show 5 more

Open Access

https://doi.org/10.1093/molbev/msy227

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Abstract

Changes in gene regulation have long been thought to play an important role in primate evolution. However, although a number of studies have compared genome-wide gene expression patterns across primate species, fewer have investigated the gene regulatory mechanisms that underlie such patterns, or the relative contribution of drift versus selection. Here, we profiled genome-scale DNA methylation levels in blood samples from five of the six extant species of the baboon genus Papio (4-14 individuals per species). This radiation presents the opportunity to investigate DNA methylation divergence at both shallow and deeper timescales (0.380-1.4 My). In contrast to studies in human populations, but similar to studies in great apes, DNA methylation profiles clearly mirror genetic and geographic structure. Divergence in DNA methylation proceeds fastest in unannotated regions of the genome and slowest in regions of the genome that are likely more constrained at the sequence level (e.g., gene exons). Both heuristic approaches and Ornstein-Uhlenbeck models suggest that DNA methylation levels at a small set of sites have been affected by positive selection, and that this class is enriched in functionally relevant contexts, including promoters, enhancers, and CpG islands. Our results thus indicate that the rate and distribution of DNA methylation changes across the genome largely mirror genetic structure. However, at some CpG sites, DNA methylation levels themselves may have been a target of positive selection, pointing to loci that could be important in connecting sequence variation to fitness-related traits.

Highlights

Changes in gene regulation have long been hypothesized to play an important role in trait evolution (Britten and Davidson 1971; King and Wilson 1975; Jacob 1977; Wray 2007; Stern and Orgogozo 2008)
The number of shifts per species was not a function of sample size or independent evolutionary time. We identified another set of 9,803 CpG sites with evidence for a clade-specific shift: 2,843 sites where DNA methylation in the northern clade was different from the southern clade species and macaques, 5,340 sites where DNA methylation in the southern clade was different from the northern clade species and macaques, and 1,640 sites where methylation differed between the two clades and both clades were different from macaques
Our results indicate that DNA methylation in functionally important regions of the genome evolves more slowly than DNA methylation in unannotated regions, consistent with stabilizing selection on gene regulation and neutral evolution for functionally silent CpG sites

Summary

Introduction

Changes in gene regulation have long been hypothesized to play an important role in trait evolution (Britten and Davidson 1971; King and Wilson 1975; Jacob 1977; Wray 2007; Stern and Orgogozo 2008). Regulatory changes have the potential to be more modular, and more specific to the individual tissues, environmental conditions, or developmental time points targeted by selection, than protein-coding changes (Stern 2000). In support of the importance of regulatory evolution, a number of studies have identified regulatory changes that contribute to species-specific adaptations. Non-coding variants that regulate the ectodysplasin and pitx genes underlie morphological changes that separate saltwater threespine sticklebacks (Gasterosteus aculeatus) from their close freshwater relatives (Colosimo, et al 2004; Shapiro, et al 2004; Colosimo, et al 2005).

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