Admixture influences the genetic architecture of DNA methylation in a wild primate hybrid zone

Hybrid zones play a central role in evolutionary biology because they serve as natural laboratories for studying how traits and taxa diverge. Changes in gene regulation make important contributions to this process. However, the degree to which admixture shapes gene regulatory variation in hybrid populations remains poorly understood. Here, we combine genome-wide resequencing and DNA methylation data from 295 hybrid baboons-members of a single, intensively studied natural population-to investigate how admixture affects the genetic architecture of this important epigenetic mark.

We find that local genetic ancestry frequently predicts DNA methylation levels and recapitulates differences between the parent species. By performing methylation quantitative trait locus mapping, we show that these differences predominantly arise due to evolved differences in allele frequencies. Thus, admixture in the hybrid population increases variance in DNA methylation, including by introducing genetic variants affecting DNA methylation that would otherwise be invariant. Finally, we integrate massively parallel reporter assay data to show that admixture-derived variation in DNA methylation alters enhancer activity and gene expression.

Together, these results demonstrate how admixture can meaningfully alter the genetic architecture of gene regulatory traits in natural hybrid zones. They also suggest that the genetic architecture of DNA methylation is conserved across closely related primates, suggesting that genetic effects on gene regulation may remain stable over timescales that range into the millions of years.