Population dynamics of GC-changing mutations in humans and great apes

Abstract

Abstract The nucleotide composition of the genome is a balance between the origin and fixation rates of different mutations. For example, it is well-known that transitions occur more frequently than transversions, particularly at CpG sites. Differences in fixation rates of mutation types are less explored. Specifically, recombination-associated GC-biased gene conversion (gBGC) may differentially impact GC-changing mutations, due to differences in their genomic distributions and efficiency of mismatch repair mechanisms. Given that recombination evolves rapidly across species, we explore gBGC of different mutation types across human populations and great ape species. We report a stronger correlation between segregating GC frequency and recombination for transitions than for transversions. Notably, CpG transitions are most strongly affected by gBGC in humans and chimpanzees. We show that the overall strength of gBGC is generally correlated with effective population sizes in humans, with some notable exceptions, such as a stronger effect of gBGC on non-CpG transitions in populations of European descent. Furthermore, species of the Gorilla and Pongo genus have a greatly reduced gBGC effect on CpG sites. We also study the dependence of gBGC dynamics on flanking nucleotides and show that some mutation types evolve in opposition to the gBGC expectation, likely due to the hypermutability of specific nucleotide contexts. Our results highlight the importance of different gBGC dynamics experienced by GC-changing mutations and their impact on nucleotide composition evolution.