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

Abstract

AbstractBackgroundThe nucleotide composition of the genome is a balance between 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 among great ape species.ResultsWe report a stronger correlation between GC frequency and recombination for transitions than for transversions. Notably, CpG transitions are most strongly affected by gBGC. We show that the strength of gBGC differs for transitions and transversions but that its overall strength is positively correlated with effective population sizes of human populations and great ape species, with some notable exceptions, such as a stronger effect of gBGC on non-CpG transitions in populations of European descent. We 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 hypermutability of specific nucleotide contexts.ConclusionsDifferences in GC-biased gene conversion are evident between different mutation types, and dependent on sex-specific recombination, population size and flanking nucleotide context. Our results therefore highlight the importance of different gBGC dynamics experienced by GC-changing mutations and their impact on nucleotide composition evolution.