Protein response to deleterious episodes of GC-biased gene conversion in mammals of different Ne

Abstract

GC-biased gene conversion (gBGC) is a widespread recombination-associated process that favours the fixation of GC alleles independently of their fitness. In coding regions, it can oppose purifying selection and favour the accumulation of deleterious AT to GC mutations. In mammals where recombination hotspots are predominantly determined by PRDM9, the deleterious effect of gBGC is expected to be episodic due to the rapid turnover of hotspots. The deleterious impact of gBGC episodes on proteins has been well documented, particularly in rodents and primates. However, the evolutionary response of the affected proteins after the episodes end has been scarcely investigated. Theory predicts that a decline in gBGC intensity should trigger a compensatory response that enables previous damage to be repaired. Recently, we reported evidence for pervasive compensatory evolution following gBGC episodes in Hydromyini rodents. Here, we aimed to investigate whether this post- gBGC compensation is widespread among mammals in which gBGC is episodic. Using a phylogenetic approach, we analysed substitution patterns in coding exons from five mammalian taxa spanning a range of effective population size (Ne): Murini, Rattini, Cetacea, Cercopithecidae and Hominoidae. We detected thousands of gBGC episodes, characterised by an increased rate of non-synonymous AT to GC substitutions. We found evidence for compensatory evolution in non-primate taxa, and a lack of signal in Primates. Although the influence of Ne remains unclear, our study highlights both the evolutionary significance of post-gBGC compensation and the methodological challenges in detecting it.