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

GC-biased gene conversion (gBGC) is a recombination process that favors the preservation of GC alleles, irrespective of their fitness. In coding regions, this mechanism can counteract purifying selection and promote the accumulation of harmful AT to GC mutations. In mammals, where recombination hotspots are primarily governed by PRDM9, the detrimental effect of gBGC is anticipated to be intermittent, owing to the quick turnover of hotspots.

The harmful consequences of gBGC episodes on proteins have been extensively documented, especially in rodents and primates. Nonetheless, the evolutionary reaction of the affected proteins post-episodes has received minimal attention.

Research suggests that a reduction in gBGC intensity should prompt a compensatory response, enabling the restoration of damaged proteins. We recently observed evidence of widespread compensatory evolution following gBGC episodes in Hydromyini rodents. This study aims to explore whether such post-gBGC compensation is a common occurrence across various mammals experiencing episodic gBGC.

By employing a phylogenetic approach, we examined substitution patterns in coding exons from five mammalian lineages with varying effective population sizes (Ne): Murini, Rattini, Cetacea, Cercopithecidae, and Hominoidae. Our analysis revealed thousands of gBGC episodes, distinguished by an elevated rate of non-synonymous AT to GC substitutions.

We identified evidence of compensatory evolution in non-primate taxa, but observed no significant signal in Primates. Although the impact of Ne remains uncertain, this investigation underscores the evolutionary importance of post-gBGC compensation and the methodological difficulties in uncovering it.