Increased positive selection in highly recombining genes does not necessarily reflect an evolutionary advantage of recombination

Abstract

It is commonly thought that the long-term advantage of meiotic recombination is to dissipate genetic linkage, allowing natural selection to act independently on different loci. It is thus theoretically expected that genes with higher recombination rates evolve under more effective selection, and can adapt more easily to environmental change. On the other hand, recombination is often associated with GC-biased gene conversion (gBGC), which theoretically interferes with selection by promoting the fixation of deleterious GC alleles. To test these predictions, several empirical studies assessed whether selection was more effective in highly recombining genes (due to dissipation of genetic linkage) or less effective (due to gBGC), implicitly assuming a fixed distribution of fitness effects (DFE) for all genes. In this study, I directly derive the expected shape of the DFE from the evolutionary history of a gene (shaped by mutation, selection, drift and gBGC) under empirical fitness landscapes. I show that genes that have known high levels of gBGC are less fit and thus have more opportunities for beneficial mutations. Only a slight decrease in the genome-wide intensity of gBGC leads to the fixation of these beneficial mutations, particularly in highly recombining genes. This shows that increased positive selection in highly recombining genes is not by itself an evidence for more effective selection due to the dissipation of genetic linkage. Additionally, I show that the death of a long-lived recombination hotspot can lead to a higherdN/dSthan its birth, but with substitutions patterns biased towards AT, and only at selected position. This shows that controlling for a substitution bias towards GC is therefore not sufficient to rule out the contribution of gBGC to signatures of accelerated evolution.