Evolution of GC-biased gene conversion by natural selection

GC-biased gene conversion is a recombination-associated evolutionary process that biases the segregation ratio of AT:GC polymorphisms in the gametes of heterozygotes, in favor of GC alleles. This process is the major determinant of the variation in base composition across the human genome and can be the cause of a substantial burden of deleterious GC alleles. While the importance of GC-biased gene conversion in molecular evolution is increasingly recognized, the reasons for its existence and its variation in intensity between species remain largely unknown. Using simulations and semi-analytical approximations, we investigated the evolution of GC-biased gene conversion as a quantitative trait evolving by mutation, drift, and natural selection. We show that in a finite population in which most mutations are deleterious, GC-biased gene conversion is under weak stabilizing selection around a positive value that mainly depends on the intensity of the mutational bias and on the selective constraints exerted on the genome. Importantly, the levels of GC-biased gene conversion that evolve by natural selection do not minimize the load in the population and even increase it substantially in regions of high recombination rate. Therefore, even if they reduce the fitness of the population, the levels of GC-biased gene conversion currently observed in humans may, in fact, have been (weakly) positively selected.