Loci under balancing selection facilitate the emergence of pseudo-overdominance and recombination suppression

Abstract

Loci under strong balancing selection, such as sex-determining, mating-type, and self-incompatibility loci, are frequently flanked by regions of suppressed recombination. The reasons why recombination suppression evolves around these loci remain poorly understood. Here, we propose that one reason may be that loci under balancing selection facilitate the emergence of pseudo-overdominance, a phenomenon under which linked partially recessive deleterious mutations in repulsion mimic overdominance. Pseudo-overdominance arises under certain conditions when linkage disequilibrium gradually builds up between recessive deleterious mutations, often due to strong genetic linkage and genetic drift, forming complementary haplotypes. Homozygous and recombinant offspring are then selected against because they carry homozygous recessive deleterious mutations. Using individual-based simulations, we demonstrate here that the presence of loci under balancing selection (overdominant) eases the establishment of pseudo-overdominance by facilitating the maintenance of partially recessive deleterious mutations and linkage disequilibrium in their flanking regions. This occurs particularly in regions with low recombination rates and a high load of partially recessive deleterious mutations, which can be found in specific genomic regions in natural populations. We additionally show that selfing, while generally hindering pseudo-overdominance establishment, can in contrast facilitate its establishment around a permanently heterozygous locus, likely because recessive deleterious mutations are protected from being purged near such a locus and selfing increases genetic drift. Once established, we further showed that pseudo-overdominance can in turn favor the evolution of recombination suppression around permanently heterozygous loci, preventing the creation of unfit homozygous recombinant offspring. These results suggest new avenues for understanding the evolution of loci under balancing selection, sex chromosomes, mating-type chromosomes in selfing fungi, supergenes, and shed new light on the mechanisms driving genome evolution.