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

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 recessive deleterious mutations in repulsion mimic overdominance. Pseudo-overdominance arises when linkage disequilibrium gradually builds up between recessive deleterious mutations, often due to strong genetic linkage and genetic drift. Once complementary haplotypes form, homozygous and recombinant offspring are selected against because they carry homozygous recessive deleterious mutations. Using individual-based simulations, we demonstrate here that the presence of loci under balancing selection eases the establishment of pseudo-overdominance, by facilitating the maintenance of recessive deleterious mutations and linkage disequilibrium in their flanking regions. We further show that, under some conditions, such resulting pseudo-overdominant zones can ultimately lead to selection for crossing-over 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 and supergenes, and shed new light on mechanisms driving genome evolution.