The fate of recessive deleterious or overdominant mutations near mating-type loci under partial selfing

Abstract

Large regions of suppressed recombination having extended over time occur in many organisms around genes involved in mating compatibility (sex-determining or mating-type genes). The sheltering of deleterious alleles has been proposed to be involved in such expansions. However, the dynamics of deleterious mutations partially linked to genes involved in mating compatibility are not well understood, especially in finite populations. In particular, under what conditions deleterious mutations are likely to be maintained for long enough near mating-compatibility genes remains to be evaluated, especially under selfing, which generally increases the purging rate of deleterious mutations. Using a branching process approximation, we studied the fate of a new deleterious or overdominant mutation in a diploid population, considering a locus carrying two permanently heterozygous mating-type alleles, and a partially linked locus at which the mutation appears. We obtained analytical and numerical results on the probability and purging time of the new mutation. We investigated the impact of recombination between the two loci and of the mating system (outcrossing, intra and inter-tetrad selfing) on the maintenance of the mutation. We found that the presence of a fungal-like mating-type locus (i.e. not preventing diploid selfing) always sheltered the mutation under selfing, i.e. it decreased the purging probability and increased the purging time of the mutations. The sheltering effect was higher in case of automixis (intra-tetrad selfing). This may contribute to explain why evolutionary strata of recombination suppression near the mating-type locus are found mostly in automictic (pseudo-homothallic) fungi. We also showed that rare events of deleterious mutation maintenance during strikingly long evolutionary times could occur, suggesting that deleterious mutations can indeed accumulate near the mating-type locus over evolutionary time scales. In conclusion, our results show that, although selfing purges deleterious mutations, these mutations can be maintained for very long times near a mating-type locus, which may contribute to promote the evolution of recombination suppression in sex-related chromosomes.

Can mechanistic constraints on recombination reestablishment explain the long-term maintenance of degenerate sex chromosomes?

“…Investigating whether DC always evolves, at least for dosage-sensitive genes, for old degenerate sex chromosomes would also be interesting, to confirm the key role of DC in their long-term stability. Several cases of interest should be investigated further, notably cases involving non-random mating (Charlesworth & Wall, 1999;Olito et al, 2022;Tezenas et al, 2023) or UV and mating-type chromosomes. Analytical models are needed to generalize the recent findings that have mostly been explored by simulation.…”

Can mechanistic constraints on recombination reestablishment explain the long-term maintenance of degenerate sex chromosomes?

“…While the widespread occurrence of DC [72,73] indicates that it is needed at least for some genes, it would be interesting to introduce heterogeneity among genes in selection on dosage, and varying the genetic architecture of DC (local vs global). Several cases of interest should be investigated further, notably cases involving non-random mating [18,29,74] or UV and mating-type chromosomes. Analytical models are needed to generalize the recent findings that have mostly been explored by simulation.…”

“…Investigating whether DC always evolves, at least for dosage-sensitive genes, for old degenerate sex chromosomes would also be interesting, to confirm the key role of DC in their long-term stability. Several cases of interest should be investigated further, notably cases involving non-random mating [18,29,82] or UV and mating-type chromosomes. Analytical models are needed to generalize the recent findings that have mostly been explored by simulation.…”

Long-Term Balancing Selection and the Genetic Load Linked to the Self-Incompatibility Locus in Arabidopsis halleri and A. lyrata

“…The deterministic model by Leach et al (1986) showed that very tight linkage is required for effective sheltering of lethal recessive mutations. More recently, Tezenas et al (2023) predicted using analytical and numerical modeling that even though the deleterious mutations partially linked to a fungal-like mating-type locus (where two alleles segregate as nonrecombining haplotypes) are almost surely purged, a limited fraction of them may persist for extended periods of time. Charlesworth et al (1997) showed that sites linked to a locus under balancing selection evolve in a manner that is analogous to a geographically subdivided population, where each of the balanced allelic line has a small effective population size, and mildly deleterious linked mutations can rise to intermediate or high frequencies within them by genetic drift.…”