Sheltering of deleterious mutations explains the stepwise extension of recombination suppression on sex chromosomes and other supergenes

Abstract

Many organisms have sex chromosomes with large nonrecombining regions that have expanded stepwise, generating “evolutionary strata” of differentiation. The reasons for this remain poorly understood, but the principal hypotheses proposed to date are based on antagonistic selection due to differences between sexes. However, it has proved difficult to obtain empirical evidence of a role for sexually antagonistic selection in extending recombination suppression, and antagonistic selection has been shown to be unlikely to account for the evolutionary strata observed on fungal mating-type chromosomes. We show here, by mathematical modeling and stochastic simulation, that recombination suppression on sex chromosomes and around supergenes can expand under a wide range of parameter values simply because it shelters recessive deleterious mutations, which are ubiquitous in genomes. Permanently heterozygous alleles, such as the male-determining allele in XY systems, protect linked chromosomal inversions against the expression of their recessive mutation load, leading to the successive accumulation of inversions around these alleles without antagonistic selection. Similar results were obtained with models assuming recombination-suppressing mechanisms other than chromosomal inversions and for supergenes other than sex chromosomes, including those without XY-like asymmetry, such as fungal mating-type chromosomes. However, inversions capturing a permanently heterozygous allele were found to be less likely to spread when the mutation load segregating in populations was lower (e.g., under large effective population sizes or low mutation rates). This may explain why sex chromosomes remain homomorphic in some organisms but are highly divergent in others. Here, we model a simple and testable hypothesis explaining the stepwise extensions of recombination suppression on sex chromosomes, mating-type chromosomes, and supergenes in general.

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

“…In particular, if linkage is complete (corresponding to r = 0 here, or to the case where the inversion encompasses a permanently heterozygous locus in Jay et al, 2022), an overdominant allele may be maintained in a population and even sweep to fixation with non-zero probability, which confirms previous findings (Antonovics et al, 1998, Antonovics and Abrams, 2004, Jay et al, 2022). This means that, although selfing purges deleterious mutations, a mating-type locus can have a sheltering effect in its flanking regions.…”

“…In conclusion, our findings show that a mating-type locus has a sheltering effect on nearby deleterious mutations, especially in case of selfing and automixis, which can then play a role in the evolution of recombination suppression near mating-compatibility loci (Antonovics and Abrams, 2004, Jay et al, 2022). This may contribute to explain why evolutionary strata of recombination suppression near the mating-type locus are found mostly in automictic (pseudo-homothalic) fungi (Menkis et al, 2008, Branco et al, 2017, Branco et al, 2018, Hartmann et al, 2020, Hartmann, Ament-Velásquez, et al, 2021, Foulongne-Oriol et al, 2021, Vittorelli et al, 2022).…”

“…The question addressed here on the accumulation of deleterious mutations applies, beyond mating-type loci, to other regions around permanently heterozygous alleles and with suppressed recombination, such as supergenes or self-incompatibility loci (Llaurens et al, 2017). The diversity of observed patterns regarding the presence or absence, length and number of evolutionary strata around these regions (Uyenoyama, 2005) may be explained, in addition to the mating system, by other factors controlling the long-term behavior of deleterious mutations and not studied here, such as the number of alleles at supergenes, the length of the haploid phase (Jay et al, 2022), and the presence of multiple load loci, possibly physically linked and with epistatic interactions (Abu Awad and Roze, 2018, Lenormand and Roze, 2022).…”

Dynamics of transposable element accumulation in the non-recombining regions of mating-type chromosomes in anther-smut fungi

“…TEs can, in particular, promote chromosomal rearrangements by TE-mediated ectopic recombination, including inversions at the margin of non-recombining regions (Ironside, 2010). TE-induced loss-of-function mutations constitute recessive deleterious mutations in the recombining regions adjacent to the non-recombining zone, called pseudo-autosomal regions, which can select for extending the region of recombination suppression that shelters this genetic load (Jay et al, 2022). TE silencing epigenetic modifications, such as DNA methylation and heterochromatin formation, can in themselves block recombination (Maloisel & Rossignol, 1998;Ben-Aroya et al, 2004;Yelina et al, 2012Yelina et al, , 2015Bachtrog, 2013;Li et al, 2016).…”

Chromosome-scale reference genome and RAD-based genetic map of yellow starthistle (Centaurea solstitialis) reveal putative structural variation and QTLs associated with invader traits

“…Balancing selection on overdominant inversions is a classic form of local adaptation in general (Faria et al, 2019), making this QTL a particularly intriguing candidate for local adaptation in this system. Alternatively, overdominance at this QTL could be explained by heterozygous loci across the inversion masking deleterious alleles (Connallon & Olito, 2022; Jay et al, 2022), which are likely to accumulate during biological invasions due to strong genetic drift (i.e. expansion load: Gilbert et al, 2017; Peischl et al, 2015).…”