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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.

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.

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 (\\textit{i.e.} not preventing diploid selfing) always sheltered the mutation under selfing, \\textit{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.Competing Interest StatementThe authors have declared no competing interest.Footnotes* Link to the PCI recommendation added on the front page. Otherwise, the manuscript is the same as version 2.* https://github.com/EmilieTezenas/Mutations_near_mating_type* https://zenodo.org/badge/latestdoi/542507441

Many organisms have sex chromosomes with large non-recombining 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. There may, therefore, be other mechanisms involved in the extension of non-recombining regions. We show here, by mathematical modeling and stochastic simulation, that recombination suppression on sex chromosomes and around supergenes can expand in a stepwise manner 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 the need for 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 was lower (e.g. under conditions of large effective population size, low mutation rates and high dominance coefficients). This may explain why sex chromosomes remain homomorphic in some organisms but are highly divergent in others. Here, we explicitly state and model a simple and testable hypothesis explaining the existence of stepwise extensions of recombination suppression on sex chromosomes, which can also be applied to mating-type chromosomes and supergenes in general. Competing Interest Statement The authors have declared no competing interest.

Kidney transplant recipients develop atypical infections in their epidemiology, presentation and outcome. Among these, meningitis and meningoencephalitis require urgent and adapted anti-infectious therapy, but published data is scarce in KTRs. The aim of this study was to describe their epidemiology, presentation and outcome, in order to improve their diagnostic and management. We performed a retrospective, multicentric cohort study in 15 French hospitals that included all 199 cases of M/ME in KTRs between 2007 and 2018 (0.9 case per 1,000 KTRs annually). Epidemiology was different from that in the general population: 20% were due to Cryptococcus neoformans , 13.5% to varicella-zoster virus, 5.5% to Mycobacterium tuberculosis , and 4.5% to Enterobacteria (half of which produced extended spectrum beta-lactamases), and 5% were Post Transplant Lymphoproliferative Disorders. Microorganisms causing M/ME in the general population were infrequent (2%, for Streptococcus pneumoniae ) or absent ( Neisseria meningitidis ). M/ME caused by Enterobacteria, Staphylococci or filamentous fungi were associated with high and early mortality (50%–70% at 1 year). Graft survival was not associated with the etiology of M/ME, nor was impacted by immunosuppression reduction. Based on these results, we suggest international studies to adapt guidelines in order to improve the diagnosis and the probabilistic treatment of M/ME in SOTRs.