A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2 HC ) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2 HC rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2HC is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution.

A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether “selfish” genes are capable of fixation—thereby leaving signatures identical to classical selective sweeps—despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2HC) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2HC rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2HC is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution.

BackgroundWestern house mice Mus musculus domesticus are among the most important mammalian model species for chromosomal speciation. Hybrids between chromosomal races of M. m. domesticus suffer various degrees of fertility reduction between full fertility and complete sterility, depending on the complexity of the chromosomal differences between the races. This complexity presents itself in hybrids as meiotic configurations of chromosome chains and rings, with longer configurations having a stronger impact on fertility. While hybrids with short configurations have been intensively studied, less work has been done on hybrids with very long configurations. In this study, we investigated laboratory-reared wild mice from two chromosomally very different races in Switzerland found in close proximity. Hybrids between these races form a meiotic chain of fifteen chromosomes. We performed a detailed analysis of male and female hybrid fertility, including three generations of female backcrosses to one of the parental races. We also tested for possible divergence of mate preference in females.ResultsWhile all male F1 hybrids were sterile with sperm counts of zero, 48% of female F1 hybrids produced offspring. Their litter sizes ranged from one to three which is significantly lower than the litter size of parental race females. When hybrid females were backcrossed to a parental race, half of the offspring resembled the parental race in karyotype and fertility, while the other half resembled the F1 hybrids. In the preference test, females of both races indicated a lack of a preference for males of their own karyotype.ConclusionsAlthough the fertility of the F1 hybrids was extremely low because of the complexity of the chromosomal differences between the races, reproductive isolation was not complete. As we did not find assortative female preferences, we expect that contact between these races would lead to the production of hybrids and that gene flow would occur eventually, as fertility can be restored fully after one backcross generation.Electronic supplementary materialThe online version of this article (10.1186/s12862-018-1322-y) contains supplementary material, which is available to authorized users.

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