title: R2d2 Drives Selfish Sweeps in the House Mouse.
abstract: 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. R2d2(HC) 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.
authors.affiliation: Department of Genetics, The University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill Carolina Center for Genome Science, The University of North Carolina at Chapel Hill fernando@med.unc.edu.
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authors.affiliation: Department of Genetics, The University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill Carolina Center for Genome Science, The University of North Carolina at Chapel Hill.
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authors.affiliation: Department of Genetics, The University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill Carolina Center for Genome Science, The University of North Carolina at Chapel Hill.
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authors.affiliation: Department of Genetics, The University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill Carolina Center for Genome Science, The University of North Carolina at Chapel Hill.
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mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000483:Alleles; D000818:Animals; D005075:Biological Evolution; D056915:DNA Copy Number Variations / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D005828:Genetics, Population; D008297:Male; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D012641:Selection, Genetic
chemical_list: C000607845:CWC22 protein, mouse; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins
keywords: House Mouse.; Meiotic Drive; R2d2; Selective Sweep; Selfish Genes