TY - JOUR T1 - R2d2 drives selfish sweeps in the house mouse JF - bioRxiv DO - 10.1101/024851 SP - 024851 AU - John P Didion AU - Andrew P Morgan AU - Liran Yadgary AU - Timothy A Bell AU - Rachel C McMullan AU - Lydia Ortiz de Solorzano AU - Janice Britton-Davidian AU - Carol J Bult AU - Karl J Campbell AU - Riccardo Castiglia AU - Yung-Hao Ching AU - Amanda J Chunco AU - James J Crowley AU - Elissa J Chesler AU - John E French AU - Sofia I Gabriel AU - Daniel M Gatti AU - Theodore Garland, Jr. AU - Eva B Giagia-Athanasopoulou AU - Mabel D Giménez AU - Sofia A Grize AU - Islam Gündüz AU - Andrew Holmes AU - Heidi C Hauffe AU - Jeremy S Herman AU - James M Holt AU - Kunjie Hua AU - Wesley J Jolley AU - Anna K Lindholm AU - María J López-Fuster AU - George Mitsainas AU - Maria da Luz Mathias AU - Leonard McMillan AU - M Graça Ramalhinho AU - Barbara Rehermann AU - Stephan P Rosshart AU - Jeremy B Searle AU - Meng-Shin Shiao AU - Emanuela Solano AU - Karen L Svenson AU - Pat Thomas-Laemont AU - David W Threadgill AU - Jacint Ventura AU - George M Weinstock AU - Daniel Pomp AU - Gary A Churchill AU - Fernando Pardo-Manuel de Villena Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/01/12/024851.abstract N2 - 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 empirical 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 non-random 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. ER -