RT Journal Article SR Electronic T1 R2d2 drives selfish sweeps in the house mouse JF bioRxiv FD Cold Spring Harbor Laboratory SP 024851 DO 10.1101/024851 A1 John P Didion A1 Andrew P Morgan A1 Liran Yadgary A1 Timothy A Bell A1 Rachel C McMullan A1 Lydia Ortiz de Solorzano A1 Janice Britton-Davidian A1 Carol J Bult A1 Karl J Campbell A1 Riccardo Castiglia A1 Yung-Hao Ching A1 Amanda J Chunco A1 James J Crowley A1 Elissa J Chesler A1 John E French A1 Sofia I Gabriel A1 Daniel M Gatti A1 Theodore Garland, Jr. A1 Eva B Giagia-Athanasopoulou A1 Mabel D Giménez A1 Sofia A Grize A1 Islam Gündüz A1 Andrew Holmes A1 Heidi C Hauffe A1 Jeremy S Herman A1 James M Holt A1 Kunjie Hua A1 Wesley J Jolley A1 Anna K Lindholm A1 María J López-Fuster A1 George Mitsainas A1 Maria da Luz Mathias A1 Leonard McMillan A1 M Graça Ramalhinho A1 Barbara Rehermann A1 Stephan P Rosshart A1 Jeremy B Searle A1 Meng-Shin Shiao A1 Emanuela Solano A1 Karen L Svenson A1 Pat Thomas-Laemont A1 David W Threadgill A1 Jacint Ventura A1 George M Weinstock A1 Daniel Pomp A1 Gary A Churchill A1 Fernando Pardo-Manuel de Villena YR 2016 UL http://biorxiv.org/content/early/2016/01/12/024851.abstract AB 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.