Journal Article

R2d2 Drives Selfish Sweeps in the House Mouse

Gabriel, Sofia I, Holt, James M, Hua, Kunjie, Yadgary, Liran, Bell, Timothy A, Britton-Davidian, Janice, Pomp, Daniel, Bult, Carol J, Jolley, Wesley J, Holmes, Andrew, Weinstock, George M, Yung-Hao, Ching, Grize, Sofia A, Rosshart, Stephan P, Thomas-Laemont, Patricia, McMullan, Rachel C, Giménez, Mabel D, Castiglia, Riccardo, Ventura, Jacint, Lindholm, Anna K, Campbell, Karl J, Morgan, Andrew P, Giagia-Athanasopoulou, Eva B, Searle, Jeremy B, Chunco, Amanda J, French, John E, Garland, Theodore, Fernando Pardo-Manuel de Villena, Mitsainas, George, Churchill, Gary A, ster, Daniel W, Hauffe, Heidi C, Gündüz, İslam, Maria da Graça Morgado Ramalhinho, Svenson, Karen L, da Luz Mathias, Maria, Crowley, James J, Solano, Emanuela, Meng-Shin, Shiao, Rehermann, Barbara, Chesler, Elissa J, Herman, Jeremy S, McMillan, Leonard, Gatti, Daniel M, López-Fuster, María J, Threadgill, David W, Didion, John P, Ortiz de Solorzano, Lydia

2016

Overview

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.

• Publisher: Oxford University Press
• Subject: Alleles / Chromosome 2 / Copy number / Evolutionary genetics / Genes / Genetic diversity / Genetic drift / Genetic variance / Litter size / Meiosis / Meiotic drive / Natural populations / Population genetics / Populations / Positive selection / Reproductive fitness