A selfish genetic element drives recurring selective sweeps in the house mouse

A selective sweep is the result of strong positive selection rapidly driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population or species. 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. Here we show that R2d2, a large copy-number variant that causes non-random segregation of mouse Chromosome 2 during female meiosis due to meiotic drive, has driven recurrent selective sweeps while having no discernable effect on fitness. We tested multiple closed breeding populations from six outbred backgrounds and found that alleles of R2d2 with high copy number (R2d2HC) rapidly increase in frequency, and in most cases become fixed in significantly fewer generations than can be explained by genetic drift. A survey of 13 natural mouse populations in Europe and the United States revealed that R2d2HC alleles are circulating at intermediate frequencies in the wild; moreover, patterns of local haplotype diversity are consistent with recent positive selection. Our results provide direct evidence of populations actively undergoing selective sweeps driven by a selfish genetic element, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effect on overall Darwinian fitness. Further study and updated models are required to clarify the relative contributions of selfish genes, adaptation and genetic drift to evolution.