R2d2Drives 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 (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.

World-wide distributions of lactase persistence alleles and the complex effects of recombination and selection

“…This asymmetry can be seen but was not commented on in previous work (Bersaglieri et al 2004 ). One could also speculate that a chromosomal rearrangement(s) might have assisted in driving the causative alleles to higher frequency, by transmission distortion similar to that found in other studies (Didion et al 2016 ; Odenthal-Hesse et al 2014 ). This might contribute to a more rapid increase in frequency and help to explain why the effect of selection seems so high for a phenotype whose selective advantage(s) are still somewhat elusive and environmentally variable (reviewed in Segurel and Bon 2017 ).…”

Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection

“…The allelic distortion on chromosome 2 was first detected in genotypes from generations G8 and G9, but by the time these data were analyzed, the G12 matings had been established and WSB/EiJ allele frequency had exceeded 0.60 (Didion et al 2016). Based on the observed rate of change, we determined that it was still possible to purge the WSB/EiJ allele at R2d2 while maintaining the essential characteristics of the DO population—random assortment and balanced allele frequencies—across the uninvolved regions of the genome.…”

Haploid selection, sex ratio bias, and transitions between sex-determining systems

“…Because both fisherian selection to equalise the sex ratio and the benefits of hitchhiking with driven alleles can facilitate transitions among sex chromosome systems, we predict that haploid selection should increase the lability of sex determination systems. Even in animal and plant species that have much larger and more conspicuous diploid phases than haploid phases, many loci have been shown to experience haploid selection through gamete competition and/or meiotic drive [ 38 – 41 , 51 – 56 ], which can generate biased sex ratios [ 57 – 64 ]. In animals, a relatively small proportion of all genes are thought to be expressed and selected during competition in animal sperm [ 39 , 65 , 66 ].…”