R2d2 Drives Selfish Sweeps in the House Mouse
R2d2 Drives Selfish Sweeps in the House Mouse
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DOI：
10.1093/molbev/msw036
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发表时间：
2016-06-01
影响因子：
10.7
通讯作者：
de Villena, Fernando Pardo-Manuel
中科院分区：
文献类型：
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作者：
Didion, John P.;Morgan, Andrew P.;de Villena, Fernando Pardo-Manuel
选择性扫描是强正选择的结果，其驱使新出现的或存在的遗传变异固定，并且可以显著改变群体中等位基因多样性的模式和分布。群体水平的测序数据使人们能够发现与许多物种最近适应有关的基因的选择性扫描。相比之下，关于“自私”基因是否能够固定的争论很多，但证据很少，因此，尽管它们对生物体的适应性是中性的或有害的，但它们留下的特征与经典的选择性扫描相同。我们先前描述了R2d2，一个大拷贝数的变异，导致非随机分离的小鼠2号染色体在女性由于减数分裂驱动。在这里，我们展示了与自然种群中具有高拷贝数的R2d2等位基因（R2d2（HC））驱动的自私扫描一致的种群遗传数据。我们重复这一发现在多个封闭的育种群体从六个远交背景分离的R2d2等位基因。我们发现，R2d2（HC）的频率迅速增加，并在大多数情况下成为固定在显着更少的代比可以解释的遗传漂变。R2d2（HC）也与杂合子母亲的窝仔数显著减少相关，使其成为真正的自私等位基因。我们的数据提供了种群积极进行自私扫描的直接证据，并证明减数分裂驱动可以迅速改变基因组景观，有利于对整体达尔文适应性产生中性甚至负面影响的突变。进一步的研究将揭示自私清扫的发生率，并将阐明自私基因、适应和遗传漂变对进化的相对贡献。
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 (R2d2(HC)) in natural populations. We replicate this finding inmultiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) 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.