Natural Selection Reduced Diversity on Human Y Chromosomes

The human Y chromosome exhibits surprisingly low levels of genetic diversity. This could result from neutral processes if the effective population size of males is reduced relative to females due to a higher variance in the number of offspring from males than from females. Alternatively, selection acting on new mutations, and affecting linked neutral sites, could reduce variability on the Y chromosome. Here, using genome-wide analyses of X, Y, autosomal and mitochondrial DNA, in combination with extensive population genetic simulations, we show that low observed Y chromosome variability is not consistent with a purely neutral model. Instead, we show that models of purifying selection are consistent with observed Y diversity. Further, the number of sites estimated to be under purifying selection greatly exceeds the number of Y-linked coding sites, suggesting the importance of the highly repetitive ampliconic regions. While we show that purifying selection removing deleterious mutations can explain the low diversity on the Y chromosome, we cannot exclude the possibility that positive selection acting on beneficial mutations could have also reduced diversity in linked neutral regions, and may have contributed to lowering human Y chromosome diversity. Because the functional significance of the ampliconic regions is poorly understood, our findings should motivate future research in this area.人类Y染色体的遗传多样性水平低得出人意料。若雄性后代数量的方差高于雌性，导致雄性有效种群规模相对雌性有所缩减，那么这种低多样性可能源于中性演化过程。另一方面，作用于新发突变并影响连锁中性位点的选择作用，也可能降低Y染色体的遗传变异性。本研究通过对X染色体、Y染色体、常染色体（autosomal）及线粒体DNA（mitochondrial DNA）开展全基因组分析，并结合大规模群体遗传模拟，证实观测到的Y染色体低变异性与纯中性演化模型并不相符。取而代之的是，本研究表明纯化选择（purifying selection）模型与观测到的Y染色体多样性相契合。进一步估算显示，受纯化选择作用的位点数量远超Y连锁编码位点的数量，这提示高度重复的扩增子区域（ampliconic regions）具有重要价值。尽管本研究证实，清除有害突变的纯化选择能够解释Y染色体的低多样性现象，但我们无法排除以下可能性：作用于有益突变的正向选择（positive selection）同样可能降低连锁中性区域的多样性，并可能对人类Y染色体多样性的降低起到了助推作用。鉴于扩增子区域的功能意义尚未得到充分阐明，本研究的发现将为该领域的后续研究提供有力的研究动力。