Natural Selection in Admixed Populations

项目总结 全球各地的人类种群都是由混合--以前分化的基因流--塑造的 组。以前不同的基因类型通过混合而突然结合，可以迅速改变等位基因 连锁不平衡的频率、杂合度和模式。这些工艺创造了新的材料 无论是积极的还是消极的选择都要采取行动，但也取决于 源种群。混合种群也为理解如何选择提供了强大的测试案例 一般的形状进化，因为混合种群中祖先模式的变化更容易 比较源群体中等位基因频率的变化，观察较短的时间尺度。尽管 混合物的普遍存在，目前推断选择的方法没有考虑混合物如何改变 选择的行动和它留下的遗传签名。检测选择的标准方法不起作用 在混合种群中；因为选择后混合通常发生在很短的时间尺度上，而混合- 等位基因频率和单倍型结构的诱导变化可能会掩盖经典的选择信号。匮乏 适当的方法限制了我们对疾病风险和人类进化的理解。此外，很少有研究 已经解决了重组如何通过改组单倍型来调节混合群体的选择 不同来源的种群，并影响有害变异的暴露。为了解决这些差距，这 该提案测试了两种重要的进化力量--积极选择和消极选择--如何塑造 混杂种群。该建议结合了方法开发和实证分析，以提供洞察力 混杂如何塑造多个混杂的非洲侨民的基本进化过程 人口。具体目标1将开发统计数据，通过以下方式检测混合种群中的阳性选择 利用当地的血统信息，结合混杂对单倍型结构的影响。这些新的 统计数据将被集成到开放获取软件中，并应用于在模拟和 代表不同人口统计情景的经验数据。《特定目标2》将测试外加剂如何结合 在源种群中发现的有害变异的明显分布。跟踪的频率 分离有害等位基因及其在纯合性运行中的成员将决定如何混合 而复合景观则调节了有害变异的暴露。描述了 混合种群及其来源种群中有害变异的动态变化将提供一个窗口 混合体如何改变遗传负荷。这一建议将推进自然资源研究的方法论。 混合群体中的选择，并阐明正选择和负选择如何形成混合群体的模式 研究不足的混合种群中的遗传变异和疾病风险。

PROJECT SUMMARY Human populations across the globe have been shaped by admixture--gene flow between previously diverging groups. The sudden combination of previously distinct genotypes through admixture can rapidly change allele frequencies, heterozygosity, and patterns of linkage-disequilibrium. These processes create new material for both positive and negative selection to act upon, but also depend on the independent adaptive histories of the source populations. Admixed populations also provide powerful test cases for understanding how selection shapes evolution in general, since changes in ancestry patterns in admixed populations are much easier to observe on short timescales compared to changes in allele frequencies in source populations. Despite the ubiquity of admixture, current methods for inferring selection do not consider how admixture changes the action of selection and the genetic signatures that it leaves. Standard methods to detect selection do not work in admixed populations; since selection post-admixture is often on a very short timescale, and admixture- induced shifts in allele frequencies and haplotype structure can obscure classic signals of selection. The lack of appropriate methods constrains our understanding of disease risk and human evolution. Further, few studies have addressed how recombination modulates selection in admixed populations by shuffling haplotypes from distinct source populations and influencing the exposure of deleterious variation. To address these gaps, this proposal tests how two important evolutionary forces--positive and negative selection--shape the genetics of admixed populations. This proposal combines methods development and empirical analyses to provide insight into how admixture shapes fundamental evolutionary processes in multiple admixed African diaspora populations. Specific Aim 1 will develop statistics to detect positive selection in admixed populations by leveraging local ancestry information to incorporate the effects of admixture on haplotype structure. These new statistics will be integrated into open-access software and applied to infer selection in both simulated and empirical data representing diverse demographic scenarios. Specific Aim 2 will test how admixture combines the distinct distributions of deleterious variation found in source populations. Tracking the frequencies of segregating deleterious alleles and their membership in runs-of-homozygosity will determine how admixture and the landscape of recombination modulate the exposure of deleterious variation. Characterizing the dynamics of deleterious variation in admixed populations and their source populations will provide a window into how admixture changes genetic load. This proposal will advance methodology for the study of natural selection in admixed populations and elucidate how both positive and negative selection shape patterns of genetic variation and disease risk in understudied admixed populations.