Natural Selection in Admixed Populations

混合种群中的自然选择

• 批准号: 10066510
• 负责人: Katharine Love Korunes
• 金额: $ 6.49万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10066510
• 关键词: Accounting; Address; Admixture; Affect; African; African American; Alleles; Americas; Computer software; Data; Evolution; Exposure to; Frequencies; Gene Exchanges; Gene Frequency; Genes; Genetic; Genetic Diseases; Genetic Load; Genetic Recombination; Genetic Variation; Genotype; Goals; Haplotypes; Health; Heterozygote; Human; Link; Linkage Disequilibrium; Malaria; Medical Genetics; Methodological Studies; Methods; Mutation; Natural Selections; Pattern; Phenotype; Population; Population Sizes; Prevalence; Process; Recording of previous events; Research; Running; Shapes; Signal Transduction; Source; Structure; Techniques; Testing; Training; Variant; Work; X Chromosome; autosome; density; disorder risk; expectation; genetic signature; genome-wide; genomic data; human data; insight; method development; migration; neglect; pressure; programs; statistics

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.

项目摘要 地球仪上的人类群体是由混合物--基因流--在先前不同的群体之间形成的 组先前不同的基因型通过混合物的突然组合可以迅速改变等位基因 频率、杂合性和连锁不平衡模式。这些过程创造了新的材料， 积极和消极的选择，但也取决于独立的适应历史， 源人口。混合种群也提供了强有力的测试案例，以了解选择是如何 一般来说，由于混合种群中祖先模式的变化更容易影响进化， 与来源人群中等位基因频率的变化相比，在短时间尺度上观察。尽管 由于混合物的普遍存在，目前用于推断选择的方法没有考虑混合物如何改变 选择的作用和它留下的遗传标记。检测选择的标准方法不起作用 在混合群体中;由于混合后的选择通常在很短的时间尺度上，并且混合物- 等位基因频率和单倍型结构的诱导变化可以掩盖选择的经典信号。缺乏 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 已经解决了如何重组调制选择混合人口改组单倍型从 不同的源种群和影响有害变异的暴露。为了弥补这些差距， 这项提案测试了两种重要的进化力量--积极选择和消极选择--是如何塑造人类基因的。 混合种群该建议结合了方法开发和实证分析， 混合物如何塑造多个非洲移民的基本进化过程 人口。具体目标1将开发统计数据，以检测混合群体中的阳性选择， 利用当地的祖先信息来合并混合物对单倍型结构的影响。这些新 统计数据将被集成到开放获取软件中，并应用于推断模拟和 代表不同人口情景的经验数据。具体目标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中的成员资格将决定混合物如何 重组的景观调节了有害变异的暴露。表征 混合种群及其源种群中有害变异的动态将提供一个窗口 混合物如何改变基因负荷这一建议将推进自然科学研究的方法学。 选择混合种群，并阐明如何积极和消极的选择形状模式， 遗传变异和疾病风险在研究不足的混合人群。