Natural Selection in Admixed Populations

混合种群中的自然选择

• 批准号: 10212352
• 负责人: Katharine Love Korunes
• 金额: $ 4.88万
• 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 2022-03-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10212352
• 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 全球的人类种群是由混合物形成的 - 先前分歧之间的流动 组。以前不同基因型通过混合的突然组合可以迅速改变等位基因 频率，杂合性和连锁区的模式。这些过程为 积极和负面选择要采取行动，但也取决于独立的自适应历史 来源人群。混合人群还提供了强大的测试案例，以了解选择 通常，形状的演变，因为混合种群中的祖先模式的变化要容易得多 与源群体中等位基因频率的变化相比，在短时间内观察。尽管有 混合物的普遍性，当前推断选择的方法没有考虑混合物如何改变 选择的作用及其留下的遗传特征。检测选择的标准方法不起作用 在混合人群中；由于选择后的选择通常在很短的时间范围内，并且混合 - 诱导的等位基因频率和单倍型结构的转移会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 已经解决了重组如何通过从中调制混合种群中的选择 不同的来源人群并影响有害变化的暴露。为了解决这些差距，这个 提案测试两个重要的进化力如何阳性和负选择 - 形状的遗传学 混合种群。该建议结合了方法的开发和经验分析以提供洞察力 在多个混合非洲侨民中的混合形状如何形成基本进化过程 人群。特定目标1将开发统计数据，以检测通过 利用局部祖先信息来结合混合对单倍型结构的影响。这些新 统计信息将集成到开放式软件中，并应用于在模拟和 代表各种人口统计的经验数据。特定的目标2将测试混合方式的结合 在源人群中发现的有害变化的不同分布。跟踪频率 隔离有害等位基因及其在同性恋运行中的成员资格将决定混合 重组的景观调节有害变化的暴露。表征 混合种群及其源人群中有害变化的动态将提供一个窗口 混合如何改变遗传负荷。该建议将推进研究自然的方法 在混合种群中进行选择，并阐明如何正面和负选择形状模式 遗传变异和疾病的风险在被研究的混合种群中。

项目成果

Rapid adaptation to malaria facilitated by admixture in the human population of Cabo Verde.

• DOI: 10.7554/elife.63177
• 发表时间: 2021-01-04
• 期刊: eLife
• 影响因子: 7.7
• 作者: Hamid I;Korunes KL;Beleza S;Goldberg A
• 通讯作者: Goldberg A

Human genetic admixture through the lens of population genomics.

• DOI: 10.1098/rstb.2020.0410
• 发表时间: 2022-06-06
• 期刊: PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
• 影响因子: 6.3
• 作者: Gopalan, Shyamalika;Smith, Samuel Pattillo;Korunes, Katharine;Hamid, Iman;Ramachandran, Sohini;Goldberg, Amy
• 通讯作者: Goldberg, Amy

Human genetic admixture.

• DOI: 10.1371/journal.pgen.1009374
• 发表时间: 2021-03
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Korunes KL;Goldberg A
• 通讯作者: Goldberg A

Localizing Post-Admixture Adaptive Variants with Object Detection on Ancestry-Painted Chromosomes.

• DOI: 10.1093/molbev/msad074
• 发表时间: 2023-04-04
• 期刊: MOLECULAR BIOLOGY AND EVOLUTION
• 影响因子: 10.7
• 作者: Hamid, Iman;Korunes, Katharine L.;Schrider, Daniel R.;Goldberg, Amy
• 通讯作者: Goldberg, Amy

Sex-biased admixture and assortative mating shape genetic variation and influence demographic inference in admixed Cabo Verdeans.

• DOI: 10.1093/g3journal/jkac183
• 发表时间: 2022-09-30
• 期刊: G3 (Bethesda, Md.)