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.

项目概要 全球各地的人口都是由混合所塑造的——先前不同群体之间的基因流动 组。通过混合将先前不同的基因型突然组合可以迅速改变等位基因 连锁不平衡的频率、杂合性和模式。这些过程创造了新材料 积极和消极选择的作用，但也取决于独立的适应历史 来源人群。混合群体还提供了强大的测试用例来了解选择如何进行 总体上塑造了进化，因为混合种群中祖先模式的变化更容易 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 由于混合物无处不在，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；因为混合后的选择通常在很短的时间内进行，并且混合后 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。缺乏 适当方法的缺乏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中的选择 不同的来源群体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——正向选择和负向选择——如何塑造人类的遗传学。 混合人群。该提案结合了方法开发和实证分析以提供见解 研究混合如何塑造多个混合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群体中的正选择： 利用当地血统信息来纳入混合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模拟中的选择。 代表不同人口统计情景的经验数据。具体目标 2 将测试混合物如何结合 在源群体中发现的有害变异的独特分布。追踪频率 分离有害等位基因及其在纯合性运行中的成员资格将决定混合方式 重组景观调节有害变异的暴露。表征 混合种群及其源种群有害变异的动态将提供一个窗口 研究混合物如何改变遗传负荷。该提案将推进自然研究的方法 混合群体中的选择，并阐明正选择和负选择如何塑造混合群体的模式 未充分研究的混合人群中的遗传变异和疾病风险。

项目成果

Human genetic admixture through the lens of population genomics.

通过群体基因组学的视角观察人类基因混合物。

• 发表时间: 2022-06-06
• 作者: Gopalan, Shyamalika;Smith, Samuel Pattillo;Korunes, Katharine;Hamid, Iman;Ramachandran, Sohini;Goldberg, Amy
• 通讯作者: Goldberg, Amy

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

佛得角人口的混合促进了对疟疾的快速适应。

• 发表时间: 2021-01-04
• 影响因子: 7.7
• 作者: Hamid, Iman;Korunes, Katharine L;Beleza, Sandra;Goldberg, Amy
• 通讯作者: Goldberg, Amy

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

通过祖先染色染色体上的目标检测来定位混合后自适应变体。

• 发表时间: 2023-04-04
• 影响因子: 10.7
• 作者: Hamid, Iman;Korunes, Katharine L;Schrider, Daniel R;Goldberg, Amy
• 通讯作者: Goldberg, Amy

Human genetic admixture.

人类基因混合物。

• 发表时间: 2021-03
• 影响因子: 4.5
• 作者: Korunes, Katharine L;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.

性别偏见的混合和选型交配塑造了遗传变异，并影响了混合佛得角人的人口统计推断。

• 发表时间: 2022-09-30
• 作者: Korunes, Katharine L;Soares;Bobrek, Katherine;Tang, Hua;Araújo, Isabel Inês;Goldberg, Amy;Beleza, Sandra
• 通讯作者: Beleza, Sandra