Inferring the evolutionary history of admixed populations

推断混合种群的进化历史

• 批准号: 10446815
• 负责人: Amy Goldberg
• 金额: $ 6.3万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10446815
• 关键词: Address; Admixture; African; Cape Verde; Case Study; Complex; Computational Technique; Data Analyses; Demography; Environment; Genes; Genetic Materials; Genetic Variation; Genome; Genomics; Goals; Health; Human; Individual; Island; Masks; Methods; Modeling; Mosaicism; Partner in relationship; Pattern; Phenotype; Population; Portuguese; Positioning Attribute; Process; Psychological Techniques; Recording of previous events; Source; Statistical Methods; Testing; Time; Variant; base; disorder risk; experience; learning strategy; mathematical model; method development; migration; offspring; risk prediction; sex; simulation game; statistics

Admixture—gene flow between previously isolated populations—has shaped the genomes of almost all human populations. The mosaic ancestry of admixed populations varies along their genomes and between individuals, leading to differences in phenotypic variation and disease risk. Indeed, admixture is one of the fastest evolutionary processes to dramatically change the composition of a population. Yet, methods to study the evolutionary history of admixed populations are lacking. Admixed populations are often considered as simple linear combinations of their sources, missing variation in mating patterns and migration rates over time. Over the next five years, the Goldberg lab will combine quantitative methods development with empirical data analysis to addresses two fundamental components of the evolutionary history of admixed populations: 1) inference of demographic history and its consequences for neutral and deleterious patterns of variation, and 2) characterization of loci under positive selection before and after admixture. Specially, we will extend our mechanistic model of sex-specific admixed to allow for non-random mating patterns empirically observed in admixed populations. We will apply this model to infer the demographic history of Cape Verdeans, with Portuguese and West African ancestry, testing for differences in mating patterns between islands that differ in their size and colonization history. Under this model, we will also use Cape Verde as a case study of the relationship between demography and deleterious variation in admixed populations. Next, we will develop new statistics to infer positive selection using admixed genomes both before and after admixture. Admixture can both mask classic signatures of positive selection, and provide new genetic material upon which selection can act. Therefore, methods that account for the specific demographic and selective signatures of admixed populations are necessary. We will incorporate these statistics into a simulation-based learning method to make it easily accessible. Finally, we will apply our new statistics to move beyond identification of putatively selected loci to characterize the strength and timing of selection in multiple admixed African diaspora populations in different environments. This proposal enhances our understanding of evolutionary processes in admixed populations, produces usable statistical methods, and elucidates the population and selective history of diverse global populations. The Goldberg lab is uniquely positioned to accomplish these goals because of our experience combining exact mathematical models with realistic inference frameworks to study the processes generating genetic variation in admixed groups.

混合--以前隔离的种群之间的基因流动--已经塑造了几乎所有人类的基因组 人口。混合种群的嵌合祖先沿着它们的基因组和个体之间变化， 导致表型变异和疾病风险的差异。的确，混合物是最快的 进化过程，以显着改变人口的组成。然而，研究 缺乏混合种群的进化史。混合种群通常被认为是简单的 它们的来源的线性组合，交配模式和迁移率随时间的变化。超过 在未来的五年里，戈德堡实验室将把联合收割机定量方法的发展与经验数据结合起来 分析解决了混合种群进化历史的两个基本组成部分：1） 人口统计学历史的推断及其对中性和有害变异模式的影响，以及2） 在混合之前和之后的正选择下的基因座的表征。特别是，我们将扩大我们的 性别特异性混合的机制模型，以允许经验观察到的非随机交配模式， 混合种群我们将应用这个模型来推断佛得角人的人口统计历史， 葡萄牙和西非血统，测试不同岛屿之间交配模式的差异， 他们的规模和殖民历史在这个模型下，我们还将使用佛得角作为案例研究， 混合种群中人口统计学与有害变异之间的关系。接下来，我们将开发新的 使用混合前后的混合基因组进行统计以推断阳性选择。掺合料能 两者都掩盖了正选择的经典特征，并提供了新的遗传物质， 法因此，考虑到特定的人口统计学和选择性特征的方法， 人口是必要的。我们将把这些统计数据纳入基于模拟的学习方法， 使其易于获取。最后，我们将应用新的统计数据， 选择位点来表征多个混合非洲侨民中选择的强度和时间 不同环境下的人群。这一建议增强了我们对进化过程的理解， 混合人口，产生可用的统计方法，并阐明人口和选择的历史 不同的全球人口。戈德堡实验室在实现这些目标方面具有独特的优势，因为 我们的经验结合精确的数学模型与现实的推理框架，研究 在混合群体中产生遗传变异的过程。