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Inferring the evolutionary history of admixed populations

推断混合种群的进化历史

基本信息

批准号：
10640128
负责人：
Amy Goldberg
金额：
$ 37.22万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
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

项目摘要

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--以前孤立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。混合种群的镶嵌祖先随着它们的基因组和个体之间的不同而不同，导致表型变异和疾病风险的差异。事实上，混合是最快的之一。进化过程极大地改变了种群的组成。然而，研究这些问题的方法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来源的线性组合，交配模式的缺失变化和迁移率随时间的变化。完毕在接下来的五年里，戈德堡实验室将把定量方法的开发与经验数据结合起来分析混合种群进化史的两个基本组成部分：1) 对中性和有害的变异模式的人口历史及其后果的推断，以及2) 混合前后正选择下的基因座特征。特别是，我们将延长我们的性别特定混合的机制模型，允许经验上观察到的非随机交配模式混杂种群。我们将应用这个模型来推断佛得角的人口历史，葡萄牙人和西非人的血统，测试不同岛屿之间交配模式的差异它们的大小和殖民史。在这一模式下，我们还将以佛得角为例研究人口学与混合种群有害变异的关系。接下来，我们将开发新的在混合前后使用混合基因组推断正选择的统计数据。外加剂可以两者都掩盖了积极选择的经典特征，并提供了新的遗传物质，在此基础上进行选择行动起来。因此，解释特定人口统计和选择性签名的方法混合了人口是必要的。我们将把这些统计数据整合到基于模拟的学习方法中，以使其易于访问。最后，我们将应用我们的新统计数据来超越假想的识别在多个混杂的非洲侨民中表征选择强度和选择时机的选择基因座不同环境中的种群。这一建议增强了我们对生物进化过程的理解混合种群，产生有用的统计方法，并阐明种群和选择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得天独厚的优势我们将精确的数学模型与现实的推理框架结合起来研究在混合群体中产生遗传变异的过程。