Genome evolution across complex trait hierarchies

跨复杂性状层次的基因组进化

基本信息

批准号：
10623062
负责人：
Elizabeth Griep King
金额：
$ 40.4万
依托单位：
UNIVERSITY OF MISSOURI-COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-01 至 2028-03-31
项目状态：
未结题

项目摘要

Project Summary Most human health traits are highly complex and hierarchical, in which a high-level trait (e.g., energy expenditure) is the product of the combined effects of a suite of sub-phenotypes. These trait hierarchies are typically influenced by many genetic variants of small effect that interact with one another and with environmental factors, making the identification of the causative variants a significant challenge. As a result, past research strategies have largely failed to fully address the complexity of most complex traits, leaving a significant knowledge gap in our understanding of the genetic basis of these traits. This project will use an innovative combination of a large multiparent mapping population and experimental evolution using the powerful fruit fly model system to identify the common mechanistic connections between complex traits and observe how these connections influence multitrait evolution. First, this project will simultaneously evolve flies targeting multiple trait hierarchies and track the genomic and phenotypic changes that occur during adaptation. Second, this project will leverage a large multiparent mapping population that has been used broadly in the genetics community to address fundamental questions about the generality of emergent properties of the genome, such as the extent of pleiotropy, genotype by environment interactions, and genetic background effects. Overall, this research will provide generalizable lessons about how genomes are connected to physiology to produce the interconnected set of traits that affect health across the lifespan.

项目概要大多数人类健康特征是高度复杂和分层的，其中高级特征（例如能量消耗）是一系列亚表型综合作用的产物。这些特质层次结构通常是受到许多相互影响以及与环境因素相互作用的微小影响的遗传变异的影响，使得识别致病变异成为一项重大挑战。因此，过去的研究策略在很大程度上未能完全解决最复杂特征的复杂性，从而在我们对这些性状遗传基础的理解。该项目将采用大型创新组合使用强大的果蝇模型系统进行多亲本作图种群和实验进化识别复杂特征之间的常见机制联系，并观察这些联系如何影响多性状进化。首先，该项目将同时进化针对多个性状层次结构的果蝇并跟踪适应过程中发生的基因组和表型变化。其次，该项目将利用大量多亲本群体作图已在遗传学界广泛用于解决基本问题关于基因组新兴特性的普遍性的问题，例如多效性的程度、基因型受环境相互作用和遗传背景影响。总的来说，这项研究将提供可推广的关于基因组如何与生理学联系起来以产生影响的相互关联的特征集的课程整个生命周期的健康。