Genome evolution across complex trait hierarchies

项目摘要 大多数人类健康特征是高度复杂和层次分明的，其中一个高水平的特征(如能量消耗) 是一系列亚型综合作用的产物。这些特征层次结构通常是 受许多相互作用和与环境因素相互作用的小效应遗传变异的影响， 这使得对致病变种的识别成为一个重大的挑战。因此，过去的研究策略 在很大程度上未能完全解决大多数复杂性状的复杂性，留下了显著的知识缺口 我们对这些特征的遗传基础的理解。该项目将使用一种创新的组合， 利用功能强大的果蝇模型系统进行多亲本群体定位和实验进化 复杂性状之间的共同机制联系，并观察这些联系如何影响 多性状进化。首先，这个项目将同时进化以多个特征等级为目标的苍蝇并跟踪 适应过程中发生的基因组和表型变化。其次，这个项目将利用一个 在基因学界广泛使用的多亲作图群体，以解决基本问题 关于基因组突现特性的共性的问题，如多效性的程度、基因 受环境相互作用和遗传背景效应影响。总体而言，这项研究将提供可推广的 关于基因组如何与生理学相联系以产生相互关联的一组影响 生命中的健康。

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.