The Functional Basis of Genetic Interactions Underlying Quantitative Trait Variation

智力优势大多数遗传特征是定量的，由分布在基因组中的多个基因的变异决定。这些不同基因的遗传变异会以难以预测的方式相互作用。该项目旨在确定控制数量性状变异的基因之间关系的原则。本项目将在自然发生的数量性状变异的模型实验系统中研究遗传相互作用，并确定相互作用基因之间功能关系的一般原则。这项研究需要在精心定义的环境中进行进化实验，选择能够提高细胞生长速度的酵母突变体。实验将被设计成使突变体相对于初始菌株积累少量突变。该项目将使用全基因组重测序技术识别所有获得的遗传变异，并构建携带单个突变和所有可能的突变组合的菌株面板。它将量化每种基因型组合的生长速度，并确定基因变体之间相互作用的性质。然后，它将使用酵母基因组的广泛功能注释来研究以不同方式相互作用的基因之间的功能关系。正如基因及其产物在整个生命王国中都是保守的一样，基因之间的相互作用以及控制这些相互作用结果的原则也可能是保守的。因此，研究结果将有助于我们理解模式生物和非模式生物数量性状的遗传结构。更广泛的影响该项目将有助于了解基因如何与改善农业育种实践的潜在应用相互作用。这项工作将对本科和科学教育、纳入代表性不足的群体以及增强科学理解产生一系列更广泛的影响。该项目将包括本科生、未被充分代表的少数民族和主要本科院校的学生。它将包括在研究生和本科生阶段培训遗传学、计算生物学和微生物学方面的科学家。此外，该项目还将包括一个拓展计划，为高中生提供在实验室环境中工作的机会。来自不同背景的高中学生将接受实验和计算生物学的培训，并在实验室进行独立的研究项目。该项目将提供指导，以便高中生能够将他们的研究提交给国家科学竞赛。与该计划相结合的是，将为本科生开设一门新的综合课程，将统计学、遗传学和计算机教学结合起来。

Intellectual MeritMost inherited traits are quantitative and determined by variation in multiple genes dispersed throughout the genome. Genetic variation in these different genes can interact in ways that are difficult to predict. The project aims to identify principles governing relationships between genes that underlie quantitative trait variation. This project will study genetic interactions in a model experimental system for naturally occurring quantitative trait variation and identify general principles regarding the functional relationships between interacting genes. The research entails selecting yeast mutants that have increased cell growth rates by performing evolution experiments in carefully defined environments. Experiments will be designed so that mutants accumulate a small number of mutations relative to the founding strain. This project will identify all the acquired genetic variation using whole genome resequencing and construct a panel of strains carrying individual mutations and all possible combinations of mutations. It will quantify growth rates for each genotype combination and determine the nature of the interactions between the gene variants. It will then study the functional relationships between genes that interact in different ways using the extensive functional annotation available for the yeast genome. Just as genes and their products are conserved across the kingdoms of life, interactions between genes, and the principles that govern the outcome of those interactions, are likely to be conserved. Thus, findings from the study will inform our understanding of the genetic architecture of quantitative traits in model and non-model organisms.Broader ImpactsThe project will contribute to an understanding of how genes interact with potential applications to improving agricultural breeding practices. This work will have a number of broader impacts in undergraduate and science education, inclusion of underrepresented groups, and enhancement of scientific understanding. The project will include undergraduates, underrepresented minorities and students from primarily undergraduate institutions. It will involve training scientists in genetics, computational biology and microbiology at the graduate and undergraduate level. In addition, the project will include an outreach program that provides high school students with the opportunity to work in a laboratory environment. High school students from diverse backgrounds will be provided with training in experimental and computational biology and undertake an independent research project in the laboratory. The project will provide mentorship so that high school students can submit their research to national science competitions. Concomitant with the proposed project, a new integrative course for undergraduate students will be developed that combines instruction in statistics, genetics and computing.