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Dissertation Research: Genetic Architecture of Adaptive Evolution in Mitochondrial Physiology

论文研究：线粒体生理学适应性进化的遗传结构

基本信息

批准号：
1407000
负责人：
Walter Eanes
金额：
$ 1.87万
依托单位：
SUNY at Stony Brook
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-01 至 2017-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1407000&HistoricalAwards=false
关键词：
Dissertation Research Genetic Architecture Adaptive

项目摘要

Genetic architecture is the pattern and organization of genetic effects controlling phenotypic variation. I take an experimental approach to dissecting genetic architecture for the bioenergetic process of oxidative phosphorylation, a metabolic pathway central to energy use. Using the fruit fly, Drosophila melanogaster, I will systematically alter each of the enzymes involved in this pathway, and then measure the effect on the flow of electrons through the whole respiratory chain. Because these effects define the genetic architecture of this pathway and determine the response to natural selection, I hypothesize that the strength of the effect dictates the mode of selection acting on genes of the respiratory chain and membrane lipid metabolism. This metabolic control hypothesis makes explicit predictions for molecular patterns of polymorphism and divergence which I will test using genomic data from D. melanogaster and D. simulans. A major goal of modern biology is understanding the complexity of phenotypes and their underlying genetic architecture. Purely statistical approaches to genetic architecture of complex traits (e.g., cardiovascular disease) have had mixed success. The type of metabolic control analysis done in this study is routinely used to diagnose metabolic and mitochondrial pathologies. By quantifying the full control distribution for this complex trait we may better uderstand the causes of such diseases. In addition, this project will involve the mentoring of undergraduate students.

遗传结构是控制表型变异的遗传效应的模式和组织。我采取实验的方法来解剖氧化磷酸化的生物能量过程的遗传结构，这是一种对能量使用至关重要的代谢途径。我将利用果蝇（Drosophila melanogaster）系统地改变参与这一途径的每一种酶，然后测量对整个呼吸链中电子流动的影响。由于这些影响定义了这一途径的遗传结构，并确定了对自然选择的反应，我假设，该效应的强度决定了作用于呼吸链和膜脂代谢基因的选择模式。这种代谢控制假说对多态性和趋异的分子模式做出了明确的预测，我将用D。黑腹果蝇D. simulans。现代生物学的一个主要目标是了解表型的复杂性及其潜在的遗传结构。复杂性状的遗传结构的有效统计方法（例如，心血管疾病）取得了好坏参半的成功。本研究中进行的代谢控制分析类型通常用于诊断代谢和线粒体病理。通过量化这一复杂性状的完全控制分布，我们可以更好地理解这类疾病的原因。此外，该项目将涉及对本科生的指导。