Dissertation Research: Genetic Architecture of Adaptive Evolution in Mitochondrial Physiology

遗传结构是控制表型变异的遗传效应的模式和组织。我采用实验方法来剖析氧化磷酸化生物能量过程的遗传结构，氧化磷酸化是能量利用的核心代谢途径。我将利用果蝇（果蝇）系统地改变该途径中涉及的每种酶，然后测量对整个呼吸链电子流的影响。因为这些效应定义了该途径的遗传结构并决定了对自然选择的反应，所以我假设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分歧的分子模式做出了明确的预测，我将使用黑腹果蝇和拟果蝇的基因组数据来测试这些模式。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。 针对复杂性状（例如心血管疾病）的遗传结构的纯统计方法取得了不同程度的成功。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。通过量化这种复杂性状的完全控制分布，我们可以更好地了解此类疾病的原因。此外，该项目还将涉及本科生的指导。

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.