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.
