Genetics and Athletics: Genetic Variation in Mitochondrial DNA Copy Number and the Response to Endurance Exercise Training in Drosophila melanogaster

Abstract

Many physical performance-related traits have been shown to exhibit genetic variation. Mitochondrial DNA copy number plays an important role in determining aerobic capacity and therefore overall health and physical performance. However, few studies have identified genetic determinants of interindividual variation in this trait at a baseline level or post-exercise. Some factors controlling the process of mtDNA regulation additionally remain unknown. This project therefore first explores the genetic variability and heritability of baseline mtDNA copy number. By screening the Drosophila Genetic Reference Panel (DGRP) for variation in mtDNA content and then performing a GWAS using mtDNA copy number as the trait, I identify 22 highly significant SNPs (p < 10^9) associated with mtDNA content within 7 regions of the nuclear genome. None of the genes within these loci have been associated with mtDNA copy number regulation before. Upon finding that mtDNA content is genetically variable, heritable, and highly associated with these genomic regions, I then investigate how plastic mtDNA copy number is in Drosophila in response to endurance exercise training. I also study changes in a number of other phenotypes known to be affected by prolonged exercise, including body size, activity levels, and sleep. Since these traits may be affected differently in Drosophila as compared to humans and other vertebrate species, these observations are important in determining the validity of Drosophila melanogaster as a model organism for further studies that examine genetic variation in the responses to exercise training. I find that endurance exercise training significantly increases mtDNA copy number, decreases body size and activity levels, and has no significant effect on sleep patterns in Drosophila.