Historically, mtDNA was considered a selectively neutral marker that was useful for estimating the population genetic history of the maternal lineage. Over time there has been an increasing appreciation of mtDNA and mitochondria in maintaining cellular and organismal health. Beyond energy production, mtDNA and mitochondria have critical cellular roles in signalling. Here we briefly review the structure of mtDNA and the role of the mitochondrion in energy production. We then discuss the predictions that can be obtained from quaternary structure modelling and focus on mitochondrial complex I. Complex I is the primary entry point for electrons into the electron transport system is the largest respiratory complex of the chain and produces about 40% of the proton flux used to synthesize ATP. A focus of the review is Drosophila's utility as a model organism to study the selective advantage of specific mutations. However, we note that the incorporation of insights from a multitude of systems is necessary to fully understand the range of roles that mtDNA has in organismal fitness. We speculate that dietary changes can illicit stress responses that influence the selective advantage of specific mtDNA mutations and cause spatial and temporal fluctuations in the frequencies of mutations. We conclude that developing our understanding of the roles mtDNA has in determining organismal fitness will enable increased evolutionary insight and propose we can no longer assume it is evolving as a strictly neutral marker without testing this hypothesis.
Keywords: Reactive oxygen species; diet; macronutrients; mito-nuclear interactions.