Mitonuclear Interaction and the Genetic Architecture of Phenotypic Evolution

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This project will evaluate how mitochondrial dysfunction and mitochondrial-nuclear interaction contribute to evolution across three levels of biological organization - molecular-genetic, cellular, and organismal. The PIs will study evolutionary process within the context of the mitochondrial electron transport chain (ETC). Evolution experiments using ETC-deficient Caenorhabditis elegans nematodes will be combined with whole-genome sequencing, bioinformatics and mitochondrial phenotyping to study the genetic bases of maladaptive and compensatory adaptive evolution - the process whereby natural selection favors changes at loci that compensate for the deleterious effects of a mutant allele. The ETC is crucial for eukaryotic life and its proper functioning relies on the maintenance of favorable mitonuclear interactions; it is thus ideal for studying the patterns and functional bases of both forms of evolution and the role of mutation in shaping mitonuclear genome integration. Further, ETC dysfunction is a proposed cause of variation in genome-wide spontaneous mutation rates. This work will reveal the effects of different forms of ETC damage on nuclear and mitochondrial genome stability and concomitant changes in mitochondrial function and organismal fitness. Because few studies have addressed the population-level consequences of compensatory mutation or the genetic mechanisms of compensatory evolution in eukaryotic systems, and because mitochondrial metabolism and ETC function are highly evolutionarily conserved, findings are expected to be of broad interest and relevant to other eukaryotes.Broader Impacts. The project will train students in cutting-edge genomics research, provide important data and resources to the scientific community, and expand both PIs' educational and outreach activities. Minority and other students with gain meaningful research and science education experience. The PIs will co-train graduate and undergraduate students, participate in science outreach to minority student groups and a local Native American high school, and develop bioinformatics learning modules based on the research to be taught in their respective undergraduate Genetics courses at Portland State University and Oregon State University.