Early Dynamics of Newly Arising Mitochondrial Variants: Relative Roles of Intra- versus Inter-individual Selection in Taming Renegade Elements

Mitochondrial genomes, which exist in multiple copies within cells and replicate independently from the nuclear genome, can compete for replication and transmission within individuals.

Harmful mitochondrial DNA (mtDNA) mutations with a transmission advantage have been described as “selfish” and are thought to contribute to multiple biological phenomena including aging, neurogenerative diseases, and speciation.

Evidence suggests that “selfish” mtDNA exploit mitochondrial quality-control processes in cells for their proliferation. Using C. elegans, I will test the fitness effects of new mtDNA mutations and how they influence gene expression.

Furthermore, I will knockdown expression of key genes controlling mitochondrial maintenance under conditions that distinguish between selection on mtDNA within and between individuals.

These experiments will be performed on a diverse set of new mtDNA variants including synonymous and nonsynonymous substitutions, frameshifts, gene deletions and an internal duplication.

Together, these aims will significantly enhance our understanding of the early evolution of new mtDNA variants regards (i) fitness effects, (ii) their transcriptional and functional consequences, and (iii) the mechanistic basis of mitonuclear genomic conflict.

Because mitochondrial metabolism and ETC function are highly evolutionarily conserved, the fundamental nature of these questions is expected to be relevant to other eukaryotes and of broad interest to other researchers.