Affiliations: 1) New York University; 2) Binghamton University
Keywords: Genetic interactions
The maintenance and heredity of functional mitochondrial DNA (mtDNA) is critical for mitochondrial function and organismal fitness. Because coordination between the mtDNA and nuclear genome is required, selection for mitonuclear interactions that stabilize mtDNAs should be important in shaping mitonuclear coevolution. Understanding and mapping evolutionary important mitonuclear interactions is a major goal in biology. Here, we use the small colony, petite, phenotype of Saccharomyces yeasts that is produced in the absence of a functional mitochondrial respiratory chain to explore the role of natural genetic variation in mtDNA maintenance and stability. We found that mtDNA stability is a complex trait influenced by mtDNA-dependent mitonuclear interactions, and that, in at least one population, selection has coadapted mitonuclear interactions that increase mtDNA stability. To map mitonuclear interactions, we created a multiparent introgressed recombinant panel of S. cerevisiae yeasts originating from 25 natural isolates and three mtDNAs and built an association model to identify SNPs that were dependent or independent of mitotype. Mitonuclear interacting SNPs associating with mtDNA stability included genes involved in mitotic cell growth. We found that in natural isolates, and laboratory-induced conditions, mtDNA stabilities correlated with growth rates, suggesting a fitness tradeoff between rapid cell division and mitochondrial health. SNPs that associated with rates of mtDNA loss in ways that were independent of mitotype included alleles of MIP1, the mitochondrial DNA polymerase as well as other genes with known association with mitochondrial activities. This work presents a new tool for mapping mitonuclear interactions and promotes the idea that evolutionary important mitonuclear interactions can influence intracellular signaling pathways.