DISSERTATION RESEARCH: Mitochondrial Epistasis in Yeast

Suny At Binghamton, Binghamton NY

Investigators

Abstract

This project will investigate how interactions among mitochondrial genes influence mitochondrial function and evolution. Mitochondria produce much of the energy used by cells, and this production depends upon precise interactions of multiple genes. Currently, interactions among mitochondrial genes have not been demonstrated, mainly because these genes are normally inherited as a single unit from the mother and such uniparental inheritance makes it difficult to study gene interactions. To get around this challenge, the researchers will study baker's yeast (Saccharomyces cerevisiae), which inherit mitochondrial DNA from both parents. They will first generate unique combinations of mitochondrial genes from a large yeast population to evaluate how these influence energy production. Then they will sequence single mitochondrial genomes to identify the specific genes involved. The project will advance our understanding of the mechanics of mitochondrial protein interactions and how they shape evolution. Additionally, the research will be integrated into a genetics laboratory course and engage 128 undergraduate students in hands-on research. Respiratory function relies on compatible interactions between nuclear and mitochondrial genes, which leads to mitochondrial-nuclear epistasis and, theoretically, interactions between mitochondrial genes (mt-mt epistasis). Natural variation in mtDNAs contributes to differences in fitness, but because mtDNAs are typically uniparentally inherited and do not recombine, it is difficult to functionally dissect individual vs. epistatic effects of mtDNA polymorphisms. The yeast Saccharomyces cerevisiae has bi-parental inheritance and recombination of mtDNAs. The natural distribution of mt-mt epistasis will be assessed by mating strains with identical nuclear genotypes but divergent mtDNAs, and the resulting strains containing mitochondrial recombinants will be functionally screened for evidence of mt-mt epistasis. Individual mitochondrial recombinant genomes will be sequenced and interacting loci mapped by comparing differences in allele pair frequencies between phenotypically distinct groups. This research will determine the role mt-mt epistasis plays in natural populations and provide information on mitochondrial recombination in yeast at the resolution of individual recombinant mtDNA haplotypes.