Mitochondrial Genome Variation Affects Multiple Respiration and Nonrespiration Phenotypes in Saccharomyces cerevisiae

Mitochondrial genome variation and its effects on phenotypes have been widely analyzed in higher eukaryotes but less so in the model eukaryote Saccharomyces cerevisiae. Here, we describe mitochondrial genome variation in 96 diverse S. cerevisiae strains and assess associations between mitochondrial...

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Vydáno v:	Genetics (Austin) Ročník 211; číslo 2; s. 773 - 786
Hlavní autoři:	Vijayraghavan, Sriram, Kozmin, Stanislav G, Strope, Pooja K, Skelly, Daniel A, Lin, Zhenguo, Kennell, John, Magwene, Paul M, Dietrich, Fred S, McCusker, John H
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Genetics Society of America 01.02.2019
Témata:	Antifungal Agents - toxicity ATP synthase ATP6 protein Cell Respiration - genetics Copper - toxicity Cycloheximide Cycloheximide - toxicity Deoxyribonucleic acid Disease DNA Drug Resistance, Fungal - genetics Electron transport Epistasis Epistasis, Genetic Eukaryotes Gene expression Genetics Genome, Mitochondrial Genomes Genomics Genotype & phenotype Genotypes Hemizygosity Investigations Ketoconazole Ketoconazole - toxicity Mitochondria Mitochondrial DNA Mitochondrial Proton-Translocating ATPases - genetics Mutation Oligomycin Phenotype Phenotypes Polymorphism, Genetic Polymorphism, Single Nucleotide Proteins Quantitative genetics Respiration Saccharomyces cerevisiae Saccharomyces cerevisiae - drug effects Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae Proteins - genetics Single-nucleotide polymorphism Strains (organisms) Transfer RNA Variation Yeast mitochondrial genome variation transgression Introgression Saccharomyces cerevisiae phenotypic variation nuclear-mitochondrial epistasis
ISSN:	1943-2631, 0016-6731, 1943-2631
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Shrnutí:	Mitochondrial genome variation and its effects on phenotypes have been widely analyzed in higher eukaryotes but less so in the model eukaryote Saccharomyces cerevisiae. Here, we describe mitochondrial genome variation in 96 diverse S. cerevisiae strains and assess associations between mitochondrial genotype and phenotypes as well as nuclear-mitochondrial epistasis. We associate sensitivity to the ATP synthase inhibitor oligomycin with SNPs in the mitochondrially encoded ATP6 gene. We describe the use of iso-nuclear F1 pairs, the mitochondrial genome equivalent of reciprocal hemizygosity analysis, to identify and analyze mitochondrial genotype-dependent phenotypes. Using iso-nuclear F1 pairs, we analyze the oligomycin phenotype-ATP6 association and find extensive nuclear-mitochondrial epistasis. Similarly, in iso-nuclear F1 pairs, we identify many additional mitochondrial genotype-dependent respiration phenotypes, for which there was no association in the 96 strains, and again find extensive nuclear-mitochondrial epistasis that likely contributes to the lack of association in the 96 strains. Finally, in iso-nuclear F1 pairs, we identify novel mitochondrial genotype-dependent nonrespiration phenotypes: resistance to cycloheximide, ketoconazole, and copper. We discuss potential mechanisms and the implications of mitochondrial genotype and of nuclear-mitochondrial epistasis effects on respiratory and nonrespiratory quantitative traits.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Present address: The Jackson Laboratory, Bar Harbor, ME 04609. Present address: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20892. Present address: Department Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3411.
ISSN:	1943-2631 0016-6731 1943-2631
DOI:	10.1534/genetics.118.301546