title: A mitochondrial DNA hypomorph of cytochrome oxidase specifically impairs male fertility in Drosophila melanogaster.
abstract: Due to their strict maternal inheritance in most animals and plants, mitochondrial genomes are predicted to accumulate mutations that are beneficial or neutral in females but harmful in males. Although a few male-harming mtDNA mutations have been identified, consistent with this 'Mother's Curse', their effect on females has been largely unexplored. Here, we identify COII(G177S), a mtDNA hypomorph of cytochrome oxidase II, which specifically impairs male fertility due to defects in sperm development and function without impairing other male or female functions. COII(G177S) represents one of the clearest examples of a 'male-harming' mtDNA mutation in animals and suggest that the hypomorphic mtDNA mutations like COII(G177S) might specifically impair male gametogenesis. Intriguingly, some D. melanogaster nuclear genetic backgrounds can fully rescue COII(G177S) -associated sterility, consistent with previously proposed models that nuclear genomes can regulate the phenotypic manifestation of mtDNA mutations.
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.|Howard Hughes Medical Institute, Seattle, United States.|Department of Biological Sciences, Vanderbilt University, Nashville, United States.
authors.forename: Maulik R
authors.initials: MR
authors.lastname: Patel
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
authors.forename: Ganesh K
authors.initials: GK
authors.lastname: Miriyala
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
authors.forename: Aimee J
authors.initials: AJ
authors.lastname: Littleton
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, United States.|Howard Hughes Medical Institute, University of Michigan, Ann Arbor, United States.
authors.forename: Heiko
authors.initials: H
authors.lastname: Yang
authors.affiliation: Genome Sciences, University of Washington, Seattle, United States.
authors.forename: Kien
authors.initials: K
authors.lastname: Trinh
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
authors.forename: Janet M
authors.identifier: 0000-0001-8220-8427
authors.initials: JM
authors.lastname: Young
authors.affiliation: Pathology, University of Washington Medical Center, Seattle, United States.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Kennedy
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, United States.|Howard Hughes Medical Institute, University of Michigan, Ann Arbor, United States.
authors.forename: Yukiko M
authors.initials: YM
authors.lastname: Yamashita
authors.affiliation: Genome Sciences, University of Washington, Seattle, United States.
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Pallanck
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.|Howard Hughes Medical Institute, Seattle, United States.
authors.forename: Harmit S
authors.identifier: 0000-0001-6005-0016
authors.initials: HS
authors.lastname: Malik
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D003576:Electron Transport Complex IV / Q000235:genetics*; D007246:Infertility / Q000235:genetics*; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics*; D020125:Mutation, Missense
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV
keywords: D. melanogaster; cell biology; evolutionary biology; experimental evolution; genetic suppressors; genomics; lifespan; male fertility; mitochondrial DNA; sperm development