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Lethal Interaction of Nuclear and Mitochondrial Genotypes in Drosophila melanogaster
Drosophila melanogaster, like most animal species, displays considerable genetic variation in both nuclear and mitochondrial DNA (mtDNA). Here we tested whether any of four natural mtDNA variants was able to modify the effect of the phenotypically mild, nuclear tko(25t) mutation, affecting mitochond...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Genetics Society of America
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643882/ https://www.ncbi.nlm.nih.gov/pubmed/31076384 http://dx.doi.org/10.1534/g3.119.400315 |
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author | Salminen, Tiina S. Cannino, Giuseppe Oliveira, Marcos T. Lillsunde, Päivi Jacobs, Howard T. Kaguni, Laurie S. |
author_facet | Salminen, Tiina S. Cannino, Giuseppe Oliveira, Marcos T. Lillsunde, Päivi Jacobs, Howard T. Kaguni, Laurie S. |
author_sort | Salminen, Tiina S. |
collection | PubMed |
description | Drosophila melanogaster, like most animal species, displays considerable genetic variation in both nuclear and mitochondrial DNA (mtDNA). Here we tested whether any of four natural mtDNA variants was able to modify the effect of the phenotypically mild, nuclear tko(25t) mutation, affecting mitochondrial protein synthesis. When combined with tko(25t), the mtDNA from wild strain KSA2 produced pupal lethality, accompanied by the presence of melanotic nodules in L3 larvae. KSA2 mtDNA, which carries a substitution at a conserved residue of cytochrome b that is predicted to be involved in subunit interactions within respiratory complex III, conferred drastically decreased respiratory capacity and complex III activity in the tko(25t) but not a wild-type nuclear background. The complex III inhibitor antimycin A was able to phenocopy effects of the tko(25t) mutation in the KSA2 mtDNA background. This is the first report of a lethal, nuclear-mitochondrial interaction within a metazoan species, representing a paradigm for understanding genetic interactions between nuclear and mitochondrial genotype relevant to human health and disease. |
format | Online Article Text |
id | pubmed-6643882 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Genetics Society of America |
record_format | MEDLINE/PubMed |
spelling | pubmed-66438822019-07-25 Lethal Interaction of Nuclear and Mitochondrial Genotypes in Drosophila melanogaster Salminen, Tiina S. Cannino, Giuseppe Oliveira, Marcos T. Lillsunde, Päivi Jacobs, Howard T. Kaguni, Laurie S. G3 (Bethesda) Investigations Drosophila melanogaster, like most animal species, displays considerable genetic variation in both nuclear and mitochondrial DNA (mtDNA). Here we tested whether any of four natural mtDNA variants was able to modify the effect of the phenotypically mild, nuclear tko(25t) mutation, affecting mitochondrial protein synthesis. When combined with tko(25t), the mtDNA from wild strain KSA2 produced pupal lethality, accompanied by the presence of melanotic nodules in L3 larvae. KSA2 mtDNA, which carries a substitution at a conserved residue of cytochrome b that is predicted to be involved in subunit interactions within respiratory complex III, conferred drastically decreased respiratory capacity and complex III activity in the tko(25t) but not a wild-type nuclear background. The complex III inhibitor antimycin A was able to phenocopy effects of the tko(25t) mutation in the KSA2 mtDNA background. This is the first report of a lethal, nuclear-mitochondrial interaction within a metazoan species, representing a paradigm for understanding genetic interactions between nuclear and mitochondrial genotype relevant to human health and disease. Genetics Society of America 2019-05-10 /pmc/articles/PMC6643882/ /pubmed/31076384 http://dx.doi.org/10.1534/g3.119.400315 Text en Copyright © 2019 Salminen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Investigations Salminen, Tiina S. Cannino, Giuseppe Oliveira, Marcos T. Lillsunde, Päivi Jacobs, Howard T. Kaguni, Laurie S. Lethal Interaction of Nuclear and Mitochondrial Genotypes in Drosophila melanogaster |
title | Lethal Interaction of Nuclear and Mitochondrial Genotypes in Drosophila melanogaster |
title_full | Lethal Interaction of Nuclear and Mitochondrial Genotypes in Drosophila melanogaster |
title_fullStr | Lethal Interaction of Nuclear and Mitochondrial Genotypes in Drosophila melanogaster |
title_full_unstemmed | Lethal Interaction of Nuclear and Mitochondrial Genotypes in Drosophila melanogaster |
title_short | Lethal Interaction of Nuclear and Mitochondrial Genotypes in Drosophila melanogaster |
title_sort | lethal interaction of nuclear and mitochondrial genotypes in drosophila melanogaster |
topic | Investigations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643882/ https://www.ncbi.nlm.nih.gov/pubmed/31076384 http://dx.doi.org/10.1534/g3.119.400315 |
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