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Mitochondrial-Nuclear Interactions Mediate Sex-Specific Transcriptional Profiles in Drosophila

The assembly and function of mitochondria require coordinated expression from two distinct genomes, the mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Mutations in either genome can be a source of phenotypic variation, yet their coexpression has been largely overlooked as a source of variation, p...

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Autores principales: Mossman, Jim A., Tross, Jennifer G., Li, Nan, Wu, Zhijin, Rand, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Genetics Society of America 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068850/
https://www.ncbi.nlm.nih.gov/pubmed/27558138
http://dx.doi.org/10.1534/genetics.116.192328
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author Mossman, Jim A.
Tross, Jennifer G.
Li, Nan
Wu, Zhijin
Rand, David M.
author_facet Mossman, Jim A.
Tross, Jennifer G.
Li, Nan
Wu, Zhijin
Rand, David M.
author_sort Mossman, Jim A.
collection PubMed
description The assembly and function of mitochondria require coordinated expression from two distinct genomes, the mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Mutations in either genome can be a source of phenotypic variation, yet their coexpression has been largely overlooked as a source of variation, particularly in the emerging paradigm of mitochondrial replacement therapy. Here we tested how the transcriptome responds to mtDNA and nDNA variation, along with mitonuclear interactions (mtDNA × nDNA) in Drosophila melanogaster. We used two mtDNA haplotypes that differ in a substantial number of single nucleotide polymorphisms, with >100 amino acid differences. We placed each haplotype on each of two D. melanogaster nuclear backgrounds and tested for transcription differences in both sexes. We found that large numbers of transcripts were differentially expressed between nuclear backgrounds, and that mtDNA type altered the expression of nDNA genes, suggesting a retrograde, trans effect of mitochondrial genotype. Females were generally more sensitive to genetic perturbation than males, and males demonstrated an asymmetrical effect of mtDNA in each nuclear background; mtDNA effects were nuclear-background specific. mtDNA-sensitive genes were not enriched in male- or female-limited expression space in either sex. Using a variety of differential expression analyses, we show the responses to mitonuclear covariation to be substantially different between the sexes, yet the mtDNA genes were consistently differentially expressed across nuclear backgrounds and sexes. Our results provide evidence that the main mtDNA effects can be consistent across nuclear backgrounds, but the interactions between mtDNA and nDNA can lead to sex-specific global transcript responses.
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spelling pubmed-50688502016-10-21 Mitochondrial-Nuclear Interactions Mediate Sex-Specific Transcriptional Profiles in Drosophila Mossman, Jim A. Tross, Jennifer G. Li, Nan Wu, Zhijin Rand, David M. Genetics Investigations The assembly and function of mitochondria require coordinated expression from two distinct genomes, the mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Mutations in either genome can be a source of phenotypic variation, yet their coexpression has been largely overlooked as a source of variation, particularly in the emerging paradigm of mitochondrial replacement therapy. Here we tested how the transcriptome responds to mtDNA and nDNA variation, along with mitonuclear interactions (mtDNA × nDNA) in Drosophila melanogaster. We used two mtDNA haplotypes that differ in a substantial number of single nucleotide polymorphisms, with >100 amino acid differences. We placed each haplotype on each of two D. melanogaster nuclear backgrounds and tested for transcription differences in both sexes. We found that large numbers of transcripts were differentially expressed between nuclear backgrounds, and that mtDNA type altered the expression of nDNA genes, suggesting a retrograde, trans effect of mitochondrial genotype. Females were generally more sensitive to genetic perturbation than males, and males demonstrated an asymmetrical effect of mtDNA in each nuclear background; mtDNA effects were nuclear-background specific. mtDNA-sensitive genes were not enriched in male- or female-limited expression space in either sex. Using a variety of differential expression analyses, we show the responses to mitonuclear covariation to be substantially different between the sexes, yet the mtDNA genes were consistently differentially expressed across nuclear backgrounds and sexes. Our results provide evidence that the main mtDNA effects can be consistent across nuclear backgrounds, but the interactions between mtDNA and nDNA can lead to sex-specific global transcript responses. Genetics Society of America 2016-10 2016-08-24 /pmc/articles/PMC5068850/ /pubmed/27558138 http://dx.doi.org/10.1534/genetics.116.192328 Text en Copyright © 2016 by the Genetics Society of America Available freely online through the author-supported open access option.
spellingShingle Investigations
Mossman, Jim A.
Tross, Jennifer G.
Li, Nan
Wu, Zhijin
Rand, David M.
Mitochondrial-Nuclear Interactions Mediate Sex-Specific Transcriptional Profiles in Drosophila
title Mitochondrial-Nuclear Interactions Mediate Sex-Specific Transcriptional Profiles in Drosophila
title_full Mitochondrial-Nuclear Interactions Mediate Sex-Specific Transcriptional Profiles in Drosophila
title_fullStr Mitochondrial-Nuclear Interactions Mediate Sex-Specific Transcriptional Profiles in Drosophila
title_full_unstemmed Mitochondrial-Nuclear Interactions Mediate Sex-Specific Transcriptional Profiles in Drosophila
title_short Mitochondrial-Nuclear Interactions Mediate Sex-Specific Transcriptional Profiles in Drosophila
title_sort mitochondrial-nuclear interactions mediate sex-specific transcriptional profiles in drosophila
topic Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068850/
https://www.ncbi.nlm.nih.gov/pubmed/27558138
http://dx.doi.org/10.1534/genetics.116.192328
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