Dataset Information

Mitonuclear Interactions Mediate Transcriptional Responses to Hypoxia in Drosophila.

ABSTRACT: Among the major challenges in quantitative genetics and personalized medicine is to understand how gene × gene interactions (G × G: epistasis) and gene × environment interactions (G × E) underlie phenotypic variation. Here, we use the intimate relationship between mitochondria and oxygen availability to dissect the roles of nuclear DNA (nDNA) variation, mitochondrial DNA (mtDNA) variation, hypoxia, and their interactions on gene expression in Drosophila melanogaster. Mitochondria provide an important evolutionary and medical context for understanding G × G and G × E given their central role in integrating cellular signals. We hypothesized that hypoxia would alter mitonuclear communication and gene expression patterns. We show that first order nDNA, mtDNA, and hypoxia effects vary between the sexes, along with mitonuclear epistasis and G × G × E effects. Females were generally more sensitive to genetic and environmental perturbation. While dozens to hundreds of genes are altered by hypoxia in individual genotypes, we found very little overlap among mitonuclear genotypes for genes that were significantly differentially expressed as a consequence of hypoxia; excluding the gene hairy. Oxidative phosphorylation genes were among the most influenced by hypoxia and mtDNA, and exposure to hypoxia increased the signature of mtDNA effects, suggesting retrograde signaling between mtDNA and nDNA. We identified nDNA-encoded genes in the electron transport chain (succinate dehydrogenase) that exhibit female-specific mtDNA effects. Our findings have important implications for personalized medicine, the sex-specific nature of mitonuclear communication, and gene × gene coevolution under variable or changing environments.

SUBMITTER: Mossman JA

PROVIDER: S-EPMC6095086 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mitonuclear Interactions Mediate Transcriptional Responses to Hypoxia in Drosophila.

Mossman Jim A JA Tross Jennifer G JG Jourjine Nick A NA Li Nan N Wu Zhijin Z Rand David M DM

Molecular biology and evolution 20170201 2

Among the major challenges in quantitative genetics and personalized medicine is to understand how gene × gene interactions (G × G: epistasis) and gene × environment interactions (G × E) underlie phenotypic variation. Here, we use the intimate relationship between mitochondria and oxygen availability to dissect the roles of nuclear DNA (nDNA) variation, mitochondrial DNA (mtDNA) variation, hypoxia, and their interactions on gene expression in Drosophila melanogaster. Mitochondria provide an impo ...[more]

PMID: 28110272

Similar Datasets

Project description:Mitochondrial function requires the coordinated expression of dozens of gene products from the mitochondrial genome and hundreds from the nuclear genomes. The systems that emerge from these interactions convert the food we eat and the oxygen we breathe into energy for life, while regulating a wide range of other cellular processes. These facts beg the question of whether the gene-by-gene interactions (G x G) that enable mitochondrial function are distinct from the gene-by-environment interactions (G x E) that fuel mitochondrial activity. We examine this question using a Drosophila model of mitonuclear interactions in which experimental combinations of mtDNA and nuclear chromosomes generate pairs of mitonuclear genotypes to test for epistatic interactions (G x G). These mitonuclear genotypes are then exposed to altered dietary or oxygen environments to test for G x E interactions. We use development time to assess dietary effects, and genome wide RNAseq analyses to assess hypoxic effects on transcription, which can be partitioned in to mito, nuclear, and environmental (G x G x E) contributions to these complex traits. We find that mitonuclear epistasis is universal, and that dietary and hypoxic treatments alter the epistatic interactions. We further show that the transcriptional response to alternative mitonuclear interactions has significant overlap with the transcriptional response to alternative oxygen environments. Gene coexpression analyses suggest that these shared genes are more central in networks of gene interactions, implying some functional overlap between epistasis and genotype by environment interactions. These results are discussed in the context of evolutionary fitness, the genetic basis of complex traits, and the challenge of achieving precision in personalized medicine. © 2018 The Authors. IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 70(12):1275-1288, 2018.

Dataset Information

Mitonuclear Interactions Mediate Transcriptional Responses to Hypoxia in Drosophila.

Publications

Mitonuclear Interactions Mediate Transcriptional Responses to Hypoxia in Drosophila.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets