Lethal Interaction of Nuclear and Mitochondrial Genotypes in Drosophila melanogaster.
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ABSTRACT:
SUBMITTER: Salminen TS
PROVIDER: S-EPMC6643882 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
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Project description:BackgroundMitochondria are organelles found in nearly all eukaryotic cells that play a crucial role in cellular survival and function. Mitochondrial function is under the control of nuclear and mitochondrial genomes. While the latter has been the focus of most genetic research, we remain largely ignorant about the nuclear-encoded genomic control of inter-individual variability in mitochondrial function. Here, we used Drosophila melanogaster as our model organism to address this question.ResultsWe quantified mitochondrial state 3 and state 4 respiration rates and P:O ratio in mitochondria isolated from the thoraces of 40 sequenced inbred lines of the Drosophila Genetic Reference Panel. We found significant within-population genetic variability for all mitochondrial traits. Hence, we performed genome-wide association mapping and identified 141 single nucleotide polymorphisms (SNPs) associated with differences in mitochondrial respiration and efficiency (P ≤1 × 10-5). Gene-centered regression models showed that 2-3 SNPs can explain 31, 13, and 18% of the phenotypic variation in state 3, state 4, and P:O ratio, respectively. Most of the genes tagged by the SNPs are involved in organ development, second messenger-mediated signaling pathways, and cytoskeleton remodeling. One of these genes, sallimus (sls), encodes a component of the muscle sarcomere. We confirmed the direct effect of sls on mitochondrial respiration using two viable mutants and their coisogenic wild-type strain. Furthermore, correlation network analysis revealed that sls functions as a transcriptional hub in a co-regulated module associated with mitochondrial respiration and is connected to CG7834, which is predicted to encode a protein with mitochondrial electron transfer flavoprotein activity. This latter finding was also verified in the sls mutants.ConclusionsOur results provide novel insights into the genetic factors regulating natural variation in mitochondrial function in D. melanogaster. The integrative genomic approach used in our study allowed us to identify sls as a novel hub gene responsible for the regulation of mitochondrial respiration in muscle sarcomere and to provide evidence that sls might act via the electron transfer flavoprotein/ubiquinone oxidoreductase complex.
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Project description:Maternally inherited microorganisms can influence the mtDNA pattern of variation in hosts. This influence is driven by selection among symbionts and can cause the frequency of mitochondrial variants in the population to eventually increase or decrease. Wolbachia infection is common and widespread in Drosophila melanogaster populations. We compared genetic variability of D. melanogaster mitotypes with Wolbachia genotypes among isofemale lines associated with different geographic locations and time intervals to study coevolution of the mtDNA and Wolbachia. Phylogenetic analysis of D. melanogaster mtDNA revealed two clades diverged in Africa, each associated with one of the two Wolbachia genotype groups. No evidence of horizontal transmission of Wolbachia between maternal lineages has been found. All the mtDNA variants that occur in infected isofemale lines are found in uninfected isofemale lines and vice versa, which is indicative of a recent loss of infection from some maternal fly lineages and confirms a significant role of Wolbachia in the D. melanogaster mtDNA pattern of variation. Finally, we present a comparative analysis of biogeographic distribution of D. melanogaster mitotypes all over the world.
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Project description:All 37 mitochondrial DNA (mtDNA)-encoded genes involved with oxidative phosphorylation and intramitochondrial protein synthesis, and several nuclear-encoded genes involved with mtDNA replication, transcription, repair and recombination are conserved between the fruit fly Drosophila melanogaster and mammals. This, in addition to its easy genetic tractability, has made Drosophila a useful model for our understanding of animal mtDNA maintenance and human mtDNA diseases. However, there are key differences between the Drosophila and mammalian systems that feature the diversity of mtDNA maintenance processes inside animal cells. Here, we review what is known about mtDNA maintenance in Drosophila, highlighting areas for which more research is warranted and providing a perspective preliminary in silico and in vivo analyses of the tissue specificity of mtDNA maintenance processes in this model organism. Our results suggest new roles (or the lack thereof) for well-known maintenance proteins, such as the helicase Twinkle and the accessory subunit of DNA polymerase γ, and for other Drosophila gene products that may even aid in shedding light on mtDNA maintenance in other animals. We hope to provide the reader some interesting paths that can be taken to help our community show how Drosophila may impact future mtDNA maintenance research.
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2011-05-05 | PRD000255 | Pride