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Single Nucleotides in the mtDNA Sequence Modify Mitochondrial Molecular Function and Are Associated with Sex-Specific Effects on Fertility and Aging
Monash Univ, Sch Biol Sci, Clayton, Vic 3800, Australia..
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England..
Monash Univ, Sch Biol Sci, Clayton, Vic 3800, Australia..
2015 (English)In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 25, no 20, 2717-2722 p.Article in journal (Refereed) Published
Abstract [en]

Mitochondria underpin energy conversion in eukaryotes. Their small genomes have been the subject of increasing attention, and there is evidence that mitochondrial genetic variation can affect evolutionary trajectories and shape the expression of life-history traits considered to be key human health indicators [1, 2]. However, it is not understood how genetic variation across a diminutive genome, which in most species harbors only about a dozen protein-coding genes, can exert broad-scale effects on the organisnnal phenotype [2, 3]. Such effects are particularly puzzling given that the mitochondrial genes involved are under strong evolutionary constraint and that mitochondrial gene expression is highly conserved across diverse taxa [4]. We used replicated genetic lines in the fruit fly, Drosophila melanogaster, each characterized by a distinct and naturally occurring mitochondrial haplotype placed alongside an isogenic nuclear background. We demonstrate that sequence variation within the mitochondria! DNA (mtDNA) affects both the copy number of mitochondrial genomes and patterns of gene expression across key mitochondrial protein-coding genes. In several cases, haplotype-mediated patterns of gene expression were gene-specific, even for genes from within the same transcriptional units. This invokes post-transcriptional processing of RNA in the regulation of mitochondrial genetic effects on organismal phenotypes. Notably, the haplotype-mediated effects on gene expression could be traced backward to the level of individual nucleotides and forward to sex-specific effects on fertility and longevity. Our study thus elucidates how small-scale sequence changes in the mitochondrial genome can achieve broad-scale regulation of health-related phenotypes and even contribute to sex-related differences in longevity.

Place, publisher, year, edition, pages
2015. Vol. 25, no 20, 2717-2722 p.
National Category
Evolutionary Biology Genetics
URN: urn:nbn:se:uu:diva-267210DOI: 10.1016/j.cub.2015.09.012ISI: 000363359500031PubMedID: 26455309OAI: oai:DiVA.org:uu-267210DiVA: diva2:872472
EU, European Research Council, 280632
Available from: 2015-11-19 Created: 2015-11-19 Last updated: 2015-11-19Bibliographically approved

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