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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

journal contribution
posted on 2023-06-08, 23:59 authored by M Florencia Camus, Jochen B W Wolf, Ted Morrow, Damian K Dowling
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 and 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 organismal phenotype [2 and 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 mitochondrial 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.

History

Publication status

  • Published

Journal

Current Biology

ISSN

0960-9822

Publisher

Elsevier

Issue

20

Volume

25

Page range

2717-2722

Department affiliated with

  • Evolution, Behaviour and Environment Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2016-01-15

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