File(s) not publicly available
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 DowlingMitochondria 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 BiologyISSN
0960-9822Publisher
ElsevierExternal DOI
Issue
20Volume
25Page range
2717-2722Department affiliated with
- Evolution, Behaviour and Environment Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2016-01-15Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC