What cost mitochondria? The maintenance of functional mitochondrial DNA within and across generations

D.K. Aanen, J.N. Spelbrink, M. Beekman

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Scopus)

Abstract

The peculiar biology of mitochondrial DNA (mtDNA) potentially has detrimental consequences for organismal health and lifespan. Typically, eukaryotic cells contain multiple mitochondria, each with multiple mtDNA genomes. The high copy number of mtDNA implies that selection on mtDNA functionality is relaxed. Furthermore, because mtDNA replication is not strictly regulated, within-cell selection may favour mtDNA variants with a replication advantage, but a deleterious effect on cell fitness. The opportunities for selfish mtDNA mutations to spread are restricted by various organism-level adaptations, such as uniparental transmission, germline mtDNA bottlenecks, germline selection and, during somatic growth, regular alternation between fusion and fission of mitochondria. These mechanisms are all hypothesized to maintain functional mtDNA. However, the strength of selection for maintenance of functional mtDNA progressively declines with age, resulting in age-related diseases. Furthermore, organismal adaptations that most probably evolved to restrict the opportunities for selfish mtDNA create secondary problems. Owing to predominantly maternal mtDNA transmission, recombination among mtDNA from different individuals is highly restricted or absent, reducing the scope for repair. Moreover, maternal inheritance precludes selection against mtDNA variants with male-specific effects. We finish by discussing the consequences of life-history differences among taxa with respect to mtDNA evolution and make a case for the use of microorganisms to experimentally manipulate levels of selection
Original languageEnglish
JournalPhilosophical Transactions of the Royal Society B. Biological sciences
Volume369
Issue number1646
DOIs
Publication statusPublished - 2014

Keywords

  • hereditary optic neuropathy
  • cytoplasmic inheritance
  • deletion mutants
  • evolution
  • mtdna
  • mutations
  • selection
  • disease
  • genomes
  • accumulation

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