title: What cost mitochondria? The maintenance of functional mitochondrial DNA within and across generations.
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.
authors.affiliation: Laboratory of Genetics, Wageningen University, Droevendaalsesteeg 1, PO Box 309, 6700 AH Wageningen, The Netherlands duur.aanen@wur.nl.
authors.forename: Duur K
authors.initials: DK
authors.lastname: Aanen
authors.affiliation: Department of Pediatrics, Nijmegen Centre for Mitochondrial Disorders, Radboud University Medical Centre, Geert Grooteplein 10, PO Box 9101, 6500 HB Nijmegen, The Netherlands FinMIT Centre of Excellence, BioMediTech and Tampere University Hospital, Pirkanmaa Hospital District, 33014 Tampere, Finland.
authors.forename: Johannes N
authors.initials: JN
authors.lastname: Spelbrink
authors.affiliation: Behaviour and Genetics of Social Insects Lab, The University of Sydney, Sydney NSW 2006, Australia.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Beekman
mesh_terms: D000818:Animals; D005075:Biological Evolution; D004261:DNA Replication / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D008928:Mitochondria / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D004272:DNA, Mitochondrial
keywords: evolution; genetic conflict; mitochondria; mitochondrial DNA; mitochondrial disease