title: Regular bottlenecks and restrictions to somatic fusion prevent the accumulation of mitochondrial defects in Neurospora.
abstract: The replication and segregation of multi-copy mitochondrial DNA (mtDNA) are not under strict control of the nuclear DNA. Within-cell selection may thus favour variants with an intracellular selective advantage but a detrimental effect on cell fitness. High relatedness among the mtDNA variants of an individual is predicted to disfavour such deleterious selfish genetic elements, but experimental evidence for this hypothesis is scarce. We studied the effect of mtDNA relatedness on the opportunities for suppressive mtDNA variants in the fungus Neurospora carrying the mitochondrial mutator plasmid pKALILO. During growth, this plasmid integrates into the mitochondrial genome, generating suppressive mtDNA variants. These mtDNA variants gradually replace the wild-type mtDNA, ultimately culminating in growth arrest and death. We show that regular sequestration of mtDNA variation is required for effective selection against suppressive mtDNA variants. First, bottlenecks in the number of mtDNA copies from which a 'Kalilo' culture started significantly increased the maximum lifespan and variation in lifespan among cultures. Second, restrictions to somatic fusion among fungal individuals, either by using anastomosis-deficient mutants or by generating allotype diversity, prevented the accumulation of suppressive mtDNA variants. We discuss the implications of these results for the somatic accumulation of mitochondrial defects during ageing.
authors.affiliation: Laboratory of Genetics, Wageningen University, Droevendaalsesteeg 1, Wageningen 6708 PB, The Netherlands eric.bastiaans@wur.nl.
authors.forename: E
authors.initials: E
authors.lastname: Bastiaans
authors.affiliation: Laboratory of Genetics, Wageningen University, Droevendaalsesteeg 1, Wageningen 6708 PB, The Netherlands.
authors.forename: D K
authors.initials: DK
authors.lastname: Aanen
authors.affiliation: Laboratory of Genetics, Wageningen University, Droevendaalsesteeg 1, Wageningen 6708 PB, The Netherlands.
authors.forename: A J M
authors.initials: AJ
authors.lastname: Debets
authors.affiliation: Laboratory of Genetics, Wageningen University, Droevendaalsesteeg 1, Wageningen 6708 PB, The Netherlands.
authors.forename: R F
authors.initials: RF
authors.lastname: Hoekstra
authors.affiliation: Laboratory of Genetics, Wageningen University, Droevendaalsesteeg 1, Wageningen 6708 PB, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Lestrade
authors.affiliation: Laboratory of Genetics, Wageningen University, Droevendaalsesteeg 1, Wageningen 6708 PB, The Netherlands.
authors.forename: M F P M
authors.initials: MF
authors.lastname: Maas
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D004261:DNA Replication / Q000235:genetics / Q000502:physiology; D004272:DNA, Mitochondrial / Q000235:genetics / Q000502:physiology*; D014644:Genetic Variation; D008928:Mitochondria / Q000235:genetics / Q000502:physiology*; D016254:Mutagenesis, Insertional; D009491:Neurospora / Q000235:genetics / Q000502:physiology*; D012641:Selection, Genetic
chemical_list: D004272:DNA, Mitochondrial
keywords: anastomosis; kin selection; levels of selection; mitochondria; multi-level selection; senescence