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dc.contributor.authorEdwards, David
dc.contributor.authorRøyrvik, Ellen Christine
dc.contributor.authorChustecki, Joanne
dc.contributor.authorGiannakis, Konstantinos
dc.contributor.authorGlastad, Robert Clay
dc.contributor.authorRadzvilavicius, Arunas
dc.contributor.authorJohnston, Iain
dc.description.abstractMitochondrial DNA (mtDNA) and plastid DNA (ptDNA) encode vital bioenergetic apparatus, and mutations in these organelle DNA (oDNA) molecules can be devastating. In the germline of several animals, a genetic “bottleneck” increases cell-to-cell variance in mtDNA heteroplasmy, allowing purifying selection to act to maintain low proportions of mutant mtDNA. However, most eukaryotes do not sequester a germline early in development, and even the animal bottleneck remains poorly understood. How then do eukaryotic organelles avoid Muller’s ratchet—the gradual buildup of deleterious oDNA mutations? Here, we construct a comprehensive and predictive genetic model, quantitatively describing how different mechanisms segregate and decrease oDNA damage across eukaryotes. We apply this comprehensive theory to characterise the animal bottleneck with recent single-cell observations in diverse mouse models. Further, we show that gene conversion is a particularly powerful mechanism to increase beneficial cell-to-cell variance without depleting oDNA copy number, explaining the benefit of observed oDNA recombination in diverse organisms which do not sequester animal-like germlines (for example, sponges, corals, fungi, and plants). Genomic, transcriptomic, and structural datasets across eukaryotes support this mechanism for generating beneficial variance without a germline bottleneck. This framework explains puzzling oDNA differences across taxa, suggesting how Muller’s ratchet is avoided in different eukaryotes.en_US
dc.publisherPublic Library of Scienceen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleAvoiding organelle mutational meltdown across eukaryotes with or without a germline bottlenecken_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCopyright 2021 Edwards et al.en_US
dc.source.journalPLoS Biologyen_US
dc.relation.projectERC-European Research Council: 805046en_US
dc.identifier.citationPLoS Biology. 2021, 19 (4), e3001153.en_US

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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal