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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.date.accessioned2022-03-07T09:38:20Z
dc.date.available2022-03-07T09:38:20Z
dc.date.created2022-01-15T10:17:31Z
dc.date.issued2021
dc.identifier.issn1544-9173
dc.identifier.urihttps://hdl.handle.net/11250/2983335
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.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleAvoiding organelle mutational meltdown across eukaryotes with or without a germline bottlenecken_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2021 Edwards et al.en_US
dc.source.articlenumbere3001153en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2
dc.identifier.doi10.1371/journal.pbio.3001153
dc.identifier.cristin1981709
dc.source.journalPLoS Biologyen_US
dc.relation.projectERC-European Research Council: 805046en_US
dc.identifier.citationPLoS Biology. 2021, 19 (4), e3001153.en_US
dc.source.volume19en_US
dc.source.issue4en_US


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