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dc.contributor.authorRøyrvik, Ellen Christine
dc.contributor.authorJohnston, Iain
dc.date.accessioned2021-08-06T09:15:04Z
dc.date.available2021-08-06T09:15:04Z
dc.date.created2020-09-23T00:34:26Z
dc.date.issued2020
dc.identifier.issn0305-1048
dc.identifier.urihttps://hdl.handle.net/11250/2766750
dc.description.abstractMitochondrial DNA (mtDNA) encodes cellular machinery vital for cell and organism survival. Mutations, genetic manipulation, and gene therapies may produce cells where different types of mtDNA coexist in admixed populations. In these admixtures, one mtDNA type is often observed to proliferate over another, with different types dominating in different tissues. This ‘segregation bias’ is a long-standing biological mystery that may pose challenges to modern mtDNA disease therapies, leading to substantial recent attention in biological and medical circles. Here, we show how an mtDNA sequence’s balance between replication and transcription, corresponding to molecular ‘selfishness’, in conjunction with cellular selection, can potentially modulate segregation bias. We combine a new replication-transcription-selection (RTS) model with a meta-analysis of existing data to show that this simple theory predicts complex tissue-specific patterns of segregation in mouse experiments, and reversion in human stem cells. We propose the stability of G-quadruplexes in the mtDNA control region, influencing the balance between transcription and replication primer formation, as a potential molecular mechanism governing this balance. Linking mtDNA sequence features, through this molecular mechanism, to cellular population dynamics, we use sequence data to obtain and verify the sequence-specific predictions from this hypothesis on segregation behaviour in mouse and human mtDNA.en_US
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleMtDNA sequence features associated with 'selfish genomes' predict tissue-specific segregation and reversionen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2020 The Authorsen_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2
dc.identifier.doi10.1093/nar/gkaa622
dc.identifier.cristin1832324
dc.source.journalNucleic Acids Research (NAR)en_US
dc.source.pagenumber8290-8301en_US
dc.identifier.citationNucleic Acids Research (NAR). 2020, 48 (15), 8290-8301.en_US
dc.source.volume48en_US
dc.source.issue15en_US


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