Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/40675

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dc.contributor.authorCavadas, Brunopor
dc.contributor.authorSoares, Pedropor
dc.contributor.authorCamacho, Ruipor
dc.contributor.authorBrandão, Andreiapor
dc.contributor.authorCosta, Marta Dpor
dc.contributor.authorFernandes, Verónicapor
dc.contributor.authorPereira, Joana Bpor
dc.contributor.authorRito, Teresa Spor
dc.contributor.authorSamuels, David Cpor
dc.contributor.authorPereira, Luisapor
dc.date.accessioned2016-03-07T09:43:59Z-
dc.date.issued2015-11-
dc.identifier.citationCavadas, B., Soares, P., Camacho, R., Brandão, A., Costa, M. D., Fernandes, V., . . . Pereira, L. (2015). Fine Time Scaling of Purifying Selection on Human Nonsynonymous mtDNA Mutations Based on the Worldwide Population Tree and Mother-Child Pairs. Human Mutation, 36(11), 1100-1111. doi: 10.1002/humu.22849por
dc.identifier.issn1059-7794por
dc.identifier.urihttp://hdl.handle.net/1822/40675-
dc.description.abstractA high-resolution mtDNA phylogenetic tree allowed us to look backward in time to investigate purifying selection. Purifying selection was very strong in the last 2,500 years, continuously eliminating pathogenic mutations back until the end of the Younger Dryas (∼11,000 years ago), when a large population expansion likely relaxed selection pressure. This was preceded by a phase of stable selection until another relaxation occurred in the out-of-Africa migration. Demography and selection are closely related: expansions led to relaxation of selection and higher pathogenicity mutations significantly decreased the growth of descendants. The only detectible positive selection was the recurrence of highly pathogenic nonsynonymous mutations (m.3394T>C-m.3397A>G-m.3398T>C) at interior branches of the tree, preventing the formation of a dinucleotide STR (TATATA) in the MT-ND1 gene. At the most recent time scale in 124 mother-children transmissions, purifying selection was detectable through the loss of mtDNA variants with high predicted pathogenicity. A few haplogroup-defining sites were also heteroplasmic, agreeing with a significant propensity in 349 positions in the phylogenetic tree to revert back to the ancestral variant. This nonrandom mutation property explains the observation of heteroplasmic mutations at some haplogroup-defining sites in sequencing datasets, which may not indicate poor quality as has been claimed.por
dc.description.sponsorshipContract grant sponsors: FCT, the Portuguese Foundation for Science and Technology (PTDC/IVC-ANT/4917/2012, SFRH/BD/78990/2011, and IF/01641/2013); FEDER, COMPETE, and FCT (FCOMP-01-0124-FEDER-029291, PEst-C/SAU/LA0003/2013, and PEst-OE/BIA/UI4050/2014); Luso American Foundation (FLAD).por
dc.language.isoengpor
dc.publisherWiley-
dc.relationinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/132046/PTpor
dc.relationinfo:eu-repo/grantAgreement/FCT/COMPETE/132983/PTpor
dc.relationinfo:eu-repo/grantAgreement/FCT/5876/135919/PTpor
dc.relationSFRH/BD/78990/2011por
dc.rightsrestrictedAccesspor
dc.subjectmtDNApor
dc.subjectWorldwide phylogenetic treepor
dc.subjectMother–child pairspor
dc.subjectMassive parallel sequencingpor
dc.subjectHeteroplasmypor
dc.titleFine time scaling of purifying selection on human nonsynonymous mtDNA mutations based on the worldwide population tree and mother-child pairspor
dc.typearticlepor
dc.peerreviewedyespor
sdum.publicationstatuspublishedpor
oaire.citationStartPage1100por
oaire.citationEndPage1111por
oaire.citationIssue11por
oaire.citationTitleHuman mutationpor
oaire.citationVolume36por
dc.identifier.doi10.1002/humu.22849por
dc.identifier.pmid26252938por
dc.subject.fosCiências Naturais::Ciências Biológicaspor
dc.subject.wosScience & Technologypor
sdum.journalHuman mutationpor
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