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dc.contributor.authorSankarasubramanian, Sankar
dc.date.accessioned2017-05-03T15:35:36Z
dc.date.available2017-05-03T15:35:36Z
dc.date.issued2011
dc.date.modified2012-07-02T05:49:44Z
dc.identifier.issn07374038
dc.identifier.doi10.1093/molbev/msr097
dc.identifier.urihttp://hdl.handle.net/10072/44247
dc.description.abstractDeleterious mutations associated with human diseases are predominantly found in conserved positions and positions that are essential for the structure and/or function of proteins. However, these mutations are purged from the human population over time and prevented from being fixed. Contrary to this belief, here I show that high proportions of deleterious amino acid changing mutations are fixed at positions critical for the structure and/or function of proteins. Similarly, a high rate of fixation of deleterious mutations was observed in slow-evolving amino acid positions of human proteins. The fraction of deleterious substitutions was found to be two times higher in relatively conserved amino acid positions than in highly variable positions. This study also found fixation of a much higher proportion of radical amino acid changes in primates compared with rodents and artiodactyls in slow-evolving positions. Previous studies observed a higher proportion of nonsynonymous substitutions in humans compared with other mammals, which was taken as indirect evidence for the fixation of deleterious mutations in humans. However, the results of this investigation provide direct evidence for this prediction by suggesting that the excess nonsynonymous mutations fixed in humans are indeed deleterious in nature. Furthermore, these results suggest that studies on disease-associated mutations should consider that a significant fraction of such deleterious mutations has already been fixed in the human genome, and thus, the effects of new mutations at those amino acid positions may not necessarily be deleterious and might even result in reversion to benign phenotypes.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent408577 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoen_US
dc.publisherOxford University Press
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom2687
dc.relation.ispartofpageto2693
dc.relation.ispartofissue9
dc.relation.ispartofjournalMolecular Biology and Evolution
dc.relation.ispartofvolume28
dc.rights.retentionY
dc.subject.fieldofresearchMolecular Evolution
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchEvolutionary Biology
dc.subject.fieldofresearchGenetics
dc.subject.fieldofresearchcode060409
dc.subject.fieldofresearchcode0601
dc.subject.fieldofresearchcode0603
dc.subject.fieldofresearchcode0604
dc.titleFixation of Deleterious Mutations at Critical Positions in Human Proteins
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Sciences, Griffith School of Environment
gro.rights.copyright© 2011 Oxford University Press. This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Molecular Biology and Evolution following peer review. The definitive publisher-authenticated version Fixation of Deleterious Mutations at Critical Positions inHuman Proteins, Molecular Biology and Evolution, (2011) 28 (9): 2687-2693 is available online at: http://dx.doi.org/10.1093/molbev/msr097
gro.date.issued2011
gro.hasfulltextFull Text
gro.griffith.authorSankarasubramanian, Sankar


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