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dc.contributor.authorFarhat, Maha Ren_US
dc.contributor.authorShapiro, B Jesseen_US
dc.contributor.authorKieser, Karen Jen_US
dc.contributor.authorSultana, Razvanen_US
dc.contributor.authorJacobson, Karen Ren_US
dc.contributor.authorVictor, Thomas Cen_US
dc.contributor.authorWarren, Robin Men_US
dc.contributor.authorStreicher, Elizabeth Men_US
dc.contributor.authorCalver, Alistairen_US
dc.contributor.authorSloutsky, Alexen_US
dc.contributor.authorKaur, Devinderen_US
dc.contributor.authorPosey, Jamie Een_US
dc.contributor.authorPlikaytis, Bonnieen_US
dc.contributor.authorOggioni, Marco Ren_US
dc.contributor.authorGardy, Jennifer Len_US
dc.contributor.authorJohnston, James Cen_US
dc.contributor.authorRodrigues, Mabelen_US
dc.contributor.authorTang, Patrick K Cen_US
dc.contributor.authorKato-Maeda, Midorien_US
dc.contributor.authorBorowsky, Mark Len_US
dc.contributor.authorMuddukrishna, Bhavanaen_US
dc.contributor.authorKreiswirth, Barry Nen_US
dc.contributor.authorKurepina, Nataliaen_US
dc.contributor.authorGalagan, Jamesen_US
dc.contributor.authorGagneux, Sebastienen_US
dc.contributor.authorBirren, Bruceen_US
dc.contributor.authorRubin, Eric Jen_US
dc.contributor.authorLander, Eric Sen_US
dc.contributor.authorSabeti, Pardis Cen_US
dc.contributor.authorMurray, Meganen_US
dc.date.accessioned2014-05-06T16:16:57Z
dc.date.issued2013en_US
dc.identifier.citationFarhat, M. R., B. J. Shapiro, K. J. Kieser, R. Sultana, K. R. Jacobson, T. C. Victor, R. M. Warren, et al. 2013. “Genomic Analysis Identifies Targets of Convergent Positive Selection in Drug Resistant Mycobacterium tuberculosis.” Nature genetics 45 (10): 10.1038/ng.2747. doi:10.1038/ng.2747. http://dx.doi.org/10.1038/ng.2747.en
dc.identifier.issn1061-4036en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12152881
dc.description.abstractMycobacterium tuberculosis is successfully evolving antibiotic resistance, threatening attempts at tuberculosis epidemic control. Mechanisms of resistance, including the genetic changes favored by selection in resistant isolates, are incompletely understood. Using 116 newly and 7 previously sequenced M. tuberculosis genomes, we identified genomewide signatures of positive selection specific to the 47 resistant genomes. By searching for convergent evolution, the independent fixation of mutations at the same nucleotide site or gene, we recovered 100% of a set of known resistance markers. We also found evidence of positive selection in an additional 39 genomic regions in resistant isolates. These regions encode pathways of cell wall biosynthesis, transcriptional regulation and DNA repair. Mutations in these regions could directly confer resistance or compensate for fitness costs associated with resistance. Functional genetic analysis of mutations in one gene, ponA1, demonstrated an in vitro growth advantage in the presence of the drug rifampicin.en
dc.language.isoen_USen
dc.relation.isversionofdoi:10.1038/ng.2747en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887553/pdf/en
dash.licenseLAAen_US
dc.titleGenomic Analysis Identifies Targets of Convergent Positive Selection in Drug Resistant Mycobacterium tuberculosisen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNature geneticsen
dash.depositing.authorFarhat, Maha Ren_US
dc.date.available2014-05-06T16:16:57Z
dc.identifier.doi10.1038/ng.2747*
dash.authorsorderedfalse
dash.contributor.affiliatedBorowsky, Mark L
dash.contributor.affiliatedKieser, Karen
dash.contributor.affiliatedMurray, Megan
dash.contributor.affiliatedRubin, Eric
dash.contributor.affiliatedFarhat, Maha
dash.contributor.affiliatedSabeti, Pardis


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