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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis
Nature Genetics, Volume 45, No. 10, Year 2013
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Description
M. tuberculosis is evolving antibiotic resistance, threatening attempts at tuberculosis epidemic control. Mechanisms of resistance, including genetic changes favored by selection in resistant isolates, are incompletely understood. Using 116 newly sequenced and 7 previously sequenced M. tuberculosis whole genomes, we identified genome-wide signatures of positive selection specific to the 47 drug-resistant strains. By searching for convergent evolution - the independent fixation of mutations in the same nucleotide position 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 components in cell wall biosynthesis, transcriptional regulation and DNA repair pathways. 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. © 2013 Nature America, Inc. All rights reserved.
Authors & Co-Authors
Farhat, Maha Reda
Unknown Affiliation
Shapiro, B. Jesse
Unknown Affiliation
Kieser, Karen J.
Unknown Affiliation
Sultana, Razvan
Unknown Affiliation
Jacobson, Karen Rita
Unknown Affiliation
Victor, Thomas Calldo
Unknown Affiliation
Warren, Robin Mark
Unknown Affiliation
Streicher, Elizabeth Maria
Unknown Affiliation
Calver, Alistair D.
Unknown Affiliation
Sloutsky, Alex
Unknown Affiliation
Kaur, Devinder
Unknown Affiliation
Posey, James E.
Unknown Affiliation
Plikaytis, Bonnie B.
Unknown Affiliation
Oggioni, Marco R.
Unknown Affiliation
Gardy, Jennifer L.
Unknown Affiliation
Johnston, James Cameron
Unknown Affiliation
Rodrigues, Mabel
Unknown Affiliation
Tang, Patrick K.C.
Unknown Affiliation
Kato-Maeda, Midori
Unknown Affiliation
Borowsky, Mark L.
Unknown Affiliation
Muddukrishna, Bhavana
Unknown Affiliation
Kreiswirth, Barry N.
Unknown Affiliation
Kurepina, Natalia E.
Unknown Affiliation
Galagan, James E.
Unknown Affiliation
Gagneux, Sébastien P.
Unknown Affiliation
Birren, Bruce W.
Unknown Affiliation
Rubin, Eric Joseph
Unknown Affiliation
Lander, Eric S.
Unknown Affiliation
Sabeti., Pardis C.
Unknown Affiliation
Murray, Megan B.
Unknown Affiliation
Statistics
Citations: 401
Authors: 30
Affiliations: 21
Identifiers
Doi:
10.1038/ng.2747
ISSN:
10614036
e-ISSN:
15461718
Research Areas
Cancer
Genetics And Genomics