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Evidence for diversifying selection in a set of Mycobacterium tuberculosis genes in response to antibiotic- and nonantibiotic-related pressure

Osório, Nuno S. and Rodrigues, Fernando and Gagneux, Sebastien and Pedrosa, Jorge and Pinto-Carbó, Marta and Castro, António G. and Young, Douglas and Comas, Iñaki and Saraiva, Margarida. (2013) Evidence for diversifying selection in a set of Mycobacterium tuberculosis genes in response to antibiotic- and nonantibiotic-related pressure. Molecular biology and evolution, Vol. 30, no. 6. pp. 1326-1336.

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Official URL: http://edoc.unibas.ch/dok/A6165037

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Abstract

Tuberculosis (TB) is a global health problem estimated to kill 1.4 million people per year. Recent advances in the genomics of the causative agents of TB, bacteria known as the Mycobacterium tuberculosis complex (MTBC), have allowed a better comprehension of its population structure and provided the foundation for molecular evolution analyses. These studies are crucial for a better understanding of TB, including the variation of vaccine efficacy and disease outcome, together with the emergence of drug resistance. Starting from the analysis of 73 publicly available genomes from all the main MTBC lineages, we have screened for evidences of positive selection, a set of 576 genes previously associated with drug resistance or encoding membrane proteins. As expected, because antibiotics constitute strong selective pressure, some of the codons identified correspond to the position of confirmed drug-resistance-associated substitutions in the genes embB, rpoB, and katG. Furthermore, we identified diversifying selection in specific codons of the genes Rv0176 and Rv1872c coding for MCE1-associated transmembrane protein and a putative l-lactate dehydrogenase, respectively. Amino acid sequence analyses showed that in Rv0176, sites undergoing diversifying selection were in a predicted antigen region that varies between "modern" lineages and "ancient" MTBC/BCG strains. In Rv1872c, some of the sites under selection are predicted to impact protein function and thus might result from metabolic adaptation. These results illustrate that diversifying selection in MTBC is happening as a consequence of both antibiotic treatment and other evolutionary pressures.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Research (Gagneux)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Gagneux, Sebastien
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Oxford University Press
ISSN:0737-4038
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 Feb 2014 15:46
Deposited On:27 Feb 2014 15:46

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