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TitleEvidence for diversifying selection in a set of Mycobacterium tuberculosis genes in response to Antibiotic- and Nonantibiotic- related pressure
Author(s)Osório, Nuno S.
Rodrigues, Fernando
Gagneux, Sebastien
Pedrosa, Jorge
Pinto-Carbó, Marta
Castro, António G.
Young, Douglas
Comas, Iñaki
Saraiva, Margarida
KeywordsDiversifying selection
Positive selection
Mycobacterium, tuberculosis
Genetic diversity
Computational molecular biology
Drug resistance
Issue dateJun-2013
PublisherOxford University Press
JournalMolecular Biology and Evolution
Abstract(s)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.
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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