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

Detalhes bibliográficos
Autor(a) principal: Osório, Nuno S.
Data de Publicação: 2013
Outros Autores: Rodrigues, Fernando, Gagneux, Sebastien, Pedrosa, Jorge, Pinto-Carbó, Marta, Castro, António G., Young, Douglas, Comas, Iñaki, Saraiva, Margarida
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/24246
Resumo: 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.
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spelling Evidence for diversifying selection in a set of Mycobacterium tuberculosis genes in response to Antibiotic- and Nonantibiotic- related pressureDiversifying selectionPositive selectionMycobacterium, tuberculosisGenetic diversityComputational molecular biologyEvolutionPhylogenyDrug resistanceGenomicsMycobacteriumtuberculosisScience & TechnologyTuberculosis (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.N.S.O. is supported by the Portuguese Foundation for Science and Technology (FCT) SFRH/BPD/33959/2009, and M.S. is a Ciência 2007 Fellow. I.C. is supported by Marie Curie FP7 action 272086. This work was partially supported by Ministerio de Economia y Competitividad (MINECO), Spain, project BFU2011-24112.Oxford University PressUniversidade do MinhoOsório, Nuno S.Rodrigues, FernandoGagneux, SebastienPedrosa, JorgePinto-Carbó, MartaCastro, António G.Young, DouglasComas, IñakiSaraiva, Margarida2013-062013-06-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/24246eng0737-403810.1093/molbev/mst03823449927info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:41:14Zoai:repositorium.sdum.uminho.pt:1822/24246Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:38:09.409343Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Evidence for diversifying selection in a set of Mycobacterium tuberculosis genes in response to Antibiotic- and Nonantibiotic- related pressure
title Evidence for diversifying selection in a set of Mycobacterium tuberculosis genes in response to Antibiotic- and Nonantibiotic- related pressure
spellingShingle Evidence for diversifying selection in a set of Mycobacterium tuberculosis genes in response to Antibiotic- and Nonantibiotic- related pressure
Osório, Nuno S.
Diversifying selection
Positive selection
Mycobacterium, tuberculosis
Genetic diversity
Computational molecular biology
Evolution
Phylogeny
Drug resistance
Genomics
Mycobacterium
tuberculosis
Science & Technology
title_short Evidence for diversifying selection in a set of Mycobacterium tuberculosis genes in response to Antibiotic- and Nonantibiotic- related pressure
title_full Evidence for diversifying selection in a set of Mycobacterium tuberculosis genes in response to Antibiotic- and Nonantibiotic- related pressure
title_fullStr Evidence for diversifying selection in a set of Mycobacterium tuberculosis genes in response to Antibiotic- and Nonantibiotic- related pressure
title_full_unstemmed Evidence for diversifying selection in a set of Mycobacterium tuberculosis genes in response to Antibiotic- and Nonantibiotic- related pressure
title_sort Evidence for diversifying selection in a set of Mycobacterium tuberculosis genes in response to Antibiotic- and Nonantibiotic- related pressure
author Osório, Nuno S.
author_facet Osório, Nuno S.
Rodrigues, Fernando
Gagneux, Sebastien
Pedrosa, Jorge
Pinto-Carbó, Marta
Castro, António G.
Young, Douglas
Comas, Iñaki
Saraiva, Margarida
author_role author
author2 Rodrigues, Fernando
Gagneux, Sebastien
Pedrosa, Jorge
Pinto-Carbó, Marta
Castro, António G.
Young, Douglas
Comas, Iñaki
Saraiva, Margarida
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Osório, Nuno S.
Rodrigues, Fernando
Gagneux, Sebastien
Pedrosa, Jorge
Pinto-Carbó, Marta
Castro, António G.
Young, Douglas
Comas, Iñaki
Saraiva, Margarida
dc.subject.por.fl_str_mv Diversifying selection
Positive selection
Mycobacterium, tuberculosis
Genetic diversity
Computational molecular biology
Evolution
Phylogeny
Drug resistance
Genomics
Mycobacterium
tuberculosis
Science & Technology
topic Diversifying selection
Positive selection
Mycobacterium, tuberculosis
Genetic diversity
Computational molecular biology
Evolution
Phylogeny
Drug resistance
Genomics
Mycobacterium
tuberculosis
Science & Technology
description 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.
publishDate 2013
dc.date.none.fl_str_mv 2013-06
2013-06-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/24246
url http://hdl.handle.net/1822/24246
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0737-4038
10.1093/molbev/mst038
23449927
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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