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PMID: 15498158 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Silent nucleotide polymorphisms and a phylogeny for Mycobacterium tuberculosis.

Emerging infectious diseases ·Vol. 10 ·No. 9 ·2004-09-00 ·Pages 1568-77

Baker L, Brown T, Maiden MC, Drobniewski F

Abstract

Much remains unknown of the phylogeny and evolution of Mycobacterium tuberculosis, an organism that kills 2 million people annually. Using a population-based approach that analyzes multiple loci around the chromosome, we demonstrate that neutral genetic variation in genes associated with antimicrobial drug resistance has sufficient variation to construct a robust phylogenetic tree for M. tuberculosis. The data describe a clonal population with a minimum of four distinct M. tuberculosis lineages, closely related to M. bovis. The lineages are strongly geographically associated. Nucleotide substitutions proven to cause drug resistance are distributed throughout the tree, whereas nonsynonymous base substitutions unrelated to drug resistance have a restricted distribution. The phylogenetic structure is concordant with all the previously described genotypic and phenotypic groupings of M. tuberculosis strains and provides a unifying framework for both epidemiologic and evolutionary analysis of M. tuberculosis populations.

MeSH Terms
Amidohydrolases/genetics Antitubercular Agents/pharmacology Bacterial Proteins/genetics Base Sequence Catalase/genetics DNA Fingerprinting DNA Gyrase/genetics DNA-Directed RNA Polymerases/genetics Drug Resistance, Multiple, Bacterial/genetics Evolution, Molecular Genetic Variation Molecular Sequence Data Mycobacterium tuberculosis/genetics Phylogeny Polymorphism, Single Nucleotide Ribosomal Proteins/genetics Sequence Alignment Sequence Analysis, DNA
Chemicals
Antitubercular Agents Bacterial Proteins Ribosomal Proteins Catalase katG protein, Mycobacterium tuberculosis DNA-Directed RNA Polymerases RNA polymerase beta subunit Amidohydrolases PncA protein, Mycobacterium tuberculosis DNA Gyrase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Baker Lucy
Health Protection Agency, London, United Kingdom.
Brown Tim
Maiden Martin C
Drobniewski Francis
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Article Info
Journal
Emerging infectious diseases
Abbr.
Emerg Infect Dis
ISSN
1080-6040
DOI
10.3201/eid1009.040046
Published
2004-09-00
Pages
1568-77
Language
English
Region
United States
NLM ID
9508155
PMCID
PMC3320301
Subset
IM
External Links
PubMed source DOI: 10.3201/eid1009.040046 PMC Full Text View journal details
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