Restricted Structural Gene Polymorphism in the Mycobacterium tuberculosis Complex Indicates Evolutionarily Recent Global Dissemination

One-third of humans are infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. Sequence analysis of two megabases in 26 structural genes or loci in strains recovered globally discovered a striking reduction of silent nucleotide substitutions compared with other human bacteria...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1997-09, Vol.94 (18), p.9869-9874
Main Authors: Sreevatsan, Srinand, Pan, Xi, Stockbauer, Kathryn E., Connell, Nancy D., Kreiswirth, Barry N., Whittam, Thomas S., Musser, James M.
Format: Article
Language:English
Subjects:
Alleles
Animals
Bacteria
Biological Evolution
Biological Sciences
Cattle
Codons
Evolution
Genes, Bacterial
Genetic variation
Genetics
Genomics
Humans
Mycobacterium tuberculosis
Mycobacterium tuberculosis - genetics
Nucleotides
Pathogens
Polymorphism, Genetic
Transposons
Tuberculosis
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Summary:One-third of humans are infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. Sequence analysis of two megabases in 26 structural genes or loci in strains recovered globally discovered a striking reduction of silent nucleotide substitutions compared with other human bacterial pathogens. The lack of neutral mutations in structural genes indicates that M. tuberculosis is evolutionarily young and has recently spread globally. Species diversity is largely caused by rapidly evolving insertion sequences, which means that mobile element movement is a fundamental process generating genomic variation in this pathogen. Three genetic groups of M. tuberculosis were identified based on two polymorphisms that occur at high frequency in the genes encoding catalase-peroxidase and the A subunit of gyrase. Group 1 organisms are evolutionarily old and allied with M. bovis, the cause of bovine tuberculosis. A subset of several distinct insertion sequence IS6110 subtypes of this genetic group have IS6110 integrated at the identical chromosomal insertion site, located between dnaA and dnaN in the region containing the origin of replication. Remarkably, study of ≈ 6,000 isolates from patients in Houston and the New York City area discovered that 47 of 48 relatively large case clusters were caused by genotypic group 1 and 2 but not group 3 organisms. The observation that the newly emergent group 3 organisms are associated with sporadic rather than clustered cases suggests that the pathogen is evolving toward a state of reduced transmissability or virulence.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.94.18.9869