IDT. Quality oligos. Every time.

Genetics, Vol. 162, 1533-1543, December 2002, Copyright © 2002

Genome-Wide Analysis of Synonymous Single Nucleotide Polymorphisms in Mycobacterium tuberculosis Complex Organisms: Resolution of Genetic Relationships Among Closely Related Microbial Strains

Michaela M. Gutackera, James C. Smoota, Cristi A. Lux Migliaccioa, Stacy M. Ricklefsa, Su Huaa, Debby V. Cousinsb, Edward A. Gravissc, Elena Shashkinad, Barry N. Kreiswirthd, and James M. Mussera
a Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840,
b Department of Agriculture, Australian Reference Laboratory for Bovine Tuberculosis, South Perth 6151, Australia,
c Department of Pathology, Baylor College of Medicine, Houston, Texas 77030
d Public Health Research Institute Tuberculosis Center, New York, New York 10016

Corresponding author: James M. Musser, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840., jmusser{at}niaid.nih.gov (E-mail)

Communicating editor: Y.-X. FU

Several human pathogens (e.g., Bacillus anthracis, Yersinia pestis, Bordetella pertussis, Plasmodium falciparum, and Mycobacterium tuberculosis) have very restricted unselected allelic variation in structural genes, which hinders study of the genetic relationships among strains and strain-trait correlations. To address this problem in a representative pathogen, 432 M. tuberculosis complex strains from global sources were genotyped on the basis of 230 synonymous (silent) single nucleotide polymorphisms (sSNPs) identified by comparison of four genome sequences. Eight major clusters of related genotypes were identified in M. tuberculosis sensu stricto, including a single cluster representing organisms responsible for several large outbreaks in the United States and Asia. All M. tuberculosis sensu stricto isolates of previously unknown phylogenetic position could be rapidly and unambiguously assigned to one of the eight major clusters, thus providing a facile strategy for identifying organisms that are clonally related by descent. Common clones of M. tuberculosis sensu stricto and M. bovis are distinct, deeply branching genotypic complexes whose extant members did not emerge directly from one another in the recent past. sSNP genotyping rapidly delineates relationships among closely related strains of pathogenic microbes and allows construction of genetic frameworks for examining the distribution of biomedically relevant traits such as virulence, transmissibility, and host range.




This article has been cited by other articles:


Home page
 J. Mol. Diagn.Home page
C. Z. Grimes, L. D. Teeter, L.-Y. Hwang, and E. A. Graviss
Epidemiologic Characterization of Culture Positive Mycobacterium tuberculosis Patients by katG-gyrA Principal Genetic Grouping
J. Mol. Diagn., September 1, 2009; 11(5): 472 - 481.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
V. Mathys, R. Wintjens, P. Lefevre, J. Bertout, A. Singhal, M. Kiass, N. Kurepina, X.-M. Wang, B. Mathema, A. Baulard, et al.
Molecular Genetics of para-Aminosalicylic Acid Resistance in Clinical Isolates and Spontaneous Mutants of Mycobacterium tuberculosis
Antimicrob. Agents Chemother., May 1, 2009; 53(5): 2100 - 2109.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
N. Mackenzie, D. C. Alexander, C. Y. Turenne, M. A. Behr, and J. M. De Buck
Genomic Comparison of PE and PPE Genes in the Mycobacterium avium Complex
J. Clin. Microbiol., April 1, 2009; 47(4): 1002 - 1011.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
B. Muller, M. Hilty, S. Berg, M. C. Garcia-Pelayo, J. Dale, M. L. Boschiroli, S. Cadmus, B. N. R. Ngandolo, S. Godreuil, C. Diguimbaye-Djaibe, et al.
African 1, an Epidemiologically Important Clonal Complex of Mycobacterium bovis Dominant in Mali, Nigeria, Cameroon, and Chad
J. Bacteriol., March 15, 2009; 191(6): 1951 - 1960.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
D. Sinsimer, G. Huet, C. Manca, L. Tsenova, M.-S. Koo, N. Kurepina, B. Kana, B. Mathema, S. A. E. Marras, B. N. Kreiswirth, et al.
The Phenolic Glycolipid of Mycobacterium tuberculosis Differentially Modulates the Early Host Cytokine Response but Does Not in Itself Confer Hypervirulence
Infect. Immun., July 1, 2008; 76(7): 3027 - 3036.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
C. Y. Turenne, D. M. Collins, D. C. Alexander, and M. A. Behr
Mycobacterium avium subsp. paratuberculosis and M. avium subsp. avium Are Independently Evolved Pathogenic Clones of a Much Broader Group of M. avium Organisms
J. Bacteriol., April 1, 2008; 190(7): 2479 - 2487.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
A. L. Gibson, R. C. Huard, N. C. Gey van Pittius, L. C. O. Lazzarini, J. Driscoll, N. Kurepina, T. Zozio, C. Sola, S. M. Spindola, A. L. Kritski, et al.
Application of Sensitive and Specific Molecular Methods To Uncover Global Dissemination of the Major RDRio Sublineage of the Latin American-Mediterranean Mycobacterium tuberculosis Spoligotype Family
J. Clin. Microbiol., April 1, 2008; 46(4): 1259 - 1267.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
T. A. Griffiths, K. Rioux, and J. De Buck
Sequence Polymorphisms in a Surface PPE Protein Distinguish Types I, II, and III of Mycobacterium avium subsp. paratuberculosis
J. Clin. Microbiol., April 1, 2008; 46(4): 1207 - 1212.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. D. Kennedy, M. Otto, K. R. Braughton, A. R. Whitney, L. Chen, B. Mathema, J. R. Mediavilla, K. A. Byrne, L. D. Parkins, F. C. Tenover, et al.
From the Cover: Epidemic community-associated methicillin-resistant Staphylococcus aureus: Recent clonal expansion and diversification
PNAS, January 29, 2008; 105(4): 1327 - 1332.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
S. Octavia and R. Lan
Single-Nucleotide-Polymorphism Typing and Genetic Relationships of Salmonella enterica Serovar Typhi Isolates
J. Clin. Microbiol., November 1, 2007; 45(11): 3795 - 3801.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
Y. Kong, M. D. Cave, L. Zhang, B. Foxman, C. F. Marrs, J. H. Bates, and Z. H. Yang
Association between Mycobacterium tuberculosis Beijing/W Lineage Strain Infection and Extrathoracic Tuberculosis: Insights from Epidemiologic and Clinical Characterization of the Three Principal Genetic Groups of M. tuberculosis Clinical Isolates
J. Clin. Microbiol., February 1, 2007; 45(2): 409 - 414.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
X. Liu, M. M. Gutacker, J. M. Musser, and Y.-X. Fu
Evidence for Recombination in Mycobacterium tuberculosis
J. Bacteriol., December 1, 2006; 188(23): 8169 - 8177.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
Y. Kong, M. D. Cave, L. Zhang, B. Foxman, C. F. Marrs, J. H. Bates, and Z. H. Yang
Population-Based Study of Deletions in Five Different Genomic Regions of Mycobacterium tuberculosis and Possible Clinical Relevance of the Deletions
J. Clin. Microbiol., November 1, 2006; 44(11): 3940 - 3946.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Microbiol. Rev.Home page
B. Mathema, N. E. Kurepina, P. J. Bifani, and B. N. Kreiswirth
Molecular Epidemiology of Tuberculosis: Current Insights
Clin. Microbiol. Rev., October 1, 2006; 19(4): 658 - 685.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
N. B. Harris, J. B. Payeur, V. Kapur, and S. Sreevatsan
Short-Sequence-Repeat Analysis of Mycobacterium avium subsp. paratuberculosis and Mycobacterium avium subsp. avium Isolates Collected from Animals Throughout the United States Reveals Both Stability of Loci and Extensive Diversity
J. Clin. Microbiol., August 1, 2006; 44(8): 2970 - 2973.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Microbiol. Rev.Home page
D. F. Warner and V. Mizrahi
Tuberculosis Chemotherapy: the Influence of Bacillary Stress and Damage Response Pathways on Drug Efficacy
Clin. Microbiol. Rev., July 1, 2006; 19(3): 558 - 570.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
R. C. Huard, M. Fabre, P. de Haas, L. Claudio Oliveira Lazzarini, D. van Soolingen, D. Cousins, and J. L. Ho
Novel Genetic Polymorphisms That Further Delineate the Phylogeny of the Mycobacterium tuberculosis Complex
J. Bacteriol., June 15, 2006; 188(12): 4271 - 4287.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
E. Pagan-Ramos, S. S. Master, C. L. Pritchett, R. Reimschuessel, M. Trucksis, G. S. Timmins, and V. Deretic
Molecular and Physiological Effects of Mycobacterial oxyR Inactivation
J. Bacteriol., April 1, 2006; 188(7): 2674 - 2680.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
H. Hu, R. Lan, and P. R. Reeves
Adaptation of Multilocus Sequencing for Studying Variation Within a Major Clone: Evolutionary Relationships of Salmonella enterica Serovar Typhimurium
Genetics, February 1, 2006; 172(2): 743 - 750.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
I. Filliol, A. S. Motiwala, M. Cavatore, W. Qi, M. H. Hazbon, M. Bobadilla del Valle, J. Fyfe, L. Garcia-Garcia, N. Rastogi, C. Sola, et al.
Global Phylogeny of Mycobacterium tuberculosis Based on Single Nucleotide Polymorphism (SNP) Analysis: Insights into Tuberculosis Evolution, Phylogenetic Accuracy of Other DNA Fingerprinting Systems, and Recommendations for a Minimal Standard SNP Set
J. Bacteriol., January 15, 2006; 188(2): 759 - 772.
[Abstract] [Full Text] [PDF]

Home page
 Appl. Environ. Microbiol.Home page
A. Gibson, T. Brown, L. Baker, and F. Drobniewski
Can 15-Locus Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeat Analysis Provide Insight into the Evolution of Mycobacterium tuberculosis?
Appl. Envir. Microbiol., December 1, 2005; 71(12): 8207 - 8213.
[Abstract] [Full Text] [PDF]

Home page
 J Med MicrobiolHome page
C. Sholto-Douglas-Vernon, J. Sandy, T. C Victor, E. Sim, and P. D. Helden
Mutational and expression analysis of tbnat and its response to isoniazid
J. Med. Microbiol., December 1, 2005; 54(12): 1189 - 1197.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
K. Kremer, C. Arnold, A. Cataldi, M. C. Gutierrez, W. H. Haas, S. Panaiotov, R. A. Skuce, P. Supply, A. G. M. van der Zanden, and D. van Soolingen
Discriminatory Power and Reproducibility of Novel DNA Typing Methods for Mycobacterium tuberculosis Complex Strains
J. Clin. Microbiol., November 1, 2005; 43(11): 5628 - 5638.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
K. Svensson, P. Larsson, D. Johansson, M. Bystrom, M. Forsman, and A. Johansson
Evolution of Subspecies of Francisella tularensis
J. Bacteriol., June 1, 2005; 187(11): 3903 - 3908.
[Abstract] [Full Text] [PDF]

Home page
 J Med MicrobiolHome page
J. W Dale, G. H Bothamley, F. Drobniewski, S. H Gillespie, T. D McHugh, and R. Pitman
Origins and properties of Mycobacterium tuberculosis isolates in London
J. Med. Microbiol., June 1, 2005; 54(6): 575 - 582.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
N. Kurepina, E. Likhoshvay, E. Shashkina, B. Mathema, K. Kremer, D. van Soolingen, P. Bifani, and B. N. Kreiswirth
Targeted Hybridization of IS6110 Fingerprints Identifies the W-Beijing Mycobacterium tuberculosis Strains among Clinical Isolates
J. Clin. Microbiol., May 1, 2005; 43(5): 2148 - 2154.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
J. Song, Y. Xu, S. White, K. W. P. Miller, and M. Wolinsky
SNPsFinder--a web-based application for genome-wide discovery of single nucleotide polymorphisms in microbial genomes
Bioinformatics, May 1, 2005; 21(9): 2083 - 2084.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Achtman, G. Morelli, P. Zhu, T. Wirth, I. Diehl, B. Kusecek, A. J. Vogler, D. M. Wagner, C. J. Allender, W. R. Easterday, et al.
Microevolution and history of the plague bacillus, Yersinia pestis
PNAS, December 21, 2004; 101(51): 17837 - 17842.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
R. M. Warren, T. C. Victor, E. M. Streicher, M. Richardson, G. D. van der Spuy, R. Johnson, V. N. Chihota, C. Locht, P. Supply, and P. D. van Helden
Clonal Expansion of a Globally Disseminated Lineage of Mycobacterium tuberculosis with Low IS6110 Copy Numbers
J. Clin. Microbiol., December 1, 2004; 42(12): 5774 - 5782.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
K. Brudey, M. C. Gutierrez, V. Vincent, L. M. Parsons, M. Salfinger, N. Rastogi, and C. Sola
Mycobacterium africanum Genotyping Using Novel Spacer Oligonucleotides in the Direct Repeat Locus
J. Clin. Microbiol., November 1, 2004; 42(11): 5053 - 5057.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. Pearson, J. D. Busch, J. Ravel, T. D. Read, S. D. Rhoton, J. M. U'Ren, T. S. Simonson, S. M. Kachur, R. R. Leadem, M. L. Cardon, et al.
Phylogenetic discovery bias in Bacillus anthracis using single-nucleotide polymorphisms from whole-genome sequencing
PNAS, September 14, 2004; 101(37): 13536 - 13541.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. B. Beres, G. L. Sylva, D. E. Sturdevant, C. N. Granville, M. Liu, S. M. Ricklefs, A. R. Whitney, L. D. Parkins, N. P. Hoe, G. J. Adams, et al.
Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections
PNAS, August 10, 2004; 101(32): 11833 - 11838.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. G. Tsolaki, A. E. Hirsh, K. DeRiemer, J. A. Enciso, M. Z. Wong, M. Hannan, Y.-O. L. G. de la Salmoniere, K. Aman, M. Kato-Maeda, and P. M. Small
From the Cover: Functional and evolutionary genomics of Mycobacterium tuberculosis: Insights from genomic deletions in 100 strains
PNAS, April 6, 2004; 101(14): 4865 - 4870.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. E. Hirsh, A. G. Tsolaki, K. DeRiemer, M. W. Feldman, and P. M. Small
From the Cover: Stable association between strains of Mycobacterium tuberculosis and their human host populations
PNAS, April 6, 2004; 101(14): 4871 - 4876.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
M. H. Hazbon and D. Alland
Hairpin Primers for Simplified Single-Nucleotide Polymorphism Analysis of Mycobacterium tuberculosis and Other Organisms
J. Clin. Microbiol., March 1, 2004; 42(3): 1236 - 1242.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
T. C. Victor, P. E. W. de Haas, A. M. Jordaan, G. D. van der Spuy, M. Richardson, D. van Soolingen, P. D. van Helden, and R. Warren
Molecular Characteristics and Global Spread of Mycobacterium tuberculosis with a Western Cape F11 Genotype
J. Clin. Microbiol., February 1, 2004; 42(2): 769 - 772.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
M. Marmiesse, P. Brodin, C. Buchrieser, C. Gutierrez, N. Simoes, V. Vincent, P. Glaser, S. T. Cole, and R. Brosch
Macro-array and bioinformatic analyses reveal mycobacterial 'core' genes, variation in the ESAT-6 gene family and new phylogenetic markers for the Mycobacterium tuberculosis complex
Microbiology, February 1, 2004; 150(2): 483 - 496.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
N. H. Smith, J. Dale, J. Inwald, S. Palmer, S. V. Gordon, R. G. Hewinson, and J. M. Smith
The population structure of Mycobacterium bovis in Great Britain: Clonal expansion
PNAS, December 9, 2003; 100(25): 15271 - 15275.
[Abstract] [Full Text] [PDF]