We analyzed a global collection of Mycobacterium tuberculosis strains using 212 single nucleotide polymorphism (SNP) markers. SNP nucleotide diversity was high (average across all SNPs, 0.19), and 96% of the SNP locus pairs were in complete linkage disequilibrium. Cluster analyses identified six deeply branching, phylogenetically distinct SNP cluster groups (SCGs) and five subgroups. The SCGs were strongly associated with the geographical origin of the M. tuberculosis samples and the birthplace of the human hosts. The most ancestral cluster (SCG-1) predominated in patients from the Indian subcontinent, while SCG-1 and another ancestral cluster (SCG-2) predominated in patients from East Asia, suggesting that M. tuberculosis first arose in the Indian subcontinent and spread worldwide through East Asia. Restricted SCG diversity and the prevalence of less ancestral SCGs in indigenous populations in Uganda and Mexico suggested a more recent introduction of M. tuberculosis into these regions. The East African Indian and Beijing spoligotypes were concordant with SCG-1 and SCG-2, respectively; X and Central Asian spoligotypes were also associated with one SCG or subgroup combination. Other clades had less consistent associations with SCGs. Mycobacterial interspersed repetitive unit (MIRU) analysis provided less robust phylogenetic information, and only 6 of the 12 MIRU microsatellite loci were highly differentiated between SCGs as measured by G(ST). Finally, an algorithm was devised to identify two minimal sets of either 45 or 6 SNPs that could be used in future investigations to enable global collaborations for studies on evolution, strain differentiation, and biological differences of M. tuberculosis.
C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Div Infect Dis, 185 S Orange Ave, Newark, NJ 07103 USA.
Univ Med & Dent New Jersey, New Jersey Med Sch, Ruy V Lourence Ctr Study Emerging & Reemerging Pa, Newark, NJ 07103 USA.
Michigan State Univ, Toxicol Ctr, E Lansing, MI 48824 USA.
Inst Genom Res, Rockville, MD USA.
Univ Arkansas Med Sci, CAVHS, Dept Pathol, Little Rock, AR 72205 USA.
Univ Arkansas Med Sci, CAVHS, Dept Immunol Microbiol, Little Rock, AR 72205 USA.
Univ Arkansas Med Sci, CAVHS, Dept Neurobiol, Little Rock, AR 72205 USA.
Univ Arkansas Med Sci, CAVHS, Dept Dev Sci, Little Rock, AR 72205 USA.
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Infect Dis, Mexico City, DF, Mexico.
Inst Nacl Salud Publ, Unidad TB, Mexico City, DF, Mexico.
Univ Autonoma Nuevo Leon, Univ Hosp Monterrey, Pulm Serv, Nuevo Leon, Mexico.
Victorian Infect Dis Reference Lab, Victorian Mycobacterium Reference Lab, Melbourne, Vic 3051, Australia.
Inst Pasteur Guadeloupe, Unite TB & Mycobacteries, F-97183 Abymes, Guadeloupe, France.
Inst Nacl Salud, Grp Micobacterias, Subdirecc Invest, Bogota, Colombia.
Inonu Univ, Fac Med, Dept Clin Microbiol, Malatya, Turkey.
Makerere Univ, Dept Med, Kampala, Uganda.
Makerere Univ, Dept Med Microbiol, Kampala, Uganda.