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 |
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| Authors: | Filliol Ingrid Motiwala Alifiya S Cavatore Magali Qi Weihong Hazbón Manzour Hernando Bobadilla del Valle Miriam Fyfe Janet García-García Lourdes Rastogi Nalin Sola Christophe Zozio Thierry Guerrero Marta Inírida León Clara Inés Crabtree Jonathan Angiuoli Sam Eisenach Kathleen D Durmaz Riza Joloba Moses L Rendón Adrian Sifuentes-Osornio José Ponce de León Alfredo Cave M Donald Fleischmann Robert Whittam Thomas S Alland David |
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| Affiliation: | Division of Infectious Disease, University of Medicine and Dentistry of New Jersey, 185 South Orange Ave., MSB A920C, Newark, NJ 07103. allandda@umdnj.edu. |
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| Abstract: | 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 GST. 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. |
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