Single-nucleotide polymorphism-based population genetic analysis of Mycobacterium tuberculosis strains from 4 geographic sites.
We studied genetic relationships among 5069 Mycobacterium tuberculosis strains recovered from patients enrolled in 4 population-based studies in the United States and Europe, by analysis of 36 synonymous single-nucleotide polymorphisms (SNPs). All strains were assigned to 1 of 9 major genetic clusters based on sSNP profile. The same 9 genetic clusters were revealed by analysis of 227 nonsynonymous SNPs, 121 intergenic SNPs, and concatenated profiles of 578 SNPs available for a subset of 48 representative strains. IS6110 profiles, spoligotypes, and mycobacterial interspersed repetitive unit patterns were nonrandomly associated with SNP-based phylogenetic lineages, together indicating a strongly clonal population structure. Isolates of the 9 genetic clusters were not distributed with equal frequency in all localities, reflecting geographic subdivision. The SNP-based phylogenetic framework provides new insight into the worldwide evolution of M. tuberculosis and a gateway for investigating genotype-disease phenotype relationships in large samples of strains.
Gutacker
Michaela M
MM
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Mathema
Barun
B
Soini
Hanna
H
Shashkina
Elena
E
Kreiswirth
Barry N
BN
Graviss
Edward A
EA
Musser
James M
JM
D015373:Bacterial Typing Techniques; D004251:DNA Transposable Elements; D005060:Europe / Q000453:epidemiology; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics*; D009841:Oligonucleotides / Q000032:analysis; D010802:Phylogeny; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology* / Q000382:microbiology; D014481:United States / Q000453:epidemiology
D004251:DNA Transposable Elements; D009841:Oligonucleotides