Population genetic analysis of Mycobacterium tuberculosis Beijing subgroup strains

Abstract

Population genetic analysis using variable-number tandem repeat (VNTR) data of 23 loci (15 “optimized MIRU” loci and eight “Beijing option” loci) was done on Mycobacterium tuberculosis Beijing lineage strains isolated in Japan. These strains were divided into Beijing subgroups (BSUB) B1–B5 and T2 by minimum spanning tree (MST) analysis. The ΦPT values among the BSUB, a measure of their molecular variance, were significantly different from zero with 999 permutations, indicating the validity of BSUB classification using the 23 VNTR loci. Higher number of migrants (Nm) values were observed between B1 and T2, B4 and T2, B3 and T2, and B3 and B4 in a phylogenetic network model reconstructed from previously reported single-nucleotide polymorphism (SNP) data. These BSUB combinations, except B3 and B4, shared SNP types; i.e., ST19 was in B1 and T2 and in B4 and T2, and STK was in B3 and T2. These results taken together suggested that shared SNP types were not due to homoplasy, but to strong genetic relatedness between those BSUB. Haploid genetic diversity and standardized index of association values were different in each BSUB, indicating that the diversity of each BSUB was different. Although the differences in BSUB diversity were mostly in accordance with the relative divergence order of the BSUB in a phylogenetic network model, the diversity of B4 was biased by a significant increase in the number of strains in this study from patients born after 1964 (Fisher’s exact test P<0.01). The different diversity of each BSUB indicated increased diversity of Beijing lineage strains, perhaps contributing to the survival and dissemination of these strains.