Phylogeny of Mycobacterium tuberculosis Beijing Strains Constructed from Polymorphisms in Genes Involved in DNA Replication, Recombination and Repair

Abstract

BackgroundThe Beijing family is a successful group of M. tuberculosis strains, often associated with drug resistance and widely distributed throughout the world. Polymorphic genetic markers have been used to type particular M. tuberculosis strains. We recently identified a group of polymorphic DNA repair replication and recombination (3R) genes. It was shown that evolution of M. tuberculosis complex strains can be studied using 3R SNPs and a high-resolution tool for strain discrimination was developed. Here we investigated the genetic diversity and propose a phylogeny for Beijing strains by analyzing polymorphisms in 3R genes.Methodology/Principal FindingsA group of 3R genes was sequenced in a collection of Beijing strains from different geographic origins. Sequence analysis and comparison with the ones of non-Beijing strains identified several SNPs. These SNPs were used to type a larger collection of Beijing strains and allowed identification of 26 different sequence types for which a phylogeny was constructed. Phylogenetic relationships established by sequence types were in agreement with evolutionary pathways suggested by other genetic markers, such as Large Sequence Polymorphisms (LSPs). A recent Beijing genotype (Bmyc10), which included 60% of strains from distinct parts of the world, appeared to be predominant.Conclusions/SignificanceWe found SNPs in 3R genes associated with the Beijing family, which enabled discrimination of different groups and the proposal of a phylogeny. The Beijing family can be divided into different groups characterized by particular genetic polymorphisms that may reflect pathogenic features. These SNPs are new, potential genetic markers that may contribute to better understand the success of the Beijing family.

Combination of Single Nucleotide Polymorphism and Variable-Number Tandem Repeats for Genotyping a Homogenous Population of Mycobacterium tuberculosis Beijing Strains in China

“…The 191 M. tuberculosis Beijing strains were divided into 8 sublineages by genotyping of the 8 SNPs (Table 1). Comparing these results with those of our previous study (31), one additional sublineage was characterized based on the mutation in adhE2 codon 124 (position 2532616 in the H37Rv genome). This new sublineage was named Bmyc210, as the corresponding mutation was first identified in strain 210 (14).…”

“…As a consequence, the discriminatory power of the standard 15-and 24-locus VNTR genotyping schemes was repeatedly demonstrated to be low for epidemiology studies in settings dominated by modern Beijing strains (18,25,35). Modern Beijing strains are also characterized by SNPs in the mutT2 and ogt genes, and their population structure has been further explored by using more recently evolved LSPs (RD142 and RD150) and SNPs (11,31,42). However, the frequencies of these polymorphisms vary in different settings (13,19,24,31).…”

“…Modern Beijing strains are also characterized by SNPs in the mutT2 and ogt genes, and their population structure has been further explored by using more recently evolved LSPs (RD142 and RD150) and SNPs (11,31,42). However, the frequencies of these polymorphisms vary in different settings (13,19,24,31).…”

“…For each gel, the corresponding VNTR allele of H37Rv was used for quality control. For SNP genotyping, eight SNPs in 3R genes were previously found in Beijing strains from Shanghai (31). Excluding the SNP in ogt codon 12, which is redundant with the SNP in mutT2 codon 58, the other seven SNPs were included for genotyping in this study.…”

Southern East Asian origin and coexpansion of Mycobacterium tuberculosis Beijing family with Han Chinese

“…With the increased availability of genotyping data, the Beijing strains were proved more heterogeneous than initially estimated, and several Beijing sublineages have been identified (28)(29)(30)(31). However, a full understanding of the genetic diversity of Beijing family is constrained by the low amount of nucleotide variation (8,32).…”