Phylogenetic reconstruction within Mycobacterium tuberculosis Beijing genotype in northwestern Russia

A selection of genetic markers was used to study the evolution of Mycobacterium tuberculosis Beijing family strains in northwestern Russia. A total of 221 of 434 epidemiologically unlinked isolates studied in 1996-2001 belonged to the Beijing family as determined by standard spoligotyping (signals 35-43). Ninety-six percent of these Beijing isolates ("typical") were closely related in IS6110-RFLP (D > 0.85) while 9 remaining isolates (2 different profiles, "atypical") were more distant from the rest (D = 0.6-0.7). Further analysis was performed on a selection of 12 typical and both atypical Beijing strains with different IS6110-RFLP profiles (2 isolates each). All 28 Beijing isolates studied had the KatG 463Leu allele, an intact mtp40 fragment of the mpcA gene, and an identical structure of the DR locus (15 DVRs) with an upstream IS6110 copy in opposite orientation. The IS6110-RFLP based neighbor-joining (distance) and quartet-puzzling (maximum-likelihood) trees showed that the branch lengths were considerably longer for atypical Beijing strains. Typical Beijing strains had the 1.02 kb Rv3135 PPE-family gene and two IS1547 copies (iplA and iplB) one of them (iplB) disrupted by IS6110 insertion. Atypical Beijing strains had the 1.97 kb Rv3135 gene and a single intact IS1547/iplA copy. We suggest that the M. tuberculosis Beijing family strains currently circulating in the northwest of Russia are relatively ancient and thus appear to be endemic in this region since evolutionarily distant time. The prevalent typical Beijing strains (96%) are likely to be of monophyletic origin and their ongoing dissemination has started recently: these strains differ in rapidly evolving IS6110-RFLP but have identical structure of other polymorphic genome regions studied. The atypical Beijing strains (4%) are evolutionary older; they probably had a common (unknown) ancestor with typical Beijing strains.