Evolutionary clues from comparative analysis of Mycobacterium tuberculosis variable-number tandem repeat sequences within genetic families

Mycobacterium tuberculosis is one of the most successful bacterial pathogens in the history of mankind, and the study of the evolutionary and genetic behaviour of this organism is ongoing. The potential of variable-number tandem repeat (VNTR) regions to provide insight into the evolutionary past of this organism has yet to be evaluated. The aim of this study was to investigate diversity occurring within VNTR loci within established evolutionary lineages. Mycobacterial interspersed repetitive unit (MIRU) 4 and 26 nucleotide sequencing was undertaken revealing significant differences in VNTR discriminatory power and distribution of allelic types within defined sub-lineages, within a moderately discriminant and a highly discriminant locus, respectively. These findings indicate potential allele bias at these loci within the defined groups dependent on the genotype of their progenitor strain, and the patterns of distribution suggest that a step-wise contraction/expansion process is responsible for VNTR repeat evolution. The results also identified a possible incidence of genetic drift within major genetic group 2 (MGG2), which has a point mutation at locus MIRU26 in a clonal subgroup.