An ancestral genomic locus in Mycobacterium tuberculosis clinical isolates from India hints the genetic link with Mycobacterium canettii.

Abstract

Tuberculosis remains a worldwide public health emergency. To better understand M. tuberculosis and to identify genomic variations characteristic to the Indian clinical isolates by a low-cost method, a genomic subtractive hybridization between M. tuberculosis H37Rv and a clinical isolate from South India was performed. This revealed a novel 0.4-kb subtractive fragment which was used as a handle to pull out a 4.5-kb genomic region characteristic to the clinical isolate and was absent in H37Rv. On further studies, this 4.5-kb region was found to be present in 91% of the M. tuberculosis clinical isolates screened from Kerala, a state in South India. Interestingly, this novel region has 99% identity (with 100% query coverage) with genomic regions of M. canettii. The present study hypothesizes that this locus was present in the recent common environmental ancestor of mycobacteria, retained to the maximum extent in M. canettii and ancestral isolates of M. tuberculosis, and later deleted in other modern lineages of M. tuberculosis. Thus, this region may serve as one of the links between the pathogenic mycobacteria and the environmental species. We also propose that the Indian isolates of M. tuberculosis might be closely related to the putative progenitor M. prototuberculosis with respect to this locus. More studies on other genomic loci from different strains of M. tuberculosis are required to establish more links in this direction.