Genomic insights into the CRISPR-Cas system of Mycobacterium tuberculosis complex and its evolution
Anoop Singh1, Mohita Gaur1, Vishal Sharma1, Palak Khanna1, Ankur Bothra2, Asani Bhaduri3, Anupam Kumar Mondal2, Debasis Dash2, Yogendra Singh1, Richa Misra1,4
1Department of Zoology, University of Delhi, Delhi, India; 2CSIR-IGIB, Sukhdev Vihar, Mathura Road, New Delhi, India; 3Cluster Innovation Centre, University of Delhi, Delhi, India; 4Department of Zoology, Sri Venkateswara College, University of Delhi, Delhi, India
Mycobacterium tuberculosis, the causative agent of tuberculosis (TB) disease, infects around one-third of the world population latently and remains the major cause of infectious disease-related deaths worldwide. Although the clustered regularly interspaced short palindromic repeats (CRISPR) locus has been utilized for the genotyping of Mycobacterium tuberculosis complex (MTBC) strains useful in clinical diagnostics, its evolutionary origin and divergence are not well studied. In this study, we have performed a comparative genomic analysis of 135 mycobacterial species. We identified the exclusive presence of the CRISPR-Cas type III-A system in the MTBC. Our study highlights the evidence of inter-phyla horizontal gene transfer of the CRISPR-Cas locus in the last common ancestor of MTBC members from an environmental bacterium. Additionally, our results showed the IS6110 transposition derived variations and partial deletion of CRISPR-Cas locus in some M. tuberculosis lineages, especially the Beijing lineage. Such genomic comparisons of M. tuberculosis lineages with related bacteria offer valuable insights into the evolutionary history and emergence of pathogenic strains which in turn can help in controlling the global TB epidemic and future spillover events by the development of new diagnostic techniques and treatment.