SOME FEATURES OF GENOME STRUCTURE AND EVOLUTION OF MYCOBACTERIUM TUBERCULOSIS

Abstract

Abstract. Mycobacterium tuberculosis complex includes both human pathogens (M. tuberculosis, M. africanum and M. canettii), rodent paghogens (M. microti), as well as Mycobacterium bovis with wide range of hosts and related M. caprae and M. pinnipedii. In spite of phenotypic and host differences these species present a highly homogeneous genospecies with 99.7–99.9% of genome homology and extremely low level of horizontal gene transfer. Recent genetic research in the last decade permitted to revisit and revise old and new dogmas about genome and evolution of M. tuberculosis. In particular, a classical theory about bovine origin of human tuberculosis during domestication process was rejected. It was demonstrated that genomes of the related species of M. tuberculosis complex evolved through large unidirectional deletions leading to origin of M. tuberculosis sensu stricto, M. bovis and other species (M. canettii, M. microti, M. pinnipedii, M. caprae) from the same progenitor species. Large deletions influence the pathogenic potential of different clonal lineages within M. tuberculosis. At the same time, genetic variation within the short time frames is achieved via changes in the repetitive DNA and transposition of the insertion sequences IS6110 across the genome. Furthermore, M. tuberculosis may adapt to the selective pressure of the host immune system and antituberculosis drugs via specific point mutations. In the last few years a higher level of SNP variation between closely related strains was demonstrated with opens new perspectives for full-genome and multilocus sequence typing of M. tuberculosis.

Keywords

• molecular evolution
• mycobacterium tuberculosis
• genome
• is6110
• deletions
• polymorphism