Before the genomic era there was already a longstanding interest in understanding the origins of bacterial pathogens and the molecular attributes of virulence. Large-scale genome sequencing has provided a rapid and unbiased means of uncovering the evolution of many pathogens, contributing to both fundamental microbiological insights and the development of new disease-control strategies. For these reasons, the evolution of one of the most devastating human pathogens, Mycobacterium tuberculosis, has captivated researchers since its discovery in 1882. This interest was stimulated not only by the epidemiologic importance of the pathogen but also by the lack of consensus on its origins and its apparent exception to the stereotypes of bacterial evolution (e.g. acquisition of pathogenicity islands). So where did M. tuberculosis come from?
The rise and fall of the Mycobacterium tuberculosis genome. Trends Microbiol. 2011 19(4): 156-161
When studied from the perspective of non-tuberculous mycobacteria (NTM) it is apparent that Mycobacterium tuberculosis has undergone a biphasic evolutionary process involving genome expansion (gene acquisition and duplication) and reductive evolution (deletions). This scheme can instruct descriptive and experimental studies that determine the importance of ancestral events (including horizontal gene transfer) in shaping the present-day pathogen. For example, heterologous complementation in an NTM can test the functional importance of M. tuberculosis-specific genetic insertions. An appreciation of both phases of M. tuberculosis evolution is expected to improve our fundamental understanding of its pathogenicity and facilitate the evaluation of novel diagnostics and vaccines.