Abstract
Comparison of genome sequences from clinical isolates of Mycobacterium tuberculosis with phylogenetically-related pathogens Mycobacterium marinum, Mycobacterium kansasii, and Mycobacterium leprae reveals diversity amongst genes associated with vitamin B12-related metabolism. Diversity is generated by gene deletion events, differential acquisition of genes by horizontal transfer, and single nucleotide polymorphisms (SNPs) with predicted impact on protein function and transcriptional regulation. Differences in the B12 synthesis pathway, methionine biosynthesis, fatty acid catabolism, and DNA repair and replication are consistent with adaptations to different environmental niches and pathogenic lifestyles. While there is no evidence of further gene acquisition during expansion of the M. tuberculosis complex, the emergence of other forms of genetic diversity provides insights into continuing host-pathogen co-evolution and has the potential to identify novel targets for disease intervention.
Highlights
Strains belonging to the Mycobacterium tuberculosis complex evolved by clonal expansion from a common ancestral population shared with Mycobacterium canettii, an occasional human pathogen closely resembling M. tuberculosis in terms of disease and evolution
NrdZ is differentially distributed amongst the mycobacteria in a pattern that is inconsistent with conventional phylogeny (Figure 9A); while it is present in slow-growing M. tuberculosis and M. kansasii and rapid-growing M. phlei, for example, it is absent from M. marinum and M. smegmatis
PncA is inactivated by an H57D single nucleotide polymorphisms (SNPs) in cattle-adapted M. bovis, an L177R SNP is predicted to impact PncB2 function in Lineage 5, and PncA mutations are selected in pyrazinamide-resistant strains of M. tuberculosis without incurring any loss in pathogenesis, suggesting that retention of de novo synthesis is preferred over host scavenging as a source of the vitamin
Summary
Strains belonging to the Mycobacterium tuberculosis complex evolved by clonal expansion from a common ancestral population shared with Mycobacterium canettii, an occasional human pathogen closely resembling M. tuberculosis in terms of disease and evolution. In the case of CobN/Rv2026c, screening a panel of more than 200 clinical isolates representative of the global diversity of M. tuberculosis (Comas et al, 2013) identifies 17 SNPs predicted to have an impact on protein function, two strains with >1 kb deletion, and truncated proteins generated by frameshift events.
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