Purifying Selective Pressure Suggests the Functionality of a Vitamin B12 Biosynthesis Pathway in a Global Population of Mycobacterium tuberculosis

Mycobacterium tuberculosis is one of the deadliest and most challenging pathogens to study in current microbiological research. One of the issues that remains to be resolved is the importance of cobalamin in the metabolism of M. tuberculosis. The functionality of a vitamin B12 biosynthesis pathway in M. tuberculosis is under dispute, and the ability of this pathogen to scavenge vitamin B12 from the host is unknown. Here, we quantified the ratios of nonsynonymous and synonymous nucleotide substitution rates (dN/dS) in the genes involved in vitamin B12 biosynthesis and transport and in genes encoding cobalamin-dependent enzymes in nearly four thousand strains of M. tuberculosis. We showed that purifying selection is the dominant force acting on cobalamin-related genes at the levels of individual codons, genes and groups of genes. We conclude that cobalamin-related genes may not be essential but are adaptive for M. tuberculosis in clinical settings. Furthermore, the cobalamin biosynthesis pathway is likely to be functional in this species.