Genetic Recombination of the rpoB Gene as a Mechanism of the Mycobacterium tuberculosis Resistance to Rifampin

The molecular genetic mechanisms whereby Mycobacterim tuberculosis develops resistance to rifampin (RIF) are poorly understood.？ Using the tests for selection and genetic recombination, we analyzed rpoB loci of the M. tuberculosis strains harboring the synonymous single nucleotide polymorphisms (sSNPs) to detect the horizontal gene transfer (HGT) of this genetic locus.？ The rpoB codons GGC507, GGG534, GGC556 and GGG566 were revealed to be the hotspots for the multiple sSNPs.？ The strains carrying multiple nucleotide polymorphisms across these codons were from either Iran or the Republic of Belarus, exhibiting regional patterns of the rpoB sSNPs distribution.？ The dN/dS ratios were ≤0.7363 for the rpoB loci that harbored these sSNPs, showing no significant selective pressures on the amino acid changes. The Index of Association (IA) being 1.110, for the DNA substitutions of the rpoB loci with the sSNPs, revealed that this genetic locus is not clonal in M. tuberculosis. Moreover, the splitstree analysis resulted in the parallelograms with the strong fit and bootstrap values (95-100 and 85-100 respectively), exhibiting the HGT events in some of these rpoB loci.？ Thus, it is strongly suggested that the HGT of rpoB of M. tuberculosis contributes to the generation of this species resistance to RIF.