Evidence for Recombination inMycobacterium tuberculosis

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Abstract
Due to its mostly isolated living environment, Mycobacterium tuberculosis is generally believed to be highly clonal, and thus recombination between different strains must be rare and is not critical for the survival of the species. To investigate the roles recombination could have possibly played in the evolution of M. tuberculosis, an analysis was conducted on previously determined genotypes of 36 synonymous single nucleotide polymorphisms (SNPs) in 3,320 M. tuberculosis isolates. The results confirmed the predominant clonal structure of the M. tuberculosis population. However, recombination between different strains was also suggested. To further resolve the issue, 175 intergenic SNPs and 234 synonymous SNPs were genotyped in 37 selected representative strains. A clear mosaic polymorphic pattern ahead of the MT0105 locus encoding a PPE (Pro-Pro-Glu) protein was obtained, which is most likely a result of recombination hot spot. Given that PPE proteins are thought to be critical in host-pathogen interactions, we hypothesize that recombination has been influential in the history of M. tuberculosis and possibly a major contributor to the diversity observed ahead of the MT0105 locus.