6533b82bfe1ef96bd128d742

RESEARCH PRODUCT

Comparative Sequence Analysis ofMycobacterium lepraeand the New Leprosy-CausingMycobacterium lepromatosis

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ABSTRACTMycobacterium lepromatosisis a newly discovered leprosy-causing organism. Preliminary phylogenetic analysis of its 16S rRNA gene and a few other gene segments revealed significant divergence fromMycobacterium leprae, a well-known cause of leprosy, that justifies the status ofM. lepromatosisas a new species. In this study we analyzed the sequences of 20 genes and pseudogenes (22,814 nucleotides). Overall, the level of matching of these sequences withM. lepraesequences was 90.9%, which substantiated the species-level difference; the levels of matching for the 16S rRNA genes and 14 protein-encoding genes were 98.0% and 93.1%, respectively, but the level of matching for five pseudogenes was only 79.1%. Five conserved protein-encoding genes were selected to construct phylogenetic trees and to calculate the numbers of synonymous substitutions (dSvalues) and nonsynonymous substitutions (dNvalues) in the two species. Robust phylogenetic trees constructed using concatenated alignment of these genes placedM. lepromatosisandM. lepraein a tight cluster with long terminal branches, implying that the divergence occurred long ago. ThedSanddNvalues were also much higher than those for other closest pairs of mycobacteria. ThedSvalues were 14 to 28% of thedSvalues forM. lepraeandMycobacterium tuberculosis, a more divergent pair of species. These results thus indicate thatM. lepromatosisandM. lepraediverged ∼10 million years ago. TheM. lepromatosispseudogenes analyzed that were also pseudogenes inM. lepraeshowed nearly neutral evolution, and their relative ages were similar to those ofM. lepraepseudogenes, suggesting that they were pseudogenes before divergence. Taken together, the results described above indicate thatM. lepromatosisandM. lepraediverged from a common ancestor after the massive gene inactivation event described previously forM. leprae.