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Abstract

Full genome comparisons of Mycobacterium: Insight into the origin of tuberculosis and leprosy

Abstract

Resolving the origins and antiquity of the two major mycobacterial diseases, tuberculosis and leprosy, provides a framework for the study of the co-evolution of humans and the ancient obligate pathogens Mycobacterium tuberculosis and Mycobacterium leprae. Elucidating the relationships of pathogenic and nonpathogenic mycobacteria has been limited due to the lack of resolution obtained with single- or multi-locus analyses. The purpose of this study is to determine robust phylogenetic relationships and divergence times within the pathogenic mycobacteria and the genus as a whole using a genomescale analysis.

Complete genomes of nine species/strains of pathogenic and nonpathogenic mycobacteria were obtained from Genbank and the Sanger Institute, along with their predicted protein sequences. We then identified 497 protein coding genes (~540,000 base pairs) shared by all nine genomes. Phylogenetic analyses of these data using three different methods yielded identical topologies with 100% bootstrap values for all branches. M. leprae is situated basal to the M. tuberculosis complex (MTBC), in contrast with previous studies. Pairwise genome divergence times were obtained using the number of synonymous substitutions per site and applying the mutation rate of enterobacteria. Our results indicate that M. leprae and the MTBC diverged some 36 million years ago, a much deeper timescale for the origins of these pathogens than previously presumed, which suggests a coevolutionary history that begins around the time of anthropoid-prosimian divergence. Further, members of the MTBC included in this study diverged approximately 115 thousand years ago and this expansion corresponds in time with modern human evolution.

Full Citation

Pfister, L.-A., M.S. Rosenberg, and A.C. Stone (2008) Full genome comparisons of Mycobacterium: Insight into the origin of tuberculosis and leprosy. American Journal of Physical Anthropology 135(S46):171.

DOI

10.1002/ajpa.20806

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