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Massive gene decay in the leprosy bacillus

Abstract

Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.

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Figure 1: Circular genome map showing the position and orientation of known genes, pseudogenes and repetitive sequences.
Figure 2: Comparison of the proS loci of M. leprae and M. tuberculosis.
Figure 3: Distribution of genes by functional category.

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Acknowledgements

We are grateful to B. R. Bloom, P. J. Brennan, M. J. Colston, J. Grosset and B. Ji for advice, reagents and encouragement. This work was supported by the New York Community Trust, ILEP, the Association Française Raoul Follereau, the Wellcome Trust and the Institut Pasteur.

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Cole, S., Eiglmeier, K., Parkhill, J. et al. Massive gene decay in the leprosy bacillus. Nature 409, 1007–1011 (2001). https://doi.org/10.1038/35059006

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