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Massive gene decay in the leprosy bacillus.
Open accessAbstract
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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“Apart from members of the M. tuberculosis complex, the ESX-1 cluster is also present in a range of mycobacteria, including Mycobacterium kansasii [23] and Mycobacterium leprae [42].”
From Systematic Genetic Nomenclature for Type VII Secretion Systems (2009) · cites this paper as [42]
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“Furthermore, in M. leprae, an organism with an extreme reductive evolution of its genome, almost all of the non-conserved ESX-1 components are pseudogenes, whereas all of the conserved components seem to be intact [42].”
From Systematic Genetic Nomenclature for Type VII Secretion Systems (2009) · cites this paper as [42]
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Self-citation
Metadata
- Authors
- Cole, S. T., Eiglmeier, K., Parkhill, J., James, K. D., Thomson, N. R., Wheeler, P. R., Honoré, N., Garnier, T., Churcher, C., Harris, D., Mungall, K., Basham, D., Brown, D., Chillingworth, T., Connor, R., Davies, R. M., Devlin, K., Duthoy, S., Feltwell, T., Fraser, A., Hamlin, N., Holroyd, S., Hornsby, T., Jagels, K., Lacroix, C., Maclean, J., Moule, S., Murphy, L., Oliver, K., Quail, M. A., Rajandream, M.-A., Rutherford, K. M., Rutter, S., Seeger, K., Simon, S., Simmonds, M., Skelton, J., Squares, R., Squares, S., Stevens, K., Taylor, K., Whitehead, S., Woodward, J. R., & Barrell, B. G.
- Affiliations
- Institut Pasteur (FR)
- Wellcome Sanger Institute (GB)
- Animal and Plant Health Agency (GB)
- Corresponding author
- Cole, S. T.
- ORCID
- Venue
- Nature
- Published
- 2001-02
- Volume
- 409
- Issue
- 6823
- Pages
- 1007-1011
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2164217177
- Cited by
- 1,777
- References
- 50
- Citations by year
- 2026: 22 · 2025: 32 · 2024: 34 · 2023: 30 · 2022: 38 · 2021: 41 · 2020: 49 · 2019: 50 · 2018: 51 · 2017: 55 · 2016: 64 · 2015: 75 · 2014: 80 · 2013: 63 · 2012: 79
- FWCI
- 94.38
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- New York Community Trust
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Infectious Diseases › Leprosy Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
- Keywords
- Mycobacterium leprae, leprosy, genome reduction, reductive evolution, pseudogenes, gene decay, Mycobacterium tuberculosis, recombination, gene deletion, siderophore production, electron transport chain
- MeSH terms
- Animals, Armadillos, DNA, Bacterial, Energy Metabolism, Multigene Family, Humans, Leprosy, Molecular Sequence Data, Mycobacterium leprae, Genome, Bacterial, Sequence Analysis, DNA, Evolution, Molecular, Gene Transfer, Horizontal
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