The DOI matches its Crossref record; 49 of the 50 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
In the citing paper
“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]
Citations
Cites
Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence
Cole, S. T., Brosch, R., Parkhill, J., Garnier, T., Churcher, C., Harris, D., Gordon, S. V., Eiglmeier, K., Gas, S., Barry, C. E., et al. (1998) · Nature · doi:10.1038/31159 · Cited by 7,847
Self-citationArtemis: sequence visualization and annotation
Rutherford, K. M., Parkhill, J., Crook, J., Horsnell, T., Rice, P., Rajandream, M., & Barrell, B. (2000) · Bioinform. · doi:10.1093/bioinformatics/16.10.944 · Cited by 3,295
Self-citationThe genome sequence of Rickettsia prowazekii and the origin of mitochondria
Andersson, S. G. E., Zomorodipour, A., Andersson, J. O., Sicheritz-Pontén, T., Alsmark, U. C. M., Podowski, R. M., Näslund, A. K., Eriksson, A.-S., Winkler, H. H., & Kurland, C. G. (1998) · Nature · doi:10.1038/24094 · Cited by 1,697
McKinney, J. D., zu Bentrup, K. H., Muñoz‐Elías, E. J., Miczák, A., Chen, B., Chan, W.-T., Swenson, D. L., Sacchettini, J. C., Jacobs, W. R., & Russell, D. G. (2000) · Nature · doi:10.1038/35021074 · Cited by 1,361
A new DNA sequence assembly program
Bonfield, J., Smith, K. F., & Staden, R. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.24.4992 · Cited by 978
Issues in searching molecular sequence databases
Altschul, S. F., Boguski, M. S., Gish, W. R., & Wootton, J. C. (1994) · Nature Genetics · doi:10.1038/ng0294-119 · Cited by 773
Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice
Cox, J. S., Chen, B., McNeil, M., & Jacobs, W. R. (1999) · Nature · doi:10.1038/47042 · Cited by 746
The Envelope Layers of Mycobacteria with Reference to their Pathogenicity
Daffé, M., & Draper, P. (1997) · Advances in microbial physiology/Advances in Microbial Physiology · doi:10.1016/s0065-2911(08)60016-8 · Cited by 727
Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491
Parkhill, J., Achtman, M., James, K., Bentley, S. D., Churcher, C. M., Klee, S. R., Morelli, G., Basham, D., Brown, D., Chillingworth, T., et al. (2000) · Nature · doi:10.1038/35006655 · Cited by 699
Self-citationGlickman, M. S., Cox, J. S., & Jacobs, W. R. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80250-6 · Cited by 656
Camacho, L. R., Ensergueix, D., Pérez‐Herrán, E., Gicquel, B., & Guilhot, C. (1999) · Molecular Microbiology · doi:10.1046/j.1365-2958.1999.01593.x · Cited by 616
De Voss, J. J., Rutter, K., Schroeder, B. G., Su, H., Zhu, Y., & Barry, C. E. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.3.1252 · Cited by 532
Molecular Genetics of Mycobacteria
(2014) · ASM Press eBooks · doi:10.1128/9781555818845 · Cited by 430
Ramakrishnan, L., Federspiel, N. A., & Falkow, S. (2000) · Science · doi:10.1126/science.288.5470.1436 · Cited by 420
Quadri, L. E. N., Sello, J. K., Keating, T. A., Weinreb, P. H., & Walsh, C. T. (1998) · Chemistry & Biology · doi:10.1016/s1074-5521(98)90291-5 · Cited by 418
Wolf, Y. I., Aravind, L., Grishin, N. V., & Koonin, E. V. (1999) · Genome Research · doi:10.1101/gr.9.8.689 · Cited by 410
Cloning of an M. tuberculosis DNA fragment associated with entry and survival inside cells
Arruda, S. M., Bomfim, G. F., Knights, R. W., Huima-Byron, T., & Riley, L. W. (1993) · Science · doi:10.1126/science.8367727 · Cited by 385
Jungblut, P. R., Schaible, U. E., Mollenkopf, H., Zimny‐Arndt, U., Raupach, B., Mattow, J., Halada, P., Lamer, S., Hagens, K., & Kaufmann, S. H. E. (1999) · Molecular Microbiology · doi:10.1046/j.1365-2958.1999.01549.x · Cited by 327
Analysis of the proteome of Mycobacterium tuberculosis in silico
Tekaia, F., Gordon, S. V., Garnier, T., Brosch, R., Barrell, B. G., & Cole, S. T. (1999) · Tubercle and Lung Disease · doi:10.1054/tuld.1999.0220 · Cited by 311
Self-citationzu Bentrup, K. H., Miczák, A., Swenson, D. L., & Russell, D. G. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.23.7161-7167.1999 · Cited by 278
The Biology of the Mycobacteria
Ratledge, C., & Stanford, J. A. (1982) · Cited by 248
Makui, H., Roig, E. A., Cole, S. T., Helmann, J. D., Gros, P., & Cellier, M. F. (2000) · Molecular Microbiology · doi:10.1046/j.1365-2958.2000.01774.x · Cited by 240
Self-citationInsights into the evolutionary process of genome degradation
Andersson, J. O., & Andersson, S. G. E. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)00024-6 · Cited by 236
Role of α-Dystroglycan as a Schwann Cell Receptor for Mycobacterium leprae
Rambukkana, A., Yamada, H., Zanazzi, G. J., Mathus, T., Salzer, J. L., Yurchenco, P. D., Campbell, K. P., & Fischetti, V. A. (1998) · Science · doi:10.1126/science.282.5396.2076 · Cited by 231
Kirchheimer, W. F., & Storrs, E. E. (1972) · PubMed · Cited by 205
Neural Targeting of Mycobacterium leprae Mediated by the G Domain of the Laminin-α2 Chain
Rambukkana, A., Salzer, J. L., Yurchenco, P. D., & TUOMANEN, E. I. (1997) · Cell · doi:10.1016/s0092-8674(00)81927-3 · Cited by 174
Ishiguro, T., Saitoh, J., Yawata, H., Otsuka, M., Inoue, T., & SUGIURA, Y. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.24.4992 · Cited by 173
Stinear, T. P., Jenkin, G., Johnson, P. D. R., & Davies, J. K. (2000) · Journal of Bacteriology · doi:10.1128/jb.182.22.6322-6330.2000 · Cited by 164
Shimoji, Y., Ng, V. H., Matsumura, K., Fischetti, V. A., & Rambukkana, A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.17.9857 · Cited by 141
A close family resemblance: the importance of structure in understanding cytochromes P450
Peterson, J. A., & Graham, S. E. (1998) · Structure · doi:10.1016/s0969-2126(98)00109-9 · Cited by 135
Yuan, Y., & Barry, C. E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.23.12828 · Cited by 132
Learning from the genome sequence of Mycobacterium tuberculosis H37Rv
Cole, S. T. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00536-0 · Cited by 128
Self-citationMapping and Identification of the Major Cell Wall-Associated Components of Mycobacterium leprae
Marques, M. A. M., Chitale, S., Brennan, P. J., & Pessolani, M. C. V. (1998) · Infection and Immunity · doi:10.1128/iai.66.6.2625-2631.1998 · Cited by 120
Gordon, S. V., Heym, B., Parkhill, J., Barrell, B. G., & Cole, S. T. (1999) · Microbiology · doi:10.1099/13500872-145-4-881 · Cited by 115
Self-citationUse of an ordered cosmid library to deduce the genomic organization of Mycobacterium leprae
Eiglmeier, K., Honoré, N., Woods, S. A., Caudron, B., & Cole, S. T. (1993) · Molecular Microbiology · doi:10.1111/j.1365-2958.1993.tb01111.x · Cited by 109
Self-citationMetabolism ofMycobacterium tuberculosis
Wheeler, P. R., & Ratledge, C. (2014) · ASM Press eBooks · doi:10.1128/9781555818357.ch23 · Cited by 99
Self-citationImmunological significance of Mycobacterium leprae cell walls.
Melancon-Kaplan, J., Hunter, S. W., McNeil, M., Stewart, C., Modlin, R. L., Rea, T. H., Convit, J., Salgame, P. R., Mehra, V. L., & Bloom, B. R. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.6.1917 · Cited by 66
Comparative genomics of the leprosy and tubercle bacilli
Brosch, R., Gordon, S. V., Eiglmeier, K., Garnier, T., & Cole, S. T. (2000) · Research in Microbiology · doi:10.1016/s0923-2508(00)00117-0 · Cited by 55
Self-citationDrug susceptibility testing of Mycobacterium leprae in the BACTEC 460 system
Franzblau, S. G. (1989) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.33.12.2115 · Cited by 49
Repeated DNA sequences in mycobacteria
Poulet, S., & Cole, S. T. (1995) · Archives of Microbiology · doi:10.1007/bf00381780 · Cited by 47
Self-citationMultiplex Sequencing of 1.5 Mb of the Mycobacterium leprae GenomePreprint
Smith, D. R., Richterich, P., Rubenfield, M., Rice, P. W., Butler, C., Lee, H.-M., Kirst, S., Gundersen, K., Abendschan, K., Xu, Q., et al. (1997) · Genome Research · doi:10.1101/gr.7.8.802 · Cited by 34
Self-citationDraper, P., Dobson, G., Minnikin, D. E., & MINNIKIN, S. M. (1982) · PubMed · Cited by 23
Wheeler, P. R. (1984) · Microbiology · doi:10.1099/00221287-130-2-381 · Cited by 17
Self-citationEiglmeier, K., Fsihi, H., Heym, B., & Cole, S. T. (1997) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1997.tb10340.x · Cited by 15
Self-citationMycobacterial genome structure (minireview)
Philipp, W. J., Schwartz, D. C., Telenti, A., & Cole, S. T. (1998) · Electrophoresis · doi:10.1002/elps.1150190418 · Cited by 12
Self-citationExochelin-mediated iron uptake into Mycobacterium leprae.
Rm, H., Pr, W., & Ratledge, C. (1983) · PubMed · Cited by 12
Cook, G. C. (1994) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(94)90128-7 · Cited by 4
Flagged first, then by citations
1 of the 50 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- World Health Organization in WHO Weekly Epidemiological Record 73, 40 (1998).
- Hansen, G. H. A. Undersogelser angaende spedalskhedens aasager. Norsk Magazin for Laegervidenskaben 4 (Suppl.), 1–88 (1874).
- Shephard, C. C. in Leprosy (ed. Hastings, R. C.) 269–286 (Churchill Livingstone, Edinburgh, 1985).
Cited by
Sorted by citations
Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2)
Bentley, S. D., Chater, K. F., Cerdeño-Tárraga, A. M., Challis, G. L., Thomson, N. R., James, K., Harris, D. E., Quail, M. A., Kieser, H. M., Harper, D., et al. (2002) · Nature · doi:10.1038/417141a · Cited by 3,226
Self-citationGenes required for mycobacterial growth defined by high density mutagenesis
Sassetti, C. M., Boyd, D. H., & Rubin, E. J. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03425.x · Cited by 2,544
ACT: the Artemis comparison tool
Carver, T. J., Rutherford, K., Berriman, M., Rajandream, M., BARRELL, B. G., & Parkhill, J. (2005) · Computer applications in the biosciences · doi:10.1093/bioinformatics/bti553 · Cited by 1,614
Self-citationExtreme genome reduction in symbiotic bacteria
McCutcheon, J. P., & Moran, N. A. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2670 · Cited by 1,464
Ikeda, H., Ishikawa, J., Hanamoto, A., SHINOSE, M., Kikuchi, H., Shiba, T., Sakaki, Y., Hattori, M., & Ōmura, S. (2003) · Nature Biotechnology · doi:10.1038/nbt820 · Cited by 1,238
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
