Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis
- Timothy P. Stinear1,10,
- Torsten Seemann2,
- Paul F. Harrison2,
- Grant A. Jenkin1,
- John K. Davies1,
- Paul D.R. Johnson3,
- Zahra Abdellah4,
- Claire Arrowsmith4,
- Tracey Chillingworth4,
- Carol Churcher4,
- Kay Clarke4,
- Ann Cronin4,
- Paul Davis4,
- Ian Goodhead4,
- Nancy Holroyd4,
- Kay Jagels4,
- Angela Lord4,
- Sharon Moule4,
- Karen Mungall4,
- Halina Norbertczak4,
- Michael A. Quail4,
- Ester Rabbinowitsch4,
- Danielle Walker4,
- Brian White4,
- Sally Whitehead4,
- Pamela L.C. Small5,
- Roland Brosch6,
- Lalita Ramakrishnan7,
- Michael A. Fischbach8,
- Julian Parkhill4, and
- Stewart T. Cole9
- 1 Department of Microbiology, Monash University, Clayton 3800, Australia;
- 2 Victorian Bioinformatics Consortium, Monash University, Clayton 3800, Australia;
- 3 Department of Infectious Diseases, Austin Hospital, Heidelberg 3084, Australia;
- 4 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom;
- 5 Department of Microbiology, University of Tennessee, M409 Walters Life Sciences, Knoxville, Tennessee 37996-0845, USA;
- 6 Institut Pasteur, UP Pathogénomique Mycobactérienne Intégrée, 75015 Paris, France;
- 7 Department of Microbiology, University of Washington, Seattle, Washington 98195, USA;
- 8 Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA;
- 9 Global Health Institute, EPFL, Station 15, CH-1015, Lausanne, Switzerland
Abstract
Mycobacterium marinum, a ubiquitous pathogen of fish and amphibia, is a near relative of Mycobacterium tuberculosis, the etiologic agent of tuberculosis in humans. The genome of the M strain of M. marinum comprises a 6,636,827-bp circular chromosome with 5424 CDS, 10 prophages, and a 23-kb mercury-resistance plasmid. Prominent features are the very large number of genes (57) encoding polyketide synthases (PKSs) and nonribosomal peptide synthases (NRPSs) and the most extensive repertoire yet reported of the mycobacteria-restricted PE and PPE proteins, and related-ESX secretion systems. Some of the NRPS genes comprise a novel family and seem to have been acquired horizontally. M. marinum is used widely as a model organism to study M. tuberculosis pathogenesis, and genome comparisons confirmed the close genetic relationship between these two species, as they share 3000 orthologs with an average amino acid identity of 85%. Comparisons with the more distantly related Mycobacterium avium subspecies paratuberculosis and Mycobacterium smegmatis reveal how an ancestral generalist mycobacterium evolved into M. tuberculosis and M. marinum. M. tuberculosis has undergone genome downsizing and extensive lateral gene transfer to become a specialized pathogen of humans and other primates without retaining an environmental niche. M. marinum has maintained a large genome so as to retain the capacity for environmental survival while becoming a broad host range pathogen that produces disease strikingly similar to M. tuberculosis. The work described herein provides a foundation for using M. marinum to better understand the determinants of pathogenesis of tuberculosis.
Footnotes
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↵10 Corresponding author.
↵10 E-mail tim.stinear{at}med.monash.edu.au; fax 61-3-9905-4811.
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[Supplemental material is available online at www.genome.org. The sequence data from this study have been submitted to GenBank under accession nos. CP000854 (chromosome) and CP000895 (pMM23 plasmid).]
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Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.075069.107.
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- Received November 30, 2007.
- Accepted February 24, 2008.
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Freely available online through the Genome Research Open Access option.
- Copyright © 2008, Cold Spring Harbor Laboratory Press
