RT Journal A1 Stinear, Timothy P. A1 Seemann, Torsten A1 Harrison, Paul F. A1 Jenkin, Grant A. A1 Davies, John K. A1 Johnson, Paul D.R. A1 Abdellah, Zahra A1 Arrowsmith, Claire A1 Chillingworth, Tracey A1 Churcher, Carol A1 Clarke, Kay A1 Cronin, Ann A1 Davis, Paul A1 Goodhead, Ian A1 Holroyd, Nancy A1 Jagels, Kay A1 Lord, Angela A1 Moule, Sharon A1 Mungall, Karen A1 Norbertczak, Halina A1 Quail, Michael A. A1 Rabbinowitsch, Ester A1 Walker, Danielle A1 White, Brian A1 Whitehead, Sally A1 Small, Pamela L.C. A1 Brosch, Roland A1 Ramakrishnan, Lalita A1 Fischbach, Michael A. A1 Parkhill, Julian A1 Cole, Stewart T. T1 Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis JF Genome Research JO Genome Research YR 2008 FD May 01 VO 18 IS 5 SP 729 OP 741 DO 10.1101/gr.075069.107 UL http://genome.cshlp.org/content/18/5/729.abstract AB 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.