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Journal of Bacteriology, February 2009, p. 1018-1025, Vol. 191, No. 3
0021-9193/09/$08.00+0     doi:10.1128/JB.01340-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Insertion and Deletion Events That Define the Pathogen Mycobacterium avium subsp. paratuberculosis{triangledown} ,{ddagger}

David C. Alexander ,{dagger},§ Christine Y. Turenne,{dagger},§ and Marcel A. Behr*

McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada

Received 25 September 2008/ Accepted 17 November 2008

Mycobacterium avium comprises genetically related yet phenotypically distinct subspecies. Consistent with their common origin, whole-genome sequence comparisons have revealed extensive synteny among M. avium organisms. However, the sequenced strains also display numerous regions of heterogeneity that likely contribute to the diversity of the individual subspecies. Starting from a phylogenetic framework derived by multilocus sequence analysis, we examined the distribution of 25 large sequence polymorphisms across a panel of genetically defined M. avium strains. This distribution was most variable among M. avium subsp. hominissuis isolates. In contrast, M. avium subsp. paratuberculosis strains exhibited a characteristic profile, with all isolates containing a set of genomic insertions absent from other M. avium strains. The emergence of the pathogen from its putative M. avium subsp. hominissuis ancestor entailed the acquisition of approximately 125 kb of novel genetic material, followed by a second phase, characterized by reductive genomics. One genomic deletion is common to all isolates while additional deletions distinguish two major lineages of M. avium subsp. paratuberculosis. For the average strain, these losses total at least 38 kb (sheep lineage) to 90 kb (cattle lineage). This biphasic pattern of evolution, characterized by chromosomal gene acquisition with subsequent gene loss, describes the emergence of M. avium subsp. paratuberculosis and may serve as a general model for the origin of pathogenic mycobacteria.

* Corresponding author. Mailing address: Division of Infectious Diseases and Medical Microbiology, A5-156, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada. Phone: (514) 934-1934, x42815. Fax: (514) 934-8423. E-mail: marcel.behr{at}mcgill.ca

{triangledown} Published ahead of print on 21 November 2008.

{ddagger} Supplemental material for this article may be found at http://jb.asm.org/.

{dagger} D.C.A. and C.Y.T. contributed equally to this study.

§ Present address: Ontario Agency for Health Protection and Promotion, Public Health Laboratories Branch, Etobicoke, Ontario M9P 3T1, Canada.

Journal of Bacteriology, February 2009, p. 1018-1025, Vol. 191, No. 3
0021-9193/09/$08.00+0     doi:10.1128/JB.01340-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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