The complete genome sequence of Mycobacterium avium subspecies paratuberculosis
- Lingling Li*,†,‡,
- John P. Bannantine‡,§,
- Qing Zhang*,†,‡,
- Alongkorn Amonsin*,†,‡,
- Barbara J. May*,†,
- David Alt§,
- Nilanjana Banerji†,¶,
- Sagarika Kanjilal†,‡,¶, and
- Vivek Kapur*,†,‡,∥
- *Department of Microbiology, †Biomedical Genomics Center, and ¶Department of Medicine, University of Minnesota, St. Paul, MN 55108; and §National Animal Disease Center, U.S. Department of Agriculture–Agriculture Research Service, Ames, IA 50010
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Communicated by Harley W. Moon, Iowa State University, Ames, IA, July 13, 2005 (received for review March 18, 2005)
Abstract
We describe here the complete genome sequence of a common clone of Mycobacterium avium subspecies paratuberculosis (Map) strain K-10, the causative agent of Johne's disease in cattle and other ruminants. The K-10 genome is a single circular chromosome of 4,829,781 base pairs and encodes 4,350 predicted ORFs, 45 tRNAs, and one rRNA operon. In silico analysis identified >3,000 genes with homologs to the human pathogen, M. tuberculosis (Mtb), and 161 unique genomic regions that encode 39 previously unknown Map genes. Analysis of nucleotide substitution rates with Mtb homologs suggest overall strong selection for a vast majority of these shared mycobacterial genes, with only 68 ORFs with a synonymous to nonsynonymous substitution ratio of >2. Comparative sequence analysis reveals several noteworthy features of the K-10 genome including: a relative paucity of the PE/PPE family of sequences that are implicated as virulence factors and known to be immunostimulatory during Mtb infection; truncation in the EntE domain of a salicyl-AMP ligase (MbtA), the first gene in the mycobactin biosynthesis gene cluster, providing a possible explanation for mycobactin dependence of Map; and Map-specific sequences that are likely to serve as potential targets for sensitive and specific molecular and immunologic diagnostic tests. Taken together, the availability of the complete genome sequence offers a foundation for the study of the genetic basis for virulence and physiology in Map and enables the development of new generations of diagnostic tests for bovine Johne's disease.
Footnotes
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↵ ∥ To whom correspondence should be addressed. E-mail: vkapur{at}umn.edu.
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↵ ‡ L.L., J.P.B., Q.Z., A.A., S.K., and V.K. have a financial conflict of interest that results from a patent application that has been filed on some DNA sequences that are disclosed and discussed in the manuscript. The patent applications that have been filed are jointly owned by the University of Minnesota and the U.S. Department of Agriculture. As named inventors, these authors may potentially financially benefit from the commercialization of the technology. In addition, some of the technology disclosed in this paper has also been licensed to ANDX, Inc., a University of Minnesota based startup company focusing on the development of molecular diagnostic assays, in which S.K. and V.K. have financial interests and are cofounders.
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Author contributions: L.L., J.P.B., and V.K. designed research; L.L., J.P.B., Q.Z., A.A., B.J.M., D.A., N.B., and S.K. performed research; Q.Z. and A.A. contributed new reagents/analytic tools; L.L., J.P.B., Q.Z., A.A., B.J.M., S.K., and V.K. analyzed data; and L.L., B.J.M., S.K., and V.K. wrote the paper.
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Abbreviations: Map, Mycobacterium avium subspecies paratuberculosis; Mav, Mycobacterium avium; Mtb, Mycobacterium tuberculosis.
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Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AE016958).
- Copyright © 2005, The National Academy of Sciences
