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Genome sequencing of ovine isolates of Mycobacterium avium subspecies paratuberculosis offers insights into host association

John P Bannantine1*, Chia-wei Wu2, Chungyi Hsu2, Shiguo Zhou3, David C Schwartz3, Darrell O Bayles1, Michael L Paustian1, David P Alt1, Srinand Sreevatsan4, Vivek Kapur5 and Adel M Talaat26*

Author Affiliations

1 National Animal Disease Center, USDA-Agricultural Research Service, Ames, Iowa, USA

2 The Laboratory of Bacterial Genomics, Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA

3 Laboratory for Molecular and Computational Genomics, Department of Chemistry and Laboratory of Genetics, UW Biotechnology Center, University of Wisconsin-Madison, Madison, Wisconsin, USA

4 Department of Veterinary Population Medicine and Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, USA

5 Department of Veterinary and Biomedical Sciences and Huck Institutes of the Life Sciences, Penn State University, University Park, Pennsylvania, USA

6 Department of Food Hygiene, Cairo University, Cairo, Egypt

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BMC Genomics 2012, 13:89  doi:10.1186/1471-2164-13-89

Published: 12 March 2012



The genome of Mycobacterium avium subspecies paratuberculosis (MAP) is remarkably homogeneous among the genomes of bovine, human and wildlife isolates. However, previous work in our laboratories with the bovine K-10 strain has revealed substantial differences compared to sheep isolates. To systematically characterize all genomic differences that may be associated with the specific hosts, we sequenced the genomes of three U.S. sheep isolates and also obtained an optical map.


Our analysis of one of the isolates, MAP S397, revealed a genome 4.8 Mb in size with 4,700 open reading frames (ORFs). Comparative analysis of the MAP S397 isolate showed it acquired approximately 10 large sequence regions that are shared with the human M. avium subsp. hominissuis strain 104 and lost 2 large regions that are present in the bovine strain. In addition, optical mapping defined the presence of 7 large inversions between the bovine and ovine genomes (~ 2.36 Mb). Whole-genome sequencing of 2 additional sheep strains of MAP (JTC1074 and JTC7565) further confirmed genomic homogeneity of the sheep isolates despite the presence of polymorphisms on the nucleotide level.


Comparative sequence analysis employed here provided a better understanding of the host association, evolution of members of the M. avium complex and could help in deciphering the phenotypic differences observed among sheep and cattle strains of MAP. A similar approach based on whole-genome sequencing combined with optical mapping could be employed to examine closely related pathogens. We propose an evolutionary scenario for M. avium complex strains based on these genome sequences.

M. paratuberculosis; Evolution; Johne's disease; Genome; Optical mapping