Submitted to: Biomed Central (BMC) Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/15/2012
Publication Date: 3/12/2012
Citation: Bannantine, J.P., Wu, C., Hsu, C., Zhou, S., Schwartz, D.C., Bayles, D.O., Paustian, M.L., Alt, D.P., Sreevatsan, S., Kapur, V., Talaat, A.M. 2012. Genome sequencing of ovine isolates of Mycobacterium avium subspecies paratuberculosis offers insights into host association. Biomed Central (BMC) Genomics. 13:89. Available: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337245/pdf/1471-2164-13-89.pdf. Interpretive Summary: This study was performed to address the knowledge gap that exists on genetic differences between cattle strains of M. avium subspecies paratuberculosis (bacterium causing Johne’s disease) and sheep strains of this bacterium. It has been widely reported that there are differences, but exactly what they were remained a mystery. To solve this knowledge gap, the genome of a U.S. sheep isolate was sequenced. From this effort we identified a surprising number of deleted genes and inversions, where the DNA had been “flipped” or turned around in a segment of the genome. We also identified single nucleotide changes when compared the genomes of the cattle and sheep strains. The results can now be used to underpin the observable characteristics unique to each strain and understand why these strains have preferential hosts.
Technical Abstract: 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 whole genome of U.S. sheep isolates with the help of optical mapping. Our analysis of one of the isolates, S397 in its draft form, revealed a genome 4.8 Mb in size with 4,700 open reading frames (ORFs), including 17 copies of the IS900 insertion element. Comparative analysis of the sheep S397 isolate of MAP shows it acquired approximately 10 large sequence regions each containing four or more ORFs that are shared with M. avium subsp. hominissuis strain 104 and lost 2 large regions that are present in the bovine K-10 strain. Comparative analysis also revealed 105 ORFs missing in the S397 genome that are present in the K-10 genome. Conversely, the S397 sequence has 347 ORFs not present in K-10. In addition, optical mapping showed the presence of 7 large inversions between the bovine and ovine genomes that total nearly 2.65 Mb. Two additional sheep strains of MAP were also sequenced, JTC 1074 and JTC 7565. There were no gene differences among these three strains. Despite the overall similarity among the examined genomes from the ovine isolates, there were a few single nucleotide polymorphisms (N=75), precursors for further evolutionary scenarios among sheep isolates. Variations discovered in the ovine isolates of MAP will help in deciphering the phenotypic differences observed among sheep and cattle strains of MAP and could provide a more complete understanding of the genomic diversity associated with the infected hosts.