National Animal Disease Center, USDA-Agricultural Research Service, Ames, Iowa, USA.
BMC Genomics. 2012 Mar 12;13:89. doi: 10.1186/1471-2164-13-89.
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.
牛分枝杆菌副结核亚种（MAP）的基因组在牛、人类和野生动物分离株的基因组中非常相似。然而，我们实验室之前对牛 K-10 株的研究表明，与绵羊分离株相比存在很大差异。为了系统地描述可能与特定宿主相关的所有基因组差异，我们对 3 株美国绵羊分离株进行了测序，并获得了光学图谱。
我们对其中一个分离株 MAP S397 的分析表明，其基因组大小为 4.8Mb，包含 4700 个开放阅读框（ORFs）。对 MAP S397 分离株的比较分析表明，它获得了大约 10 个与人类分枝杆菌亚种同源人菌株 104 共享的大序列区域，并丢失了存在于牛株中的 2 个大区域。此外，光学图谱定义了牛和羊基因组之间存在 7 个大的倒位（约 2.36Mb）。对另外 2 株绵羊分枝杆菌（JTC1074 和 JTC7565）的全基因组测序进一步证实了绵羊分离株的基因组同源性，尽管在核苷酸水平上存在多态性。
这里采用的比较序列分析提供了对宿主关联、分枝杆菌属复合种群成员进化的更好理解，并有助于解释在绵羊和牛分枝杆菌中观察到的表型差异。基于全基因组测序结合光学图谱的类似方法可用于研究密切相关的病原体。我们根据这些基因组序列提出了分枝杆菌属复合种群菌株的进化情景。
