结核分枝杆菌与牛分枝杆菌全基因组比较分析

The Comparative Analysis of the Whole-genome Sequences of Mycobacterium tuberculosis and Mycobacterium bovis

本研究旨在揭示结核分枝杆菌与牛分枝杆菌全基因组的遗传差异,为结核分枝杆菌与牛分枝杆菌的鉴别诊断提供新的分子标志。利用结核分枝杆菌H37Rv和牛分枝杆菌AF2122/97的全基因组测序结果,通过在线比对,完成了两者的全基因组比对分析。结果显示AF2122/97相对H37Rv存在14处大片段缺失,大小范围为0.8～12.7kb,其中RD18、RD19及RD20等3处缺失为首次报道。此外,AF2122/97还存在6处基因内部小片段的缺失,大小范围为12～714bp,其中Mb1319及Mb3293c基因内部缺失为首次报道。H37Rv相对AF2122/97存在6处大片段缺失,大小范围为1.3～5.4kb。此外,H37Rv还存在5处基因内部小片段的缺失,大小范围为10～48bp,这些基因的内部缺失都为首次报道。通过结核分枝杆菌H37Rv和牛分枝杆菌AF2122/97的全基因组序列比对,揭示了这2种菌株间的遗传差异,阐述影响表型特征、寄主偏好性及毒力差异的关键性遗传基础。这些新的认识将有助于开发新的药物、诊断试剂和疫苗。

The aim of present study was to reveal the comparative differences of whole-genome sequences between Mycobacterium tuberculosis and Mycobacterium bovis,and to provide new molecular markers for identification and diagnosis of these two bacilli.The whole-genome sequences of M.tuberculosis H37Rv and M.bovis AF2122/97were sequenced and their genomic comparison was performed by on-line tools.M.bovis AF2122/97shared 99.95%genomic nucleotides identity with M.tuberculosis H37Rv.14large fragment deletions varied in a range from 0.8to 12.7kb and 6small deletions varied from 12to 714bp were detected in AF2122/97strain by comparison with H37Rv,while 6large deletions ranged from 1.3to 5.4kb and 5small deletions ranged from 10to 48bp,in turn,were discovered in H37Rv strain.The large fragment deletions of RD18, RD19and RD20in AF2122/97strain,and all small deletions both in AF2122/97and H37Rv strains were firstly reported.Deletion has led to a reduced genome size of M.bovis.Most of the deleted genes are found to be responsible for encoding cell wall components and secreted proteins, indicating that deletions of these genes may contribute to host-bacillus interaction or immune evasion.The new understanding might be helpful in the development of new drugs,diagnostic reagents and vaccines.