Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination
Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination
复制标题
DOI：
10.1073/pnas.94.18.9869
复制
发表时间：
1997-09-02
影响因子：
11.1
通讯作者：
Musser, JM
中科院分区：
文献类型：
--
作者：
Sreevatsan, S;Pan, X;Musser, JM
三分之一的人类感染了结核病的病原体--结核分枝杆菌。对全球回收的26个结构基因或基因座中的两个百万碱基的序列分析发现，与其他人类细菌病原体相比，沉默的核苷酸替换显著减少。结构基因缺乏中性突变表明，结核分枝杆菌在进化上还很年轻，最近已经在全球范围内传播。物种多样性在很大程度上是由快速进化的插入序列引起的，这意味着移动元件的移动是产生该病原体基因组变异的一个基本过程。根据编码过氧化氢酶-过氧化物酶和旋转酶A亚单位基因的两个高频率多态，鉴定了三个结核分枝杆菌的遗传群体。第一类生物在进化上是古老的，与引起牛结核病的牛分枝杆菌同源。该基因群的几个不同插入序列IS6110亚型的子集在相同的染色体插入位置整合了IS6110，该插入位点位于包含复制起始区的dna A和dna N之间。值得注意的是，对休斯顿和纽约市地区患者的近6000个分离株的研究发现，48个相对较大的病例群中有47个是由基因类型1和2引起的，而不是由3组生物引起的。观察到新出现的第3组生物与散发性病例有关，而不是聚集性病例，这表明病原体正在向降低传播力或毒力的状态进化。
One-third of humans are infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. Sequence analysis of two megabases in 26 structural genes or loci in strains recovered globally discovered a striking reduction of silent nucleotide substitutions compared with other human bacterial pathogens. The lack of neutral mutations in structural genes indicates that M. tuberculosis is evolutionarily young and has recently spread globally. Species diversity is largely caused by rapidly evolving insertion sequences, which means that mobile element movement is a fundamental process generating genomic variation in this pathogen. Three genetic groups of M. tuberculosis were identified based on two polymorphisms that occur at high frequency in the genes encoding catalase-peroxidase and the A subunit of gyrase. Group 1 organisms are evolutionarily old and allied with M. bovis, the cause of bovine tuberculosis. A subset of several distinct insertion sequence IS6110 subtypes of this genetic group have IS6110 integrated at the identical chromosomal insertion site, located between dnaA and dnaN in the region containing the origin of replication. Remarkably, study of approximate to 6,000 isolates from patients in Houston and the New York City area discovered that 47 of 48 relatively large case clusters were caused by genotypic group 1 and 2 but not group 3 organisms. The observation that the newly emergent group 3 organisms are associated with sporadic rather than clustered cases suggests that the pathogen is evolving toward a state of reduced transmissability or virulence.