Genetic features of Mycobacterium tuberculosis modern Beijing sublineage.
Genetic features of Mycobacterium tuberculosis modern Beijing sublineage.
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结核分枝杆菌现代北京亚系的遗传特征.
DOI：
10.1038/emi.2016.14
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发表时间：
2016-02-24
影响因子：
13.2
通讯作者：
Gao Q
中科院分区：
文献类型：
--
作者：
Liu Q;Luo T;Dong X;Sun G;Liu Z;Gan M;Wu J;Shen X;Gao Q
结核分枝杆菌（MTB）北京菌株因其在世界范围内的迅速出现和流行率不断上升而引起了人们的极大关注。大力开展北京毒株高毒力、耐药性、易传播等致病特征的研究。从系统发育上看，MTB北京家族分为现代亚系和古代亚系。与古代北京毒株相比，现代北京毒株表现出更强的毒力和更高的患病率，但这种差异的遗传基础仍不清楚。在这项研究中，通过分析先前发表的 1082 个 MTB 北京菌株的测序数据，我们确定了现代北京菌株中常见但古代北京菌株中不存在的基因变化。这些变化包括 44 个单核苷酸多态性 (SNP) 和两个短基因组缺失。通过生物信息学分析，我们证明这些基因变化很可能产生功能影响。例如，4个基因因过早终止突变或基因组缺失而发生移码，19个非同义SNP位于保守密码子中，所有非同义突变的调控网络显着富集。此外，位于启动子区域的三个SNP被证实可以改变下游基因的表达。我们的研究精确定义了现代北京菌株的遗传特征，并为未来的研究提供了有趣的线索，以阐明该亚系成功扩张的机制。对现代北京亚系分析的这些发现可以为我们提供一个模型来了解 MTB 致病性的动态。
Mycobacterium tuberculosis (MTB) Beijing strains have caused a great concern because of their rapid emergence and increasing prevalence in worldwide regions. Great efforts have been made to investigate the pathogenic characteristics of Beijing strains such as hypervirulence, drug resistance and favoring transmission. Phylogenetically, MTB Beijing family was divided into modern and ancient sublineages. Modern Beijing strains displayed enhanced virulence and higher prevalence when compared with ancient Beijing strains, but the genetic basis for this difference remains unclear. In this study, by analyzing previously published sequencing data of 1082 MTB Beijing isolates, we determined the genetic changes that were commonly present in modern Beijing strains but absent in ancient Beijing strains. These changes include 44 single-nucleotide polymorphisms (SNPs) and two short genomic deletions. Through bioinformatics analysis, we demonstrated that these genetic changes had high probability of functional effects. For example, 4 genes were frameshifted due to premature stop mutation or genomic deletions, 19 nonsynonymous SNPs located in conservative codons, and there is a significant enrichment in regulatory network for all nonsynonymous mutations. Besides, three SNPs located in promoter regions were verified to alter downstream gene expressions. Our study precisely defined the genetic features of modern Beijing strains and provided interesting clues for future researches to elucidate the mechanisms that underlie this sublineage's successful expansion. These findings from the analysis of the modern Beijing sublineage could provide us a model to understand the dynamics of pathogenicity of MTB.