Deng Lele, Wang Quan, Liu Haican, Jiang Yi, Xu Miao, Xiang Yu, Yang Ting, Yang Shuliu, Yan Di, Li Machao, Zhao Lili, Zhao Xiuqin, Wan Kanglin, He Guangxue, Mijiti Xiaokaiti, Li Guilian
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Front Microbiol. 2024 Apr 15;15:1290227. doi: 10.3389/fmicb.2024.1290227. eCollection 2024.
Tuberculosis (TB), mainly caused by (), remains a serious public health problem. Increasing evidence supports that selective evolution is an important force affecting genomic determinants of phenotypes. It is necessary to further understand the selective evolution and identify the positively selected genes that probably drive the phenotype of .
This study mainly focused on the positive selection of 807 strains from Southern Xinjiang of China using whole genome sequencing (WGS). PAML software was used for identifying the genes and sites under positive selection in 807 strains.
Lineage 2 (62.70%) strains were the dominant strains in this area, followed by lineage 3 (19.45%) and lineage 4 (17.84%) strains. There were 239 codons in 47 genes under positive selection, and the genes were majorly associated with the functions of transcription, defense mechanisms, and cell wall/membrane/envelope biogenesis. There were 28 codons (43 mutations) in eight genes (, , , , , , , and ) under positive selection in multi-drug resistance (MDR) strains but not in drug-susceptible (DS) strains, in which 27 mutations were drug-resistant loci, 9 mutations were non-drug-resistant loci but were in drug-resistant genes, 2 mutations were compensatory mutations, and 5 mutations were in unknown drug-resistant gene of . There was a codon in under positive selection in L3 strains but not in L2 and L4 strains. The epitopes of T and B cells were both hyper-conserved, particularly in the T-cell epitopes.
This study revealed the ongoing selective evolution of . We found some special genes and sites under positive selection which may contribute to the advantage of MDR and L3 strains. It is necessary to further study these mutations to understand their impact on phenotypes for providing more useful information to develop new TB interventions.
结核病（TB）主要由（）引起，仍然是一个严重的公共卫生问题。越来越多的证据支持选择性进化是影响表型基因组决定因素的重要力量。有必要进一步了解（）的选择性进化，并鉴定可能驱动（）表型的正选择基因。
本研究主要利用全基因组测序（WGS）对来自中国新疆南部的807株（）菌株进行正选择分析。使用PAML软件鉴定807株（）菌株中处于正选择的基因和位点。
2系（62.70%）菌株是该地区的优势菌株，其次是3系（19.45%）和4系（17.84%）菌株。有47个基因中的239个密码子处于正选择状态，这些基因主要与转录、防御机制以及细胞壁/膜/包膜生物合成功能相关。在多药耐药（MDR）菌株中有8个基因（，，，，，，，和）中的28个密码子（43个突变）处于正选择状态，而在药物敏感（DS）菌株中未出现，其中27个突变是耐药位点，9个突变是非耐药位点但位于耐药基因中，2个突变是补偿性突变，5个突变位于（）未知的耐药基因中。在L3菌株中有一个密码子处于正选择状态，而在L2和L4菌株中未出现。T细胞和B细胞表位均高度保守，尤其是在T细胞表位中。
本研究揭示了（）正在进行的选择性进化。我们发现了一些处于正选择状态的特殊基因和位点，它们可能有助于MDR和L3菌株的优势。有必要进一步研究这些突变以了解它们对表型的影响，从而为开发新的结核病干预措施提供更多有用信息。
