PDF(Pubmed)
Abstract：
UNASSIGNED: Tuberculosis (TB), mainly caused by Mycobacterium tuberculosis (Mtb), remains a serious public health problem. Increasing evidence supports that selective evolution is an important force affecting genomic determinants of Mtb phenotypes. It is necessary to further understand the Mtb selective evolution and identify the positively selected genes that probably drive the phenotype of Mtb.
UNASSIGNED: This study mainly focused on the positive selection of 807 Mtb 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 Mtb strains.
UNASSIGNED: 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 (gyrA, rpoB, rpoC, katG, pncA, embB, gid, and cut1) 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 cut1. There was a codon in Rv0336 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.
UNASSIGNED: This study revealed the ongoing selective evolution of Mtb. 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.
UNASSIGNED: This study mainly focused on the positive selection of 807 Mtb 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 Mtb strains.
UNASSIGNED: 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 (gyrA, rpoB, rpoC, katG, pncA, embB, gid, and cut1) 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 cut1. There was a codon in Rv0336 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.
UNASSIGNED: This study revealed the ongoing selective evolution of Mtb. 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.
摘要：
■结核病（TB），主要由结核分枝杆菌（Mtb）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Mtb表型的基因组决定因素的重要力量。有必要进一步了解Mtb的选择性进化并鉴定可能驱动Mtb表型的正选择基因。
■本研究主要集中于使用全基因组测序（WGS）对来自中国南疆的807Mtb菌株的阳性选择。PAML软件用于鉴定在807Mtb菌株中处于阳性选择下的基因和位点。
■谱系2(62.70%)菌株是该地区的优势菌株，其次是谱系3（19.45％）和谱系4（17.84％）菌株。47个基因中有239个密码子处于正选择状态,这些基因主要与转录功能相关，防御机制,和细胞壁/膜/包膜生物发生。八个基因中有28个密码子(43个突变)(gyrA，rpoB,rpoc,katG,pncA,embb,GID,和cut1）在多药耐药（MDR）菌株而非药物敏感（DS）菌株中的阳性选择下，其中27个突变是耐药基因座，9个突变为非耐药位点，但在耐药基因中，2个突变是代偿性突变，cut1耐药基因未知，有5个突变。在L3菌株的阳性选择下,在Rv0336中存在密码子,但在L2和L4菌株中没有。T细胞和B细胞的表位都是高度保守的，特别是在T细胞表位中。
■这项研究揭示了Mtb的持续选择性进化。我们发现了一些特殊的基因和位点处于正选择状态，这可能有助于MDR和L3菌株的优势。有必要进一步研究这些突变，以了解其对表型的影响，为开发新的结核病干预措施提供更多有用的信息。
■本研究主要集中于使用全基因组测序（WGS）对来自中国南疆的807Mtb菌株的阳性选择。PAML软件用于鉴定在807Mtb菌株中处于阳性选择下的基因和位点。
■谱系2(62.70%)菌株是该地区的优势菌株，其次是谱系3（19.45％）和谱系4（17.84％）菌株。47个基因中有239个密码子处于正选择状态,这些基因主要与转录功能相关，防御机制,和细胞壁/膜/包膜生物发生。八个基因中有28个密码子(43个突变)(gyrA，rpoB,rpoc,katG,pncA,embb,GID,和cut1）在多药耐药（MDR）菌株而非药物敏感（DS）菌株中的阳性选择下，其中27个突变是耐药基因座，9个突变为非耐药位点，但在耐药基因中，2个突变是代偿性突变，cut1耐药基因未知，有5个突变。在L3菌株的阳性选择下,在Rv0336中存在密码子,但在L2和L4菌株中没有。T细胞和B细胞的表位都是高度保守的，特别是在T细胞表位中。
■这项研究揭示了Mtb的持续选择性进化。我们发现了一些特殊的基因和位点处于正选择状态，这可能有助于MDR和L3菌株的优势。有必要进一步研究这些突变，以了解其对表型的影响，为开发新的结核病干预措施提供更多有用的信息。
