Pan-Genomic Study of Mycobacterium tuberculosis Reflecting the Primary/Secondary Genes, Generality/Individuality, and the Interconversion Through Copy Number Variations.
Pan-Genomic Study of Mycobacterium tuberculosis Reflecting the Primary/Secondary Genes, Generality/Individuality, and the Interconversion Through Copy Number Variations.
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结核分枝杆菌泛基因组研究反映初级/次级基因、通用性/个体性以及拷贝数变异的相互转换
DOI：
10.3389/fmicb.2018.01886
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发表时间：
2018
影响因子：
5.2
通讯作者：
Chen F
中科院分区：
文献类型：
--
作者：
Yang T;Zhong J;Zhang J;Li C;Yu X;Xiao J;Jia X;Ding N;Ma G;Wang G;Yue L;Liang Q;Sheng Y;Sun Y;Huang H;Chen F
自 2014 年以来，结核病 (TB) 已超过艾滋病毒，成为全球头号传染病杀手。主要病原体结核分枝杆菌 (Mtb) 包含约 4,000 个基因，约占基因组的 90%。然而，目前还不清楚这些基因中哪些是主要/次要的，哪些负责通用性/个体性，以及哪些在进化过程中相互转换。在这里，我们利用 36 个 Mtb 基因组的泛基因组分析来解决这些问题。我们鉴定了 3,679 个 Mtb 核心（即初级）基因，确定了它们的表型一般性（例如毒力、生长缓慢、休眠）。我们还观察到 1,122 个可有可无的次要基因和 964 个品系特异性次要基因，反映了部分共享和谱系/品系特异性的个体。其中，5个L2谱系特异性基因可能与L2谱系毒力增加有关。值得注意的是，我们发现了 28 个 Mtb“超级核心基因”（SCG：至少 90% 的菌株中有多个拷贝），这可能越来越重要，并反映了“超级表型的普遍性”。大多数 SCG 编码 PE/PPE、毒力因子、抗原和转座酶，并已被证实在 Mtb 致病性中发挥关键作用。对 28 个 SCG 的进一步研究表明，SCG、单拷贝核心、可有可无和品系特异性基因之间在进化过程中通过拷贝数变异 (CNV) 进行相互转换；不同拷贝上的不同突变凸显了结核分枝杆菌谱系之间微妙的适应性进化调节。这反映出基因的重要性因CNV而异，这可能是由环境/宿主适应的选择压力驱动的。此外，与牛分枝杆菌（Mbo）相比，Mtb拥有48个特异的单核心基因，部分反映了Mtb和Mbo个体的差异。
Tuberculosis (TB) has surpassed HIV as the leading infectious disease killer worldwide since 2014. The main pathogen, Mycobacterium tuberculosis (Mtb), contains ~4,000 genes that account for ~90% of the genome. However, it is still unclear which of these genes are primary/secondary, which are responsible for generality/individuality, and which interconvert during evolution. Here we utilized a pan-genomic analysis of 36 Mtb genomes to address these questions. We identified 3,679 Mtb core (i.e., primary) genes, determining their phenotypic generality (e.g., virulence, slow growth, dormancy). We also observed 1,122 dispensable and 964 strain-specific secondary genes, reflecting partially shared and lineage-/strain-specific individualities. Among which, five L2 lineage-specific genes might be related to the increased virulence of the L2 lineage. Notably, we discovered 28 Mtb “Super Core Genes” (SCGs: more than a copy in at least 90% strains), which might be of increased importance, and reflected the “super phenotype generality.” Most SCGs encode PE/PPE, virulence factors, antigens, and transposases, and have been verified as playing crucial roles in Mtb pathogenicity. Further investigation of the 28 SCGs demonstrated the interconversion among SCGs, single-copy core, dispensable, and strain-specific genes through copy number variations (CNVs) during evolution; different mutations on different copies highlight the delicate adaptive-evolution regulation amongst Mtb lineages. This reflects that the importance of genes varied through CNVs, which might be driven by selective pressure from environment/host-adaptation. In addition, compared with Mycobacterium bovis (Mbo), Mtb possesses 48 specific single core genes that partially reflect the differences between Mtb and Mbo individuality.
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影响因子：
5.4
作者：
Jackson, Mary
通讯作者：
Jackson, Mary
影响因子：
5.2
作者：
Khubaib M;Sheikh JA;Pandey S;Srikanth B;Bhuwan M;Khan N;Hasnain SE;Ehtesham NZ
通讯作者：
Ehtesham NZ
影响因子：
5.2
作者：
Forrellad MA;Klepp LI;Gioffré A;Sabio y García J;Morbidoni HR;de la Paz Santangelo M;Cataldi AA;Bigi F
通讯作者：
Bigi F
DOI：
10.1073/pnas.1409345111
发表时间：
2014-10-14
影响因子：
11.1
作者：
Ekiert, Damian C.;Cox, Jeffery S.
通讯作者：
Cox, Jeffery S.
DOI：
10.1073/pnas.1406693111
发表时间：
2014-08-05
影响因子：
11.1
作者：
Gonzalo-Asensio, Jesus;Malaga, Wladimir;Guilhot, Christophe
通讯作者：
Guilhot, Christophe