Functional genetic variation in pe/ppe genes contributes to diversity in Mycobacterium tuberculosis lineages and potential interactions with the human host.
Functional genetic variation in pe/ppe genes contributes to diversity in Mycobacterium tuberculosis lineages and potential interactions with the human host.
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PE/PPE基因的功能遗传变异有助于结核分枝杆菌谱系的多样性以及与人宿主的潜在相互作用。
DOI：
10.3389/fmicb.2023.1244319
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发表时间：
2023
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
大约10%的结核分枝杆菌的编码潜力由两个知之甚少的基因家族组成，pe和ppe基因座，被认为参与宿主-病原体相互作用。它们的重复性质和高GC含量阻碍了序列分析，导致被排除在全基因组研究之外。了解pe/ppe家族的遗传多样性对于促进其转化为结核病预防和治疗工具的潜力至关重要。为了研究169个pe/ppe基因的遗传多样性，我们对代表7个不同谱系的M.结核和M.牛卡介苗。提取了个体pe/ppe基因序列，并研究了不同谱系的多样性和保守性。基于相对于H37 Rv的蛋白质序列保守性水平，将pe/ppe基因分为三组，发现>50%是保守的，其中pe_pgr和ppe_mptr亚家族中的indel是结构变异的主要驱动因素。在pe和pe_pgrs基因之间观察到基因重排，如重复和基因融合。谱系间多样性揭示了谱系特异性SNP和插入缺失。pe/ppe基因的高度保守性，以及谱系特异性的发现，表明它们的系统发育信息。然而，也发现了与参考文献不同的结构变体和基因重排，对致病性有潜在影响。总的来说，提高我们对这些复杂基因家族的认识可能会深入了解致病性，并为开发急需的结核病控制工具提供信息。
Around 10% of the coding potential of Mycobacterium tuberculosisis constituted by two poorly understood gene families, the pe and ppe loci, thought to be involved in host-pathogen interactions. Their repetitive nature and high GC content have hindered sequence analysis, leading to exclusion from whole-genome studies. Understanding the genetic diversity of pe/ppe families is essential to facilitate their potential translation into tools for tuberculosis prevention and treatment. To investigate the genetic diversity of the 169 pe/ppe genes, we performed a sequence analysis across 73 long-read assemblies representing seven different lineages of M. tuberculosis and M. bovis BCG. Individual pe/ppe gene alignments were extracted and diversity and conservation across the different lineages studied. The pe/ppe genes were classified into three groups based on the level of protein sequence conservation relative to H37Rv, finding that >50% were conserved, with indels in pe_pgrs and ppe_mptr sub-families being major drivers of structural variation. Gene rearrangements, such as duplications and gene fusions, were observed between pe and pe_pgrs genes. Inter-lineage diversity revealed lineage-specific SNPs and indels. The high level of pe/ppe genes conservation, together with the lineage-specific findings, suggest their phylogenetic informativeness. However, structural variants and gene rearrangements differing from the reference were also identified, with potential implications for pathogenicity. Overall, improving our knowledge of these complex gene families may have insights into pathogenicity and inform the development of much-needed tools for tuberculosis control.
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影响因子：
4.4
作者：
Reyes A;Sandoval A;Cubillos-Ruiz A;Varley KE;Hernández-Neuta I;Samper S;Martín C;García MJ;Ritacco V;López L;Robledo J;Zambrano MM;Mitra RD;Del Portillo P
通讯作者：
Del Portillo P
影响因子：
3.7
作者：
Homolka S;Ubben T;Niemann S
通讯作者：
Niemann S
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
--
作者：
Han, Seung Jung;Song, Taeksun;Shin, Sung Jae
通讯作者：
Shin, Sung Jae
影响因子：
4.4
作者：
McGuire AM;Weiner B;Park ST;Wapinski I;Raman S;Dolganov G;Peterson M;Riley R;Zucker J;Abeel T;White J;Sisk P;Stolte C;Koehrsen M;Yamamoto RT;Iacobelli-Martinez M;Kidd MJ;Maer AM;Schoolnik GK;Regev A;Galagan J
通讯作者：
Galagan J