首页> 外文期刊>Infection, Genetics and Evolution: Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases >Evolutionary pathway of the Beijing lineage of Mycobacterium tuberculosis based on genomic deletions and mutT genes polymorphisms
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Evolutionary pathway of the Beijing lineage of Mycobacterium tuberculosis based on genomic deletions and mutT genes polymorphisms

机译:基于基因组缺失和mutT基因多态性的结核分枝杆菌北京谱系的进化途径

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Among the genotypes that prevail in the modern spectrum of Mycobacterium tuberculosis strains, the Beijing genotype is the one that causes major concern, as it is geographically widespread and it is considered hypervirulent. Comparative genomic studies have shown that Beijing strains have principally evolved through mechanisms of deletion of chromosomal regions, designated regions of difference (RD), and mutations. In this paper, we aimed to determine the evolutionary history of Beijing strains through the analysis of polymorphisms generated by deletions of large specific sequences, i.e., RD105, RD181, RD150, and RD142, and by single nucleotide substitutions in genes mutT4 and mutT2, coding for DNA repair enzymes. Based on the molecular characteristics of a collection of Beijing strains recently isolated in Tuscany, Italy, we propose a phylogenetic reconstruction of the Beijing family. According to our model, the Beijing family evolved from a M. tuberculosis progenitor following deletion of the RD207 region, an event responsible for the loss of spacers 1-34 in the direct repeat (DR) locus. The major lineages of the Beijing family then evolved via subsequent deletions of regions RD105, RD181 and RD150. In the most ancient evolutionary lineages genes mutT4 and mutT2 were in wild type configuration; the mutT4 mutation was acquired subsequent to the RD181 deletion in a progenitor strain that, in turn, gave rise to a sublineage bearing the mutT2 mutation. Within the major branches of the Beijing family, deletion of additional spacers in the DR locus led to evolution of sublineages characterized by different spoligotypes. Our evolutionary model of the Beijing family provides a deeper framework than previously proposed for epidemiologic and phylogenetic studies of circulating M. tuberculosis Beijing strains, thus allowing a more systematic and comprehensive evaluation of the relevance of Beijing strain variability.
机译:在现代分枝杆菌菌株中流行的基因型中,北京基因型引起了人们的极大关注,因为它在地理上广泛分布并且被认为是高毒力的。比较基因组学研究表明,北京菌株主要是通过删除染色体区域,指定差异区域(RD)和突变的机制进化而来的。本文旨在通过分析大特异性序列RD105,RD181,RD150和RD142的缺失,以及mutT4和mutT2基因的单核苷酸取代产生的多态性,确定北京菌株的进化史。用于DNA修复酶。基于最近在意大利托斯卡纳分离出的北京菌株的分子特征,我们提出了北京家族的系统发育重建。根据我们的模型,Beijing家族从RD207区域缺失后由结核分枝杆菌祖细胞演变而来,这是造成直接重复(DR)基因座中间隔区1-34丢失的事件。北京家族的主要血统随后通过区域RD105,RD181和RD150的缺失而进化。在最古老的进化谱系中,mutT4和mutT2基因处于野生型结构。 mutT4突变是在祖细胞株中RD181缺失后获得的,继而产生了携带mutT2突变的亚系。在北京家族的主要分支中,DR基因座中其他间隔子的缺失导致以不同的嗜血型为特征的亚谱系的进化。我们北京家族的进化模型提供了比以前为流行的北京结核分枝杆菌菌株的流行病学和系统发育研究提出的更深层次的框架,从而可以更系统和更全面地评估北京菌株变异性的相关性。

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