Analysis of the genetic variation in Mycobacterium tuberculosis strains by multiple genome alignments.
Analysis of the genetic variation in Mycobacterium tuberculosis strains by multiple genome alignments.
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DOI：
10.1186/1756-0500-1-110
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发表时间：
2008-11-07
影响因子：
1.8
通讯作者：
Zambrano, Maria Mercedes
中科院分区：
文献类型：
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作者：
Cubillos-Ruiz, Andres;Morales, Juan;Zambrano, Maria Mercedes
最近几个结核分枝杆菌（MTB）基因组的完整核苷酸序列的测定允许使用比较基因组学作为一种工具，用于解剖的性质和后果，在这个物种的遗传变异。临床菌株（CDC 1551，F11，哈勒姆和C）的基因组沿着实验室菌株（H37 Rv和H37 Ra）的基因组的多重比对，为这种细菌适应人类宿主的机制提供了新的见解。在6个M.结核菌株不涉及显著的基因组重排。大多数的变化结果从删除和转座事件优先与插入序列和基因的PE/PPE家庭，但不与基因的毒力。使用基于Perl的软件islandsanalyser，它创建了基因组中遗传变异的表示，我们确定了基因组中多态性分布和频率模式的差异。显示菌株特异性多态性的基因的鉴定和菌株特异性多态性的数量外推到无限数量的基因组表明，不同的菌株含有有限数量的独特多态性。多个基因组的比较表明，M。结核病基因组目前正在经历一个活跃的基因衰变过程，类似于专性细菌共生体的适应过程。这一观察结果为这种细菌的进化和致病机理的理解开辟了新的视角。
The recent determination of the complete nucleotide sequence of several Mycobacterium tuberculosis (MTB) genomes allows the use of comparative genomics as a tool for dissecting the nature and consequence of genetic variability within this species. The multiple alignment of the genomes of clinical strains (CDC1551, F11, Haarlem and C), along with the genomes of laboratory strains (H37Rv and H37Ra), provides new insights on the mechanisms of adaptation of this bacterium to the human host. The genetic variation found in six M. tuberculosis strains does not involve significant genomic rearrangements. Most of the variation results from deletion and transposition events preferentially associated with insertion sequences and genes of the PE/PPE family but not with genes implicated in virulence. Using a Perl-based software islandsanalyser, which creates a representation of the genetic variation in the genome, we identified differences in the patterns of distribution and frequency of the polymorphisms across the genome. The identification of genes displaying strain-specific polymorphisms and the extrapolation of the number of strain-specific polymorphisms to an unlimited number of genomes indicates that the different strains contain a limited number of unique polymorphisms. The comparison of multiple genomes demonstrates that the M. tuberculosis genome is currently undergoing an active process of gene decay, analogous to the adaptation process of obligate bacterial symbionts. This observation opens new perspectives into the evolution and the understanding of the pathogenesis of this bacterium.