Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains.
Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains.
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DOI：
10.1186/gb-2007-8-6-r102
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发表时间：
2007
期刊：
影响因子：
12.3
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中科院分区：
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--
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．对非致病性土拉菌亚种novicida U112进行测序，并与两个致病性亚种进行比较，为这些物种的致病性进化提供了见解。土拉菌弗朗西斯菌亚种土拉菌和全北极菌对人类具有致病性，而另外两个亚种，新菌和mediasiatica很少引起疾病。为了揭示土拉菌亚种和全北极菌亚种对人类致病的因素，我们将它们的基因组序列与对人类无致病性的土拉菌弗朗西斯菌亚种novicida U112的基因组序列进行了比较。将人致病性Francisella菌株的基因组与U112的基因组进行比较，发现了人致病性菌株特有的基因，并揭示了以前未发现的假基因。此外，这一分析提供了在人类致病菌株出现期间发生的进化事件的粗略年表。在人类致病菌株与非致病菌株分化期间和之后，在插入序列（IS元件）水平上的基因组重排、点突变和小缺失发生，导致基因失活。事件的年表表明遗传漂变在Francisella基因组中假基因形成中的重要作用。然而，在进化早期发生的突变可能已经在种群中固定下来，要么是因为进化瓶颈，要么是因为它们具有致病适应性（在感染的情况下有益）。由于Francisella的基因组结构与其他新兴或高致病性细菌的基因组相似，这种进化情景可能与其他物种的病原体共享。
.Sequencing of the non-pathogenic Francisella tularensis sub-species novicida U112, and comparison with two pathogenic sub-species, provides insights into the evolution of pathogenicity in these species. Francisella tularensis subspecies tularensis and holarctica are pathogenic to humans, whereas the two other subspecies, novicida and mediasiatica, rarely cause disease. To uncover the factors that allow subspecies tularensis and holarctica to be pathogenic to humans, we compared their genome sequences with the genome sequence of Francisella tularensis subspecies novicida U112, which is nonpathogenic to humans. Comparison of the genomes of human pathogenic Francisella strains with the genome of U112 identifies genes specific to the human pathogenic strains and reveals pseudogenes that previously were unidentified. In addition, this analysis provides a coarse chronology of the evolutionary events that took place during the emergence of the human pathogenic strains. Genomic rearrangements at the level of insertion sequences (IS elements), point mutations, and small indels took place in the human pathogenic strains during and after differentiation from the nonpathogenic strain, resulting in gene inactivation. The chronology of events suggests a substantial role for genetic drift in the formation of pseudogenes in Francisella genomes. Mutations that occurred early in the evolution, however, might have been fixed in the population either because of evolutionary bottlenecks or because they were pathoadaptive (beneficial in the context of infection). Because the structure of Francisella genomes is similar to that of the genomes of other emerging or highly pathogenic bacteria, this evolutionary scenario may be shared by pathogens from other species.