阶段变化作为Mycobacterium tuberculosis复合体适应的主要机制
Roger Vargas1,2, Michael J Luna3, Luca Freschi2
1Center for Computational Biomedicine, Harvard Medical School, Boston, MA 02115.
概括
在Mycobacterium结核综合体 (MTBC) 基因的相变,由同聚合物通道中的插入/删除驱动,有助于细菌适应. 这项研究确定了适应性相变异,揭示了病毒性和宿主生存的切换机制.
科学领域:
- 基因组学就是基因组学.
- 微生物学 微生物学
- 进化生物学 进化生物学
背景情况:
- 在同聚合物通道 (HTs) 中通过插入和删除 (INDELs) 的相变调节细菌中的基因表达.
- 这种机制在Mycobacterium结核综合体 (MTBC) 适应中的作用仍然基本上未被描述.
研究的目的:
- 在MTBC中确定积极选择下的基因组区域和相变异.
- 为了研究MTBC进化阶段变化的适应意义.
主要方法:
- 分析了31,428种不同的临床MTBC分离物,以检测复发的INDEL事件.
- 在同聚合物区域内估计体外框架转移速率.
- 中性进化模拟以识别假定适应性的替代物和相变异.
- 试验验证一个相变体对毒性基因表达的影响.
主要成果:
- 12.4%的复发INDEL事件被确定为HTs中的相变异.
- 在HT的体外框架转移率估计是中性替代率的100倍.
- 4,098个替代物和45个相变体被发现在MTBC中具有假定适应性.
- 一种适应性相变体在实验中被证实可以改变espA的表达,espA是ESX-1毒性的关键媒介.
结论:
- 特别是在ESX-1系统内,MTBC的相变化有助于细菌的适应.
- 这种机制可以作为一个开关,平衡抗原性和宿主生存策略.
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