The population genetics of the CRISPR-Cas system in bacteria

细菌 CRISPR-Cas 系统的群体遗传学

• 批准号: 285672682
• 负责人: Professor Dr. Rolf Backofen
• 金额: --
• 依托单位: Mathematisches Institut
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/285672682?language=en
• 关键词: population; genetics; CRISPR; Cas; system

The CRISPR-Cas system (Clustered Regularly Interspaced Short Palindromic Repeats) is a prokaryiotic adaptive defense system against phages (virus) that is contained in most bacteria. Upon an initial virus infection of a bacterial cell, the viral DNA can be excised by Cas-proteins and built into the CRISPR array of spacer sequences. Successive infection with the same virus is now prevented as foreign DNA matching this spacer is targeted by proteins which cleave the recognized DNA. If a bacterium does not posses the right spacer/Cas combination and is attacked by a virus, the virus can spread and kill the bacterium.In our project we combine bioinformatics expertise and probabilistic modeling in order to obtain quantitative and reliable models for understanding the evolution of CRISPR arrays in closely related strains. Fundamental to our work is a bioinformatics analysis including assembly and classification (by Cas proteins) of available metagenomics data from sea water and the human gut. Modeling CRISPR evolution is either carried out neutrally, where novel spacer sequences enter the CRISPR array at random positions or at the leader-end of the array. More realistic scenarios build on the co-evolution of bacterium and virus. We extend (the analysis of) existing evolutionary models and aim at bringing together metagenomics data and population genetic models via a neutrality test and inference of horizontal gene transfer within the CRISPR-Cas system.

CRISPR-Cas系统（重复的规则间隔短回文重复序列）是一种针对细菌（病毒）的原核适应性防御系统，包含在大多数细菌中。在细菌细胞的初始病毒感染后，病毒DNA可以被Cas蛋白切除并构建到间隔序列的CRISPR阵列中。由于与该间隔区匹配的外源DNA被蛋白质切割识别的DNA作为靶向，因此可以防止相同病毒的连续感染。如果一个细菌没有正确的间隔区/Cas组合，并受到病毒的攻击，病毒可以传播和杀死细菌。在我们的项目中，我们结合联合收割机生物信息学专业知识和概率建模，以获得定量和可靠的模型，了解CRISPR阵列在密切相关的菌株的演变。我们工作的基础是生物信息学分析，包括来自海水和人类肠道的可用宏基因组数据的组装和分类（通过Cas蛋白）。CRISPR进化建模是中性进行的，其中新的间隔序列在随机位置或在阵列的前导端进入CRISPR阵列。更现实的情景建立在细菌和病毒的共同进化上。我们扩展了现有的进化模型，旨在通过CRISPR-Cas系统内水平基因转移的中性测试和推断，将宏基因组学数据和群体遗传模型结合在一起。