The population genetics of the CRISPR-Cas system in bacteria

CRISPR-Cas系统（Clustered Regularly Interspaced Short Palindromic Repeats）是一种针对噬菌体（病毒）的原核生物适应性防御系统，大多数细菌都含有噬菌体（病毒）。当病毒初次感染细菌细胞时，病毒DNA可以被cas蛋白切除，并被植入间隔序列的CRISPR阵列中。由于与该间隔物匹配的外来DNA被蛋白质靶向，从而切割已识别的DNA，因此可以防止同一病毒的连续感染。如果细菌不具备正确的间隔物/Cas组合并受到病毒的攻击，病毒就会传播并杀死细菌。在我们的项目中，我们将生物信息学专业知识与概率建模相结合，以获得定量和可靠的模型，以了解密切相关菌株中CRISPR阵列的进化。我们工作的基础是生物信息学分析，包括从海水和人类肠道中获得的宏基因组数据的组装和分类（通过Cas蛋白）。CRISPR进化的建模要么中性地进行，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。更现实的场景建立在细菌和病毒的共同进化之上。我们扩展（分析）现有的进化模型，旨在通过中性测试和推断CRISPR-Cas系统内的水平基因转移，将宏基因组学数据和群体遗传模型结合在一起。

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.