The population genetics of the CRISPR-Cas system in bacteria

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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.