Modularity and Hierarchy in CRISPR-Cas Target Recognition

Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) constitute a unique and highly adaptive immune system in prokaryotes. Sequences from invading mobile genetic elements, such as bacteriophage, are incorporated into the CRISPR locus to generate a heritable, immunological memory. We have reviewed a large body of CRISPR-Cas research to explore themes of co- evolutionary dynamics, horizontal gene transfer, specificity and cross-reactivity, cost and regulation, non-immunological CRISPR functions that boost host cell robust- ness, as well as applicable mechanisms for efficient and specific genetic engineering. We have also developed a model to show that the CRISPR-Cas machinery evolved with selection for modularity and hierarchy in order to effectively recognize invaders. Physical understanding of the CRISPR-Cas system, especially the specificity of target recognition, will advance uses in biotechnology.