Taxonomic Distribution, Phylogenetic Relationship, and Domain Conservation of CRISPR-Associated Cas Proteins.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a naturally occurring genetic defense system in bacteria and archaea. It is comprised of a series of DNA sequence repeats with spacers derived from previous exposures to plasmid or phage. Further understanding and applications of CRISPR system have revolutionized our capacity for gene or genome editing of prokaryotes and eukaryotes. The CRISPR systems are classified into 3 distinct types: type I, type II, and type III, each of which possesses an associated signature protein, Cas3, Cas9, and Cas10, respectively. As the CRISPR loci originated from earlier independent exposures of foreign genetic elements, it is likely that their associated signature proteins may have evolved rapidly. Also, their functional domain structures might have experienced different selective pressures, and therefore, they have differentially diverged in their amino acid sequences. We employed genomic, phylogenetic, and structure-function constraint analyses to reveal the evolutionary distribution, phylogenetic relationship, and structure-function constraints of Cas3, Cas9, and Cas10 proteins. Results reveal that all 3 Cas-associated proteins are highly represented in the phyla