A Guild of 45 CRISPR-Associated (Cas) Protein Families and Multiple CRISPR/Cas Subtypes Exist in Prokaryotic Genomes

Haft, Daniel H.; Selengut, Jeremy; Mongodin, Emmanuel F.; Nelson, Karen E.

doi:10.1371/journal.pcbi.0010060

Title: A Guild of 45 CRISPR-Associated (Cas) Protein Families and Multiple CRISPR/Cas Subtypes Exist in Prokaryotic Genomes

Journal Article · Fri Nov 11 00:00:00 EST 2005 · PLoS Computational Biology (Online)

DOI:https://doi.org/10.1371/journal.pcbi.0010060· OSTI ID:1627178

Haft, Daniel H. ^[1]; Selengut, Jeremy ^[1]; Mongodin, Emmanuel F. ^[1]; Nelson, Karen E. ^[1]

The Inst. for Genomic Research, Rockville, MD (United States)

Clustered regularly interspaced short palindromic repeats (CRISPRs) are a family of DNA direct repeats found in many prokaryotic genomes. Repeats of 21–37 bp typically show weak dyad symmetry and are separated by regularly sized, nonrepetitive spacer sequences. Four CRISPR-associated (Cas) protein families, designated Cas1 to Cas4, are strictly associated with CRISPR elements and always occur near a repeat cluster. Some spacers originate from mobile genetic elements and are thought to confer ‘‘immunity’’ against the elements that harbor these sequences. In the present study, we have systematically investigated uncharacterized proteins encoded in the vicinity of these CRISPRs and found many additional protein families that are strictly associated with CRISPR loci across multiple prokaryotic species. Multiple sequence alignments and hidden Markov models have been built for 45 Cas protein families. These models identify family members with high sensitivity and selectivity and classify key regulators of development, DevR and DevS, in Myxococcus xanthus as Cas proteins. These identifications show that CRISPR/cas gene regions can be quite large, with up to 20 different, tandem-arranged cas genes next to a repeat cluster or filling the region between two repeat clusters. Distinctive subsets of the collection of Cas proteins recur in phylogenetically distant species and correlate with characteristic repeat periodicity. The analyses presented here support initial proposals of mobility of these units, along with the likelihood that loci of different subtypes interact with one another as well as with host cell defensive, replicative, and regulatory systems. It is evident from this analysis that CRISPR/cas loci are larger, more complex, and more heterogeneous than previously appreciated.

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Research Organization:: Inst. for Genomic Research, Rockville, MD (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: FG02-01ER63133; FG02-04ER63935; FG02-01ER63203

OSTI ID:: 1627178

Journal Information:: PLoS Computational Biology (Online), Vol. 1, Issue 6; ISSN 1553-7358

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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