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

By Daniel H. Haft, Jeremy D. Selengut, E. Mongodin, K. Nelson. PLoS Comput. Biol., 2005

1,008 citations recorded by the source corpus.

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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/13782077413f3a947087be17e3f5425c95c1287b

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Citations in the corpus

Type III CRISPR-Cas Systems: Deciphering the Most Complex Prokaryotic Immune System (2021, background): “performed an extensive search and classification of pro tein coding genes located in the vicinity of CRISPR arrays and delineated the organization of these genes in specific loci [9].”
Genomics of bacteria and archaea: the emerging dynamic view of the prokaryotic world (2008, background): “complex (90) and the Cas genes that comprise an antivirus defense system (see also below) (89,91,92).”
Interference by clustered regularly interspaced short palindromic repeat (CRISPR) RNA is governed by a seed sequence (2011, background): “CRISPR cassettes are often flanked by a diverse set of CRISPR-associated (cas) genes (2, 5, 6).”
MacSyFinder: A Program to Mine Genomes for Molecular Systems with an Application to CRISPR-Cas Systems (2014, methodology): “Among the 89 profiles available, 53 were constructed by Haft and colleagues [24] and correspond to 45 Cas protein families that were used to propose a CRISPR-Cas systems classification [25].”
CRISPRFinder: a web tool to identify clustered regularly interspaced short palindromic repeats (2007, background): “In a genome, a single CRISPR is generally associated with a family of genes called cas for CRISPR-associated (8,12), encoding proteins showing functional similarity with components of the eukaryotic RNA interference (RNAi) systems (13).”
RNA-Guided RNA Cleavage by a CRISPR RNA-Cas Protein Complex (2009, positive): “There are 6 cmr genes: cmr2 encodes a predicted polymerase with HD nuclease domains, and cmr1, cmr3, cmr4, and cmr6 encode repeat-associated mysterious proteins (RAMPs) (Makarova et al., 2002; Haft et al., 2005).”
Development and Applications of CRISPR-Cas9 for Genome Engineering (2014, positive): “At the same time, several clusters of signature CRISPR-associated (cas) genes were identified to be well conserved and typically adjacent to the repeat elements (Jansen et al., 2002), serving as a basis for the eventual classification of three different types of CRISPR systems (types I–III) (Haft et”
Phage Response to CRISPR-Encoded Resistance in Streptococcus thermophilus (2007, background): “We thank Denise Tremblay, Simon Labrie, and Julie Samson for stimulating discussions; Yanick Bourbeau for the DNA display conception; and Gene Bourgeau for editorial assistance.”
Ecology of marine Bacteroidetes: a comparative genomics approach (2013, background): “The latter are repetitive palindromic sequences that, in association with genes cas7, cas5 and two cas3 (also present), serve a defensive function against phages and can be mobilized by horizontal gene transfer (Haft et al., 2005).”
Short motif sequences determine the targets of the prokaryotic CRISPR defence system. (2009, background): “While a large guild (25–45 families) of CAS genes has been found (Haft et al., 2005; Jansen et al., 2002; Makarova et al., 2006), only motifs of cas1 and cas2 (core genes) are present in the nine different types of CAS operons.”