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2015 ; 1311
(ä): 47-75
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Annotation and Classification of CRISPR-Cas Systems
#MMPMID25981466
Makarova KS
; Koonin EV
Methods Mol Biol
2015[]; 1311
(ä): 47-75
PMID25981466
show ga
The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas
(CRISPR-associated proteins) is a prokaryotic adaptive immune system that is
represented in most archaea and many bacteria. Among the currently known
prokaryotic defense systems, the CRISPR-Cas genomic loci show unprecedented
complexity and diversity. Classification of CRISPR-Cas variants that would
capture their evolutionary relationships to the maximum possible extent is
essential for comparative genomic and functional characterization of this
theoretically and practically important system of adaptive immunity. To this end,
a multipronged approach has been developed that combines phylogenetic analysis of
the conserved Cas proteins with comparison of gene repertoires and arrangements
in CRISPR-Cas loci. This approach led to the current classification of CRISPR-Cas
systems into three distinct types and ten subtypes for each of which signature
genes have been identified. Comparative genomic analysis of the CRISPR-Cas
systems in new archaeal and bacterial genomes performed over the 3 years elapsed
since the development of this classification makes it clear that new types and
subtypes of CRISPR-Cas need to be introduced. Moreover, this classification
system captures only part of the complexity of CRISPR-Cas organization and
evolution, due to the intrinsic modularity and evolutionary mobility of these
immunity systems, resulting in numerous recombinant variants. Moreover, most of
the cas genes evolve rapidly, complicating the family assignment for many Cas
proteins and the use of family profiles for the recognition of CRISPR-Cas subtype
signatures. Further progress in the comparative analysis of CRISPR-Cas systems
requires integration of the most sensitive sequence comparison tools, protein
structure comparison, and refined approaches for comparison of gene
neighborhoods.