Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems

<p>Abstract</p> <p>Background</p> <p>The CRISPR-Cas adaptive immunity systems that are present in most Archaea and many Bacteria function by incorporating fragments of alien genomes into specific genomic loci, transcribing the inserts and using the transcripts as guide...

Full description

Bibliographic Details
Main Authors: Wolf Yuri I, Aravind L, Makarova Kira S, Koonin Eugene V
Format: Article
Language:English
Published: BMC 2011-07-01
Series:Biology Direct
Online Access:http://www.biology-direct.com/content/6/1/38
_version_ 1811316127152734208
author Wolf Yuri I
Aravind L
Makarova Kira S
Koonin Eugene V
author_facet Wolf Yuri I
Aravind L
Makarova Kira S
Koonin Eugene V
author_sort Wolf Yuri I
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>The CRISPR-Cas adaptive immunity systems that are present in most Archaea and many Bacteria function by incorporating fragments of alien genomes into specific genomic loci, transcribing the inserts and using the transcripts as guide RNAs to destroy the genome of the cognate virus or plasmid. This RNA interference-like immune response is mediated by numerous, diverse and rapidly evolving Cas (CRISPR-associated) proteins, several of which form the Cascade complex involved in the processing of CRISPR transcripts and cleavage of the target DNA. Comparative analysis of the Cas protein sequences and structures led to the classification of the CRISPR-Cas systems into three Types (I, II and III).</p> <p>Results</p> <p>A detailed comparison of the available sequences and structures of Cas proteins revealed several unnoticed homologous relationships. The Repeat-Associated Mysterious Proteins (RAMPs) containing a distinct form of the RNA Recognition Motif (RRM) domain, which are major components of the CRISPR-Cas systems, were classified into three large groups, Cas5, Cas6 and Cas7. Each of these groups includes many previously uncharacterized proteins now shown to adopt the RAMP structure. Evidence is presented that large subunits contained in most of the CRISPR-Cas systems could be homologous to Cas10 proteins which contain a polymerase-like Palm domain and are predicted to be enzymatically active in Type III CRISPR-Cas systems but inactivated in Type I systems. These findings, the fact that the CRISPR polymerases, RAMPs and Cas2 all contain core RRM domains, and distinct gene arrangements in the three types of CRISPR-Cas systems together provide for a simple scenario for origin and evolution of the CRISPR-Cas machinery. Under this scenario, the CRISPR-Cas system originated in thermophilic Archaea and subsequently spread horizontally among prokaryotes.</p> <p>Conclusions</p> <p>Because of the extreme diversity of CRISPR-Cas systems, in-depth sequence and structure comparison continue to reveal unexpected homologous relationship among Cas proteins. Unification of Cas protein families previously considered unrelated provides for improvement in the classification of CRISPR-Cas systems and a reconstruction of their evolution.</p> <p>Open peer review</p> <p>This article was reviewed by Malcolm White (nominated by Purficacion Lopez-Garcia), Frank Eisenhaber and Igor Zhulin. For the full reviews, see the Reviewers' Comments section.</p>
first_indexed 2024-04-13T11:43:21Z
format Article
id doaj.art-ee0e5ba8e3ac49cdbae2a46d4be919bd
institution Directory Open Access Journal
issn 1745-6150
language English
last_indexed 2024-04-13T11:43:21Z
publishDate 2011-07-01
publisher BMC
record_format Article
series Biology Direct
spelling doaj.art-ee0e5ba8e3ac49cdbae2a46d4be919bd2022-12-22T02:48:15ZengBMCBiology Direct1745-61502011-07-01613810.1186/1745-6150-6-38Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systemsWolf Yuri IAravind LMakarova Kira SKoonin Eugene V<p>Abstract</p> <p>Background</p> <p>The CRISPR-Cas adaptive immunity systems that are present in most Archaea and many Bacteria function by incorporating fragments of alien genomes into specific genomic loci, transcribing the inserts and using the transcripts as guide RNAs to destroy the genome of the cognate virus or plasmid. This RNA interference-like immune response is mediated by numerous, diverse and rapidly evolving Cas (CRISPR-associated) proteins, several of which form the Cascade complex involved in the processing of CRISPR transcripts and cleavage of the target DNA. Comparative analysis of the Cas protein sequences and structures led to the classification of the CRISPR-Cas systems into three Types (I, II and III).</p> <p>Results</p> <p>A detailed comparison of the available sequences and structures of Cas proteins revealed several unnoticed homologous relationships. The Repeat-Associated Mysterious Proteins (RAMPs) containing a distinct form of the RNA Recognition Motif (RRM) domain, which are major components of the CRISPR-Cas systems, were classified into three large groups, Cas5, Cas6 and Cas7. Each of these groups includes many previously uncharacterized proteins now shown to adopt the RAMP structure. Evidence is presented that large subunits contained in most of the CRISPR-Cas systems could be homologous to Cas10 proteins which contain a polymerase-like Palm domain and are predicted to be enzymatically active in Type III CRISPR-Cas systems but inactivated in Type I systems. These findings, the fact that the CRISPR polymerases, RAMPs and Cas2 all contain core RRM domains, and distinct gene arrangements in the three types of CRISPR-Cas systems together provide for a simple scenario for origin and evolution of the CRISPR-Cas machinery. Under this scenario, the CRISPR-Cas system originated in thermophilic Archaea and subsequently spread horizontally among prokaryotes.</p> <p>Conclusions</p> <p>Because of the extreme diversity of CRISPR-Cas systems, in-depth sequence and structure comparison continue to reveal unexpected homologous relationship among Cas proteins. Unification of Cas protein families previously considered unrelated provides for improvement in the classification of CRISPR-Cas systems and a reconstruction of their evolution.</p> <p>Open peer review</p> <p>This article was reviewed by Malcolm White (nominated by Purficacion Lopez-Garcia), Frank Eisenhaber and Igor Zhulin. For the full reviews, see the Reviewers' Comments section.</p>http://www.biology-direct.com/content/6/1/38
spellingShingle Wolf Yuri I
Aravind L
Makarova Kira S
Koonin Eugene V
Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems
Biology Direct
title Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems
title_full Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems
title_fullStr Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems
title_full_unstemmed Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems
title_short Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems
title_sort unification of cas protein families and a simple scenario for the origin and evolution of crispr cas systems
url http://www.biology-direct.com/content/6/1/38
work_keys_str_mv AT wolfyurii unificationofcasproteinfamiliesandasimplescenariofortheoriginandevolutionofcrisprcassystems
AT aravindl unificationofcasproteinfamiliesandasimplescenariofortheoriginandevolutionofcrisprcassystems
AT makarovakiras unificationofcasproteinfamiliesandasimplescenariofortheoriginandevolutionofcrisprcassystems
AT koonineugenev unificationofcasproteinfamiliesandasimplescenariofortheoriginandevolutionofcrisprcassystems