The CRISPR Spacer Space Is Dominated by Sequences from Species-Specific Mobilomes

ABSTRACT Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein (CRISPR-Cas) systems store the memory of past encounters with foreign DNA in unique spacers that are inserted between direct repeats in CRISPR arrays. For only a small fraction of the spacers, homologous...

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Autores principales:	Sergey A. Shmakov, Vassilii Sitnik, Kira S. Makarova, Yuri I. Wolf, Konstantin V. Severinov, Eugene V. Koonin
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	CRISPR-Cas bacteriophages mobilome oligonucleotide composition spacer acquisition Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8c876cbf1aa040bc86fed2699abe75c8
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spelling	oai:doaj.org-article:8c876cbf1aa040bc86fed2699abe75c82021-11-15T15:51:51ZThe CRISPR Spacer Space Is Dominated by Sequences from Species-Specific Mobilomes10.1128/mBio.01397-172150-7511https://doaj.org/article/8c876cbf1aa040bc86fed2699abe75c82017-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01397-17https://doaj.org/toc/2150-7511ABSTRACT Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein (CRISPR-Cas) systems store the memory of past encounters with foreign DNA in unique spacers that are inserted between direct repeats in CRISPR arrays. For only a small fraction of the spacers, homologous sequences, called protospacers, are detectable in viral, plasmid, and microbial genomes. The rest of the spacers remain the CRISPR “dark matter.” We performed a comprehensive analysis of the spacers from all CRISPR-cas loci identified in bacterial and archaeal genomes, and we found that, depending on the CRISPR-Cas subtype and the prokaryotic phylum, protospacers were detectable for 1% to about 19% of the spacers (~7% global average). Among the detected protospacers, the majority, typically 80 to 90%, originated from viral genomes, including proviruses, and among the rest, the most common source was genes that are integrated into microbial chromosomes but are involved in plasmid conjugation or replication. Thus, almost all spacers with identifiable protospacers target mobile genetic elements (MGE). The GC content, as well as dinucleotide and tetranucleotide compositions, of microbial genomes, their spacer complements, and the cognate viral genomes showed a nearly perfect correlation and were almost identical. Given the near absence of self-targeting spacers, these findings are most compatible with the possibility that the spacers, including the dark matter, are derived almost completely from the species-specific microbial mobilomes. IMPORTANCE The principal function of CRISPR-Cas systems is thought to be protection of bacteria and archaea against viruses and other parasitic genetic elements. The CRISPR defense function is mediated by sequences from parasitic elements, known as spacers, that are inserted into CRISPR arrays and then transcribed and employed as guides to identify and inactivate the cognate parasitic genomes. However, only a small fraction of the CRISPR spacers match any sequences in the current databases, and of these, only a minority correspond to known parasitic elements. We show that nearly all spacers with matches originate from viral or plasmid genomes that are either free or have been integrated into the host genome. We further demonstrate that spacers with no matches have the same properties as those of identifiable origins, strongly suggesting that all spacers originate from mobile elements.Sergey A. ShmakovVassilii SitnikKira S. MakarovaYuri I. WolfKonstantin V. SeverinovEugene V. KooninAmerican Society for MicrobiologyarticleCRISPR-Casbacteriophagesmobilomeoligonucleotide compositionspacer acquisitionMicrobiologyQR1-502ENmBio, Vol 8, Iss 5 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	CRISPR-Cas bacteriophages mobilome oligonucleotide composition spacer acquisition Microbiology QR1-502
spellingShingle	CRISPR-Cas bacteriophages mobilome oligonucleotide composition spacer acquisition Microbiology QR1-502 Sergey A. Shmakov Vassilii Sitnik Kira S. Makarova Yuri I. Wolf Konstantin V. Severinov Eugene V. Koonin The CRISPR Spacer Space Is Dominated by Sequences from Species-Specific Mobilomes
description	ABSTRACT Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein (CRISPR-Cas) systems store the memory of past encounters with foreign DNA in unique spacers that are inserted between direct repeats in CRISPR arrays. For only a small fraction of the spacers, homologous sequences, called protospacers, are detectable in viral, plasmid, and microbial genomes. The rest of the spacers remain the CRISPR “dark matter.” We performed a comprehensive analysis of the spacers from all CRISPR-cas loci identified in bacterial and archaeal genomes, and we found that, depending on the CRISPR-Cas subtype and the prokaryotic phylum, protospacers were detectable for 1% to about 19% of the spacers (~7% global average). Among the detected protospacers, the majority, typically 80 to 90%, originated from viral genomes, including proviruses, and among the rest, the most common source was genes that are integrated into microbial chromosomes but are involved in plasmid conjugation or replication. Thus, almost all spacers with identifiable protospacers target mobile genetic elements (MGE). The GC content, as well as dinucleotide and tetranucleotide compositions, of microbial genomes, their spacer complements, and the cognate viral genomes showed a nearly perfect correlation and were almost identical. Given the near absence of self-targeting spacers, these findings are most compatible with the possibility that the spacers, including the dark matter, are derived almost completely from the species-specific microbial mobilomes. IMPORTANCE The principal function of CRISPR-Cas systems is thought to be protection of bacteria and archaea against viruses and other parasitic genetic elements. The CRISPR defense function is mediated by sequences from parasitic elements, known as spacers, that are inserted into CRISPR arrays and then transcribed and employed as guides to identify and inactivate the cognate parasitic genomes. However, only a small fraction of the CRISPR spacers match any sequences in the current databases, and of these, only a minority correspond to known parasitic elements. We show that nearly all spacers with matches originate from viral or plasmid genomes that are either free or have been integrated into the host genome. We further demonstrate that spacers with no matches have the same properties as those of identifiable origins, strongly suggesting that all spacers originate from mobile elements.
format	article
author	Sergey A. Shmakov Vassilii Sitnik Kira S. Makarova Yuri I. Wolf Konstantin V. Severinov Eugene V. Koonin
author_facet	Sergey A. Shmakov Vassilii Sitnik Kira S. Makarova Yuri I. Wolf Konstantin V. Severinov Eugene V. Koonin
author_sort	Sergey A. Shmakov
title	The CRISPR Spacer Space Is Dominated by Sequences from Species-Specific Mobilomes
title_short	The CRISPR Spacer Space Is Dominated by Sequences from Species-Specific Mobilomes
title_full	The CRISPR Spacer Space Is Dominated by Sequences from Species-Specific Mobilomes
title_fullStr	The CRISPR Spacer Space Is Dominated by Sequences from Species-Specific Mobilomes
title_full_unstemmed	The CRISPR Spacer Space Is Dominated by Sequences from Species-Specific Mobilomes
title_sort	crispr spacer space is dominated by sequences from species-specific mobilomes
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/8c876cbf1aa040bc86fed2699abe75c8
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The CRISPR Spacer Space Is Dominated by Sequences from Species-Specific Mobilomes

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