A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes.

A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes.
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DOI:
10.1371/journal.pcbi.0010060
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发表时间:
2005-11
影响因子:
4.3
通讯作者:
Nelson KE
Nelson KE
中科院分区:
生物学2区
文献类型:
--
作者:
Haft DH;Selengut J;Mongodin EF;Nelson KE

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聚集规律间隔短回文重复序列(crispr)是在许多原核生物基因组中发现的DNA直接重复序列家族。21 - 37bp的重复序列通常表现出弱的双体对称性,并被规则大小的非重复间隔序列分开。四个CRISPR相关(Cas)蛋白家族,被称为Cas1至Cas4,与CRISPR元件严格相关,并且总是发生在重复簇附近。一些间隔序列源自可移动的遗传元素,被认为对含有这些序列的元素具有“免疫力”。在本研究中,我们系统地研究了在这些CRISPR位点附近编码的未鉴定的蛋白质,并发现了许多与多个原核生物物种的CRISPR位点严格相关的其他蛋白质家族。建立了45个Cas蛋白家族的多序列比对和隐马尔可夫模型。这些模型具有很高的灵敏度和选择性,并将黄粘球菌发育的关键调控因子DevR和DevS分类为Cas蛋白。这些鉴定表明,CRISPR/cas基因区域可以相当大,多达20个不同的、串联排列的cas基因靠近一个重复簇或填充两个重复簇之间的区域。Cas蛋白集合的独特亚群在系统发育上遥远的物种中反复出现,并与特征重复周期相关。本文提出的分析支持了这些单位的移动性的初步建议,以及不同亚型的基因座相互作用以及与宿主细胞防御、复制和调节系统相互作用的可能性。从这一分析中可以明显看出,CRISPR/cas基因座比以前认为的更大、更复杂、更异质。集群规则间隔短回文重复序列(crispr)家族描述了在近一半的细菌和古细菌基因组中发现的一类DNA重复序列。这些DNA重复区域具有非常规则的结构:位于每对重复序列之间的独特的恒定大小的序列,称为间隔。DNA重复序列不编码蛋白质,但似乎被转录并加工成可能具有多种功能的小rna,包括抵抗序列与间隔序列匹配的任何噬菌体(即病毒或细菌);随着微生物菌株的进化,间隔物会迅速变化。这项工作描述了41个新的crispr相关(cas)基因家族,除了之前已知的4个外,它们总是在这些重复序列附近发现。这表明CRISPR系统属于不同的类别,具有不同的重复模式,不同的基因集和物种范围。它们中的大多数似乎在宿主基因组中来去迅速。这些可能有益的移动遗传元件可能在推动原核生物进化中发挥重要作用。
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. The family of clustered regularly interspaced short palindromic repeats (CRISPRs) describes a class of DNA repeats found in nearly half of all bacterial and archaeal genomes. These DNA repeat regions have a remarkably regular structure: unique sequences of constant size, called spacers, sit between each pair of repeats. The DNA repeats do not encode proteins, but appear to be transcribed and processed into small RNAs that may have any number of functions, including resistance to any phage (i.e., virus of bacteria) whose sequence matches a spacer; spacers change rapidly as microbial strains evolve. This work describes 41 new CRISPR-associated (cas) gene families, which are always found near these repeats, in addition to the four previously known. It shows that CRISPR systems belong to different classes, with different repeat patterns, sets of genes, and species ranges. Most of these seem to come and go rather rapidly from their host genomes. These possibly beneficial mobile genetic elements may play an important role in driving prokaryotic evolution.
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发表时间: 2005-03-01
期刊: MICROBIOLOGY-SGM
影响因子: 2.8
作者:
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影响因子: 3.2
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影响因子: 3.9
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发表时间: 1997-04-01
影响因子: 9.4
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DOI: 10.1128/jb.185.8.2410-2417.2003
发表时间: 2003-04-01
影响因子: 3.2
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