Comprehensive comparative-genomic analysis of type 2 toxin-antitoxin systems and related mobile stress response systems in prokaryotes.
Comprehensive comparative-genomic analysis of type 2 toxin-antitoxin systems and related mobile stress response systems in prokaryotes.
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DOI：
10.1186/1745-6150-4-19
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发表时间：
2009-06-03
期刊：
影响因子：
5.5
通讯作者：
Koonin EV
中科院分区：
文献类型：
--
作者：
Makarova KS;Wolf YI;Koonin EV
原核生物毒素-抗毒素系统(TAS，又称TA基因座)是广泛存在的、可移动的双基因模块，可被视为自私的遗传元件，因为它们进化出对复制子和它们所在的细胞上瘾的机制，但在各种形式的应激反应和原核生物种群的管理中也具有“正常”的细胞功能。几种不同的1型TA，其中毒素是一种蛋白质，抗毒素是反义RNA，以及许多不相关的2型TA，其中毒素和抗毒素都是蛋白质，已经被实验表征，并怀疑还有更多的TA有待识别。我们报道了原核生物中2型毒素-抗毒素系统的全面比较基因组分析。利用敏感的远距离序列相似性搜索方法、基因组上下文分析和一种新的鉴定移动双组分系统的方法，我们鉴定了许多以前未被注意到的蛋白质家族，它们与已知的2型TAS毒素和抗毒素同源。此外，我们预测了12个新的毒素家族和13个抗毒素家族，并预测了几个以前没有被怀疑具有这种功能的基因模块的TAS或TAS样活性。特别是，我们提出的迹象表明，编码最小核苷酸转移酶和伴随的HEPN蛋白的双基因模块，在许多古生菌和细菌中极其丰富，特别是嗜热菌可能包含一种新的TAS。我们对古菌和细菌的750个完整基因组中的已知和新预测的TAS进行了调查，定量地证明了TAS的非凡流动性，并探索了结合可塑性和选择性的毒素-抗毒素配对网络。TAS的特有特性，即毒素和抗毒素基因的典型小尺寸、快速进化和广泛的水平流动性，使得全面鉴定这些系统的任务特别具有挑战性。然而，这些相同的性质可以被用来开发基于上下文的计算方法，在这项工作中，结合对细微序列相似性的详尽分析，通过预测以前未被注意到的已知毒素和抗毒素的衍生版本，以及假定的新型TAS类系统，大大扩展了目前的TAS集合。在更广泛的背景下，TAS属于原核生物运动组的抗性结构域，它包括部分自私的、成瘾的基因盒，参与胁迫反应的各个方面，并与TAS在相同的一般原则下组织。TAS类系统的“自私利他主义”或“负责任的自私”似乎是抵抗组的一个决定性特征，也是整个原核泛基因组的一个重要特征，因为在原核生物世界中，移动体和“稳定的”染色体形成了一个动态的连续体。本文由Kenn Gerdes(由Arcady Mushegean提名)、Daniel Haft、Arcady Mushegean和Andrei Osterman审阅。要获得完整的评论，请转到评论者报告部分。
The prokaryotic toxin-antitoxin systems (TAS, also referred to as TA loci) are widespread, mobile two-gene modules that can be viewed as selfish genetic elements because they evolved mechanisms to become addictive for replicons and cells in which they reside, but also possess "normal" cellular functions in various forms of stress response and management of prokaryotic population. Several distinct TAS of type 1, where the toxin is a protein and the antitoxin is an antisense RNA, and numerous, unrelated TAS of type 2, in which both the toxin and the antitoxin are proteins, have been experimentally characterized, and it is suspected that many more remain to be identified. We report a comprehensive comparative-genomic analysis of Type 2 toxin-antitoxin systems in prokaryotes. Using sensitive methods for distant sequence similarity search, genome context analysis and a new approach for the identification of mobile two-component systems, we identified numerous, previously unnoticed protein families that are homologous to toxins and antitoxins of known type 2 TAS. In addition, we predict 12 new families of toxins and 13 families of antitoxins, and also, predict a TAS or TAS-like activity for several gene modules that were not previously suspected to function in that capacity. In particular, we present indications that the two-gene module that encodes a minimal nucleotidyl transferase and the accompanying HEPN protein, and is extremely abundant in many archaea and bacteria, especially, thermophiles might comprise a novel TAS. We present a survey of previously known and newly predicted TAS in 750 complete genomes of archaea and bacteria, quantitatively demonstrate the exceptional mobility of the TAS, and explore the network of toxin-antitoxin pairings that combines plasticity with selectivity. The defining properties of the TAS, namely, the typically small size of the toxin and antitoxin genes, fast evolution, and extensive horizontal mobility, make the task of comprehensive identification of these systems particularly challenging. However, these same properties can be exploited to develop context-based computational approaches which, combined with exhaustive analysis of subtle sequence similarities were employed in this work to substantially expand the current collection of TAS by predicting both previously unnoticed, derived versions of known toxins and antitoxins, and putative novel TAS-like systems. In a broader context, the TAS belong to the resistome domain of the prokaryotic mobilome which includes partially selfish, addictive gene cassettes involved in various aspects of stress response and organized under the same general principles as the TAS. The "selfish altruism", or "responsible selfishness", of TAS-like systems appears to be a defining feature of the resistome and an important characteristic of the entire prokaryotic pan-genome given that in the prokaryotic world the mobilome and the "stable" chromosomes form a dynamic continuum. This paper was reviewed by Kenn Gerdes (nominated by Arcady Mushegian), Daniel Haft, Arcady Mushegian, and Andrei Osterman. For full reviews, go to the Reviewers' Reports section.
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影响因子：
4.4
作者：
Feder M;Bujnicki JM
通讯作者：
Bujnicki JM
影响因子：
3.2
作者：
Barrios, AFG;Zuo, RJ;Wood, TK
通讯作者：
Wood, TK
DOI：
10.1107/s1744309105012376
发表时间：
2005-05-01
影响因子：
0.9
作者：
Cameron, S;McLuskey, K;Hunter, WN
通讯作者：
Hunter, WN
DOI：
10.1073/pnas.0808832106
发表时间：
2009-01-20
影响因子：
11.1
作者：
Fineran, Peter C.;Blower, Tim R.;Salmond, George P. C.
通讯作者：
Salmond, George P. C.
DOI：
10.1099/00221287-143-2-553
发表时间：
1997-02-01
期刊：
MICROBIOLOGY-UK
影响因子：
--
作者：
Bloomfield, GA;Whittle, G;Cheetham, BF
通讯作者：
Cheetham, BF