Nasty viruses, costly plasmids, population dynamics, and the conditions for establishing and maintaining CRISPR-mediated adaptive immunity in bacteria.
Nasty viruses, costly plasmids, population dynamics, and the conditions for establishing and maintaining CRISPR-mediated adaptive immunity in bacteria.
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DOI：
10.1371/journal.pgen.1001171
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发表时间：
2010-10-28
期刊：
影响因子：
4.5
通讯作者：
Levin BR
中科院分区：
文献类型：
--
作者：
Levin BR
聚集的、规则间隔的短回文重复序列（CRISPR）在几乎所有的古细菌和近一半的真细菌的基因组中大量存在。通过遗传干扰机制，具有CRISPR区域的细菌携带先前遇到的噬菌体和质粒的DNA拷贝，从而终止具有这些序列的噬菌体和质粒的复制。因此，防止噬菌体和质粒感染似乎是在细菌种群中建立和维持CRISPR的选择压力。但这是真的吗？为了解决这个问题，并为CRISPR的生态学和进化的实验研究提供一个框架和假设，我使用了带有裂解噬菌体和共轭质粒的CRISPR编码细菌种群动力学的数学模型。这些模型的参数在大肠杆菌及其噬菌体和共轭质粒的估计范围内，对这些模型的特性进行数值（计算机模拟）分析的结果表明：(1)在裂解噬菌体存在的情况下，具有crispr介导免疫的细菌在与具有更高马尔萨斯适应度的非crispr细菌竞争时具有优势。(2)当存在对噬菌体的包膜抗性时，CRISPR存在的条件更窄。(3)虽然在某些情况下，CRISPR介导的免疫可以使细菌在与携带有害共轭质粒的马尔萨斯适应度较高的细菌竞争时获得优势，但获得这种优势的条件相对狭窄，有利于CRISPR的选择强度较弱。这些模型的参数可以独立估计，其构建背后的假设得到验证，并且通过对其特性的分析产生的假设在具有裂解噬菌体和共轭质粒的实验细菌群体中进行了测试。我提出了估计这些参数的协议，并概述了实验设计，以评估这些模型的有效性并检验这些假设。CRISPR是适应性免疫系统的缩写，在几乎所有的古细菌和近一半的真细菌中都发现了这种系统。与细菌对噬菌体和其他有害dna的其他防御不同，CRISPR具有特异性、记忆性和终止具有几乎无限多样性的有害dna感染的能力。在本报告中，利用细菌、噬菌体和质粒群体动力学的数学模型来确定CRISPR在细菌群体中建立和维持的条件，以及这种适应性免疫系统对细菌和噬菌体的生态和（共同）进化的贡献。这些模型预测了现实和广泛的条件，在这种条件下，携带CRISPR区域的细菌可以在面对噬菌体的高适应度细菌群体中入侵并维持下去，而在与携带共轭质粒的竞争对手对抗时，这种条件更窄。这些模型预测，CRISPR可以促进噬菌体和细菌之间以及噬菌体-而不是资源有限的细菌群落之间的长期共同进化军备竞赛。这些模型的参数可以独立估计，其构建背后的假设可以得到验证，并且通过对其特性的分析产生的假设可以用实验细菌群体进行测试。
Clustered, Regularly Interspaced Short Palindromic Repeats (CRISPR) abound in the genomes of almost all archaebacteria and nearly half the eubacteria sequenced. Through a genetic interference mechanism, bacteria with CRISPR regions carrying copies of the DNA of previously encountered phage and plasmids abort the replication of phage and plasmids with these sequences. Thus it would seem that protection against infecting phage and plasmids is the selection pressure responsible for establishing and maintaining CRISPR in bacterial populations. But is it? To address this question and provide a framework and hypotheses for the experimental study of the ecology and evolution of CRISPR, I use mathematical models of the population dynamics of CRISPR-encoding bacteria with lytic phage and conjugative plasmids. The results of the numerical (computer simulation) analysis of the properties of these models with parameters in the ranges estimated for Escherichia coli and its phage and conjugative plasmids indicate: (1) In the presence of lytic phage there are broad conditions where bacteria with CRISPR-mediated immunity will have an advantage in competition with non-CRISPR bacteria with otherwise higher Malthusian fitness. (2) These conditions for the existence of CRISPR are narrower when there is envelope resistance to the phage. (3) While there are situations where CRISPR-mediated immunity can provide bacteria an advantage in competition with higher Malthusian fitness bacteria bearing deleterious conjugative plasmids, the conditions for this to obtain are relatively narrow and the intensity of selection favoring CRISPR weak. The parameters of these models can be independently estimated, the assumption behind their construction validated, and the hypotheses generated from the analysis of their properties tested in experimental populations of bacteria with lytic phage and conjugative plasmids. I suggest protocols for estimating these parameters and outline the design of experiments to evaluate the validity of these models and test these hypotheses. CRISPR is the acronym for the adaptive immune system that has been found in almost all archaebacteria and nearly half the eubacteria examined. Unlike the other defenses bacteria have for protection from phage and other deleterious DNAs, CRISPR has the virtues of specificity, memory, and the capacity to abort infections with a virtually indefinite diversity of deleterious DNAs. In this report, mathematical models of the population dynamics of bacteria, phage, and plasmids are used to determine the conditions under which CRISPR can become established and will be maintained in bacterial populations and the contribution of this adaptive immune system to the ecology and (co)evolution of bacteria and bacteriophage. The models predict realistic and broad conditions under which bacteria bearing CRISPR regions can invade and be maintained in populations of higher fitness bacteria confronted with bacteriophage and narrower conditions when the confrontation is with competitors carrying conjugative plasmids. The models predict that CRISPR can facilitate long-term co-evolutionary arms races between phage and bacteria and between phage- rather than resource-limited bacterial communities. The parameters of these models can be independently estimated, the assumptions behind their construction validated, and the hypotheses generated from the analysis of their properties tested with experimental populations of bacteria.
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影响因子：
64.8
作者：
Forde, Samantha E.;Beardmore, Robert E.;Hurst, Laurence D.
通讯作者：
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DOI：
10.1073/pnas.0600166103
发表时间：
2006-03-21
影响因子：
11.1
作者：
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影响因子：
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影响因子：
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作者：
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