Unexpected evolutionary benefit to phages imparted by bacterial CRISPR-Cas9.

Unexpected evolutionary benefit to phages imparted by bacterial CRISPR-Cas9.
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DOI:
10.1126/sciadv.aar4134
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发表时间:
2018-03
期刊:
影响因子:
13.6
通讯作者:
Rao V
Rao V
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Tao P;Wu X;Rao V

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噬菌体在被细菌CRISPR/Cas系统攻击时显示出升高的突变率和显著快速的进化。细菌和噬菌体用各种防御和反防御机制武装自己,以保护自己的基因组并降解其他基因组。CRISPR(clustered regularly interspaced short palindromic repeat)-Cas(CRISPR相关)是一种适应性细菌防御机制,它识别入侵噬菌体基因组的短片段,并通过核酸酶攻击将其破坏。出乎意料的是,我们发现CRISPR-Cas系统也可能加速噬菌体进化。当含有CRISPR-Cas9的大肠杆菌细菌被噬菌体T4感染时,其胞嘧啶羟甲基化和葡萄糖基化的基因组被Cas9核酸酶切割得很差,但持续的CRISPR-Cas9压力导致突变体的快速进化,甚至在形成单个噬菌斑时也会积累。值得注意的是,突变频率比没有CRISPR压力的自发突变频率高出约6个数量级。我们的研究结果导致了一种假设,即CRISPR-Cas可能是一把双刃剑,为细菌和细菌提供生存优势,导致它们在地球上共同进化和丰富。
Phages show an elevated mutation rate and remarkably rapid evolution when attacked by the bacterial CRISPR/Cas system. Bacteria and bacteriophages arm themselves with various defensive and counterdefensive mechanisms to protect their own genome and degrade the other’s. CRISPR (clustered regularly interspaced short palindromic repeat)–Cas (CRISPR-associated) is an adaptive bacterial defense mechanism that recognizes short stretches of invading phage genome and destroys it by nuclease attack. Unexpectedly, we discovered that the CRISPR-Cas system might also accelerate phage evolution. When Escherichia coli bacteria containing CRISPR-Cas9 were infected with phage T4, its cytosine hydroxymethylated and glucosylated genome was cleaved poorly by Cas9 nuclease, but the continuing CRISPR-Cas9 pressure led to rapid evolution of mutants that accumulated even by the time a single plaque was formed. The mutation frequencies are, remarkably, approximately six orders of magnitude higher than the spontaneous mutation frequency in the absence of CRISPR pressure. Our findings lead to the hypothesis that the CRISPR-Cas might be a double-edged sword, providing survival advantages to both bacteria and phages, leading to their coevolution and abundance on Earth.
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