A chimeric nuclease substitutes a phage CRISPR-Cas system to provide sequence-specific immunity against subviral parasites.
A chimeric nuclease substitutes a phage CRISPR-Cas system to provide sequence-specific immunity against subviral parasites.
复制标题
嵌合核酸酶取代噬菌体CRISPR-Cas系统以提供针对亚病毒寄生虫的序列特异性免疫。
DOI：
10.7554/elife.68339
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发表时间：
2021-07-07
期刊：
影响因子：
7.7
通讯作者：
Seed KD
中科院分区：
文献类型：
--
作者：
Barth ZK;Nguyen MH;Seed KD
可移动的遗传元素，可以在基因组之间水平移动的元素，对宿主的适应性有深远的影响。噬菌体诱导染色体岛样元件（PLE）是一种可移动元件，它整合到霍乱弧菌的染色体上，寄生在噬菌体ICP1上，在细胞间移动。这种寄生是这样的，它消除了ICP1后代的产生，并为宿主细胞群体提供了防御性的福利。为了应对PLE的严重寄生，ICP1获得了一种自适应CRISPR-Cas系统，该系统在感染期间靶向PLE基因组。然而，天然缺乏CRISPR-Cas的ICP1分离株仍然能够克服某些PLE变异体，并且这种针对PLE的免疫机制迄今仍不清楚。在这里，我们发现缺乏CRISPR-Cas的ICP1分离株在相同的位点上编码一个内切酶，并且该内切酶使ICP1对一部分ple具有免疫力。进一步分析表明，该内切酶具有嵌合起源，其dna结合结构域与一些PLE复制起源结合蛋白高度相似。这种相似性使得核酸内切酶能够结合和切割PLE的复制起点。核酸内切酶似乎对PLE施加了相当大的选择压力，并可能驱动PLE复制模块交换和起源重组作为逃逸机制。这项工作表明，新的基因组防御系统可以通过结构域洗牌产生，并提供了对驱动基因组模块化和移动元件时间演替的进化力量的更好理解。
Mobile genetic elements, elements that can move horizontally between genomes, have profound effects on their host's fitness. The phage-inducible chromosomal island-like element (PLE) is a mobile element that integrates into the chromosome of Vibrio cholerae and parasitizes the bacteriophage ICP1 to move between cells. This parasitism by PLE is such that it abolishes the production of ICP1 progeny and provides a defensive boon to the host cell population. In response to the severe parasitism imposed by PLE, ICP1 has acquired an adaptive CRISPR-Cas system that targets the PLE genome during infection. However, ICP1 isolates that naturally lack CRISPR-Cas are still able to overcome certain PLE variants, and the mechanism of this immunity against PLE has thus far remained unknown. Here, we show that ICP1 isolates that lack CRISPR-Cas encode an endonuclease in the same locus, and that the endonuclease provides ICP1 with immunity to a subset of PLEs. Further analysis shows that this endonuclease is of chimeric origin, incorporating a DNA-binding domain that is highly similar to some PLE replication origin-binding proteins. This similarity allows the endonuclease to bind and cleave PLE origins of replication. The endonuclease appears to exert considerable selective pressure on PLEs and may drive PLE replication module swapping and origin restructuring as mechanisms of escape. This work demonstrates that new genome defense systems can arise through domain shuffling and provides a greater understanding of the evolutionary forces driving genome modularity and temporal succession in mobile elements.
影响因子：
14.9
作者：
Liu Q;Derbyshire V;Belfort M;Edgell DR
通讯作者：
Edgell DR
影响因子：
14.9
作者：
Roy AC;Wilson GG;Edgell DR
通讯作者：
Edgell DR