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Abstract：
Prokaryotic type I CRISPR-Cas systems respond to the presence of mobile genetic elements such as plasmids and phages in two different ways. CRISPR interference efficiently destroys foreign DNA harboring protospacers fully matching CRISPR RNA spacers. In contrast, even a single mismatch between a spacer and a protospacer can render CRISPR interference ineffective but causes primed adaptation-efficient and specific acquisition of additional spacers from foreign DNA into the CRISPR array of the host. It has been proposed that the interference and primed adaptation pathways are mediated by structurally different complexes formed by the effector Cascade complex on matching and mismatched protospacers. Here, we present experimental evidence and present a simple mathematical model that shows that when plasmid copy number maintenance/phage genome replication is taken into account, the two apparently different outcomes of the CRISPR-Cas response can be accounted for by just one kind of effector complex on both targets. The results underscore the importance of consideration of targeted genome biology when considering consequences of CRISPR-Cas systems action.
摘要：
原核I型CRISPR-Cas系统以两种不同的方式响应可移动遗传元件如质粒和噬菌体的存在。CRISPR干扰有效地破坏具有完全匹配CRISPRRNA间隔区的原型间隔区的外源DNA。相比之下,即使间隔区和前间隔区之间的单个错配也会使CRISPR干扰无效,但会导致启动的适应效率和特异性地从外源DNA获得额外的间隔区进入宿主的CRISPR阵列.已经提出，干扰和引发的适应途径是由匹配和错配的原型间隔区上的效应子Cascade复合物形成的结构不同的复合物介导的。这里,我们提供了实验证据，并提出了一个简单的数学模型，表明当考虑到质粒拷贝数维持/噬菌体基因组复制时，CRISPR-Cas反应的两种明显不同的结果可以由两种靶标上的一种效应复合物来解释。结果强调了在考虑CRISPR-Cas系统作用的后果时考虑靶向基因组生物学的重要性。
