Arms races between mobile genetic elements and prokaryotic hosts are major drivers of ecological and evolutionary change in microbial communities. Prokaryotic defense systems such as CRISPR-Cas have the potential to regulate microbiome composition by modifying the interactions among bacteria, plasmids, and phages. Here, we used longitudinal metagenomic data from 130 healthy and diseased individuals to study how the interplay of genetic parasites and CRISPR-Cas immunity reflects on the dynamics and composition of the human gut microbiome. Based on the coordinated study of 80 000 CRISPR-Cas loci and their targets, we show that CRISPR-Cas immunity effectively modulates bacteriophage abundances in the gut. Acquisition of CRISPR-Cas immunity typically leads to a decrease in the abundance of lytic phages but does not necessarily cause their complete disappearance. Much smaller effects are observed for lysogenic phages and plasmids. Conversely, phage-CRISPR interactions shape bacterial microdiversity by producing weak selective sweeps that benefit immune host lineages. We also show that distal (and chronologically older) regions of CRISPR arrays are enriched in spacers that are potentially functional and target crass-like phages and local prophages. This suggests that exposure to reactivated prophages and other endemic viruses is a major selective pressure in the gut microbiome that drives the maintenance of long-lasting immune memory.

中文翻译：

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人类肠道微生物组中 CRISPR 介导的病毒与宿主相互作用的动态


移动遗传元件和原核宿主之间的军备竞赛是微生物群落生态和进化变化的主要驱动力。 CRISPR-Cas 等原核防御系统具有通过改变细菌、质粒和噬菌体之间的相互作用来调节微生物组组成的潜力。在这里，我们使用来自 130 名健康和患病个体的纵向宏基因组数据来研究遗传寄生虫和 CRISPR-Cas 免疫的相互作用如何影响人类肠道微生物组的动态和组成。基于对 80 000 个 CRISPR-Cas 位点及其靶标的协调研究，我们表明 CRISPR-Cas 免疫可有效调节肠道中的噬菌体丰度。获得 CRISPR-Cas 免疫力通常会导致裂解噬菌体丰度减少，但并不一定会导致其完全消失。对于溶原性噬菌体和质粒观察到的影响要小得多。相反，噬菌体-CRISPR 相互作用通过产生有利于免疫宿主谱系的弱选择性扫描来塑造细菌微多样性。我们还表明，CRISPR 阵列的远端（并且按时间顺序排列较旧）区域富含间隔区，这些间隔区具有潜在的功能并针对粗类噬菌体和局部原噬菌体。这表明，接触重新激活的原噬菌体和其他地方性病毒是肠道微生物群中的主要选择压力，可促进长期免疫记忆的维持。