The CRISPR-Cas systems of bacterial and archaeal adaptive immunity have become a household name among biologists and even the general public thanks to the unprecedented success of the new generation of genome editing tools utilizing Cas proteins. However, the fundamental biological features of CRISPR-Cas are of no lesser interest and have major impacts on our understanding of the evolution of antivirus defense, host-parasite coevolution, self versus non-self discrimination and mechanisms of adaptation. CRISPR-Cas systems present the best known case in point for Lamarckian evolution, i.e. generation of heritable, adaptive genomic changes in response to encounters with external factors, in this case, foreign nucleic acids. CRISPR-Cas systems employ multiple mechanisms of self versus non-self discrimination but, as is the case with immune systems in general, are nevertheless costly because autoimmunity cannot be eliminated completely. In addition to the autoimmunity, the fitness cost of CRISPR-Cas systems appears to be determined by their inhibitory effect on horizontal gene transfer, curtailing evolutionary innovation. Hence the dynamic evolution of CRISPR-Cas loci that are frequently lost and (re)acquired by archaea and bacteria. Another fundamental biological feature of CRISPR-Cas is its intimate connection with programmed cell death and dormancy induction in microbes. In this and, possibly, other immune systems, active immune response appears to be coupled to a different form of defense, namely, “altruistic” shutdown of cellular functions resulting in protection of neighboring cells. Finally, analysis of the evolutionary connections of Cas proteins reveals multiple contributions of mobile genetic elements (MGE) to the origin of various components of CRISPR-Cas systems, furthermore, different biological systems that function by genome manipulation appear to have evolved convergently from unrelated MGE. The shared features of adaptive defense systems and MGE, namely the ability to recognize and cleave unique sites in genomes, make them ideal candidates for genome editing and engineering tools.

中文翻译：

---

CRISPR：与进化生物学概念转变相关的基因组工程新原理

由于利用 Cas 蛋白的新一代基因组编辑工具取得了前所未有的成功，细菌和古菌适应性免疫的 CRISPR-Cas 系统已成为生物学家甚至公众家喻户晓的名字。然而，CRISPR-Cas 的基本生物学特征同样引起人们的兴趣，并且对我们理解抗病毒防御、宿主-寄生虫共同进化、自我与非自我歧视和适应机制的进化有重大影响。CRISPR-Cas 系统为拉马克进化提供了最著名的案例，即产生可遗传的、适应性的基因组变化以响应遇到外部因素，在这种情况下，外来核酸。CRISPR-Cas 系统采用多种机制来区分自我与非自我，但是，与一般免疫系统的情况一样，由于自身免疫无法完全消除，因此成本高昂。除了自身免疫之外，CRISPR-Cas 系统的适应性成本似乎取决于它们对水平基因转移的抑制作用，从而限制了进化创新。因此，CRISPR-Cas 基因座的动态进化经常被古细菌和细菌丢失和（重新）获得。CRISPR-Cas 的另一个基本生物学特征是它与微生物程序性细胞死亡和休眠诱导的密切联系。在这个免疫系统中，可能还有其他免疫系统，主动免疫反应似乎与不同形式的防御相结合，即细胞功能的“利他”关闭，从而保护邻近细胞。最后，对 Cas 蛋白进化联系的分析揭示了移动遗传元件 (MGE) 对 CRISPR-Cas 系统各种组件起源的多种贡献，此外，通过基因组操作发挥作用的不同生物系统似乎是从不相关的 MGE 趋同进化而来的。自适应防御系统和 MGE 的共同特征，即识别和切割基因组中独特位点的能力，使它们成为基因组编辑和工程工具的理想候选者。