研究小组在细菌中发现了编码一种预测的核酸酶的基因，这种核酸酶与一种胰蛋白酶样蛋白酶配对，这种酶被多个不相关的抗病毒免疫系统反复获得。细胞基础和生化分析表明，核酸酶是一种前酶，只有在其伴侣蛋白酶激活后才能切割DNA。两种不同的免疫系统，Hachiman和AVAST（抗病毒腺苷三磷酸酶/核苷三磷酸酶的STAND超家族，Avs），尽管它们独立的进化起源，但具有相同的蛋白水解激活机制。核酸酶-蛋白酶遗传模式的检查鉴定了caspase-核酸酶（canu）基因组位点，这些位点在一种让人想起真核caspase激活的途径中赋予抗病毒防御。这些结果揭示了前核酸酶及其激活蛋白酶在不同免疫系统中的协调活动，并显示了共同进化如何使防御系统创新。
据了解，抗病毒免疫系统通过将新基因整合到现有途径中，创造新的病毒抗性机制来实现多样化。
附：英文原文
Title: Recurrent acquisition of nuclease-protease pairs in antiviral immunity
Author: Owen T. Tuck, Jason J. Hu, Santiago C. Lopez, Benjamin A. Adler, Claire E. O’Brien, Kendall Hsieh, Charlotte Meredith, Kenneth J. Loi, Peter H. Yoon, Erin E. Doherty, Arushi Lahiri, Jennifer A. Doudna
Issue&Volume: 2025-11-13
Abstract: Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin-like protease repeatedly acquired by multiple, otherwise unrelated antiviral immune systems in bacteria. Cell-based and biochemical assays revealed the nuclease is a proenzyme that cleaves DNA only after activation by its partner protease. Two distinct immune systems, Hachiman and AVAST (antiviral adenosine triphosphatase/nucleoside triphosphatase of the STAND superfamily, Avs), use the same mechanism of proteolytic activation despite their independent evolutionary origins. Examination of nuclease-protease inheritance patterns identified caspase-nuclease (canu) genomic loci that confer antiviral defense in a pathway reminiscent of eukaryotic caspase activation. These results uncover the coordinated activities of pro-nucleases and their activating proteases within different immune systems and show how coevolution enables defense system innovation.
DOI: aea8769
Source: https://www.science.org/doi/10.1126/science.aea8769