Tesson Florian, Huiting Erin, Wei Linlin, Ren Jie, Johnson Matthew, Planel Rémi, Cury Jean, Feng Yue, Bondy-Denomy Joseph, Bernheim Aude
Institut Pasteur, CNRS UMR3525, Molecular Diversity of Microbes Lab, Paris, France.
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, 94158, USA.
bioRxiv. 2024 Aug 21:2024.08.21.608784. doi: 10.1101/2024.08.21.608784.
The co-evolution of prokaryotes, phages, and mobile genetic elements (MGEs) over the past billions of years has driven the emergence and diversification of defense and anti-defense systems alike. Anti-defense proteins have diverse functional domains, sequences, and are typically small, creating a challenge to detect anti-defense homologs across the prokaryotic genomes. To date, no tools comprehensively annotate anti-defense proteins within a desired genome or MGE. Here, we developed "AntiDefenseFinder" - a free open-source tool and web service that detects 156 anti-defense systems (of one or more proteins) in any genomic sequence. Using this dataset, we identified 47,981 anti-defense systems distributed across prokaryotes, phage, and MGEs. We found that some genes co-localize in "anti-defense islands", including T4 and Lambda phages, although many are standalone. Out of the 112 systems detected in bacteria, 100 systems localize only or preferentially in prophages, plasmids, phage satellites, integrons, and integrative and conjugative elements. However, over 80% of anti-Pycsar protein 1 (Apyc1) resides in non-mobile regions of bacteria. Evolutionary and functional analyses revealed that Apyc1 likely originated in bacteria to regulate cNMP signaling, but was co-opted multiple times by phages to overcome cNMP-utilizing defenses. With the AntiDefenseFinder tool, we hope to facilitate the identification of the full repertoire of anti-defense systems in MGEs, the discovery of new protein functions, and a deeper understanding of host-pathogen arms race.
在过去数十亿年里，原核生物、噬菌体和移动遗传元件（MGEs）的共同进化推动了防御和反防御系统的出现与多样化。反防御蛋白具有多样的功能结构域、序列，且通常较小，这给在原核生物基因组中检测反防御同源物带来了挑战。迄今为止，尚无工具能全面注释目标基因组或MGE中的反防御蛋白。在此，我们开发了“反防御蛋白查找器（AntiDefenseFinder）”——一种免费的开源工具和网络服务，可在任何基因组序列中检测156种反防御系统（由一种或多种蛋白质组成）。利用该数据集，我们在原核生物、噬菌体和MGEs中鉴定出47,981个反防御系统。我们发现，一些基因共定位于“反防御岛”，包括T4和λ噬菌体，尽管许多是独立存在的。在细菌中检测到的112个系统中，有100个系统仅或优先定位于前噬菌体、质粒、噬菌体卫星、整合子以及整合性接合元件中。然而，超过80%的抗Pycsar蛋白1（Apyc1）位于细菌的非移动区域。进化和功能分析表明，Apyc1可能起源于细菌以调节环核苷酸信号传导，但多次被噬菌体利用以克服利用环核苷酸的防御机制。借助反防御蛋白查找器工具，我们希望促进对MGEs中反防御系统全部组成的鉴定、新蛋白质功能的发现以及对宿主 - 病原体军备竞赛的更深入理解。
