
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.21.608784
preprint
1
Article
Exploring the diversity of anti-defense systems across prokaryotes, phages, and mobile genetic elements
Tesson Florian http://orcid.org/0000-0003-4038-1154

Huiting Erin http://orcid.org/0000-0002-5454-2679

Wei Linlin
Ren Jie
Johnson Matthew C. http://orcid.org/0000-0003-4534-5697

Planel Remi http://orcid.org/0000-0002-7826-3316

Cury Jean http://orcid.org/0000-0002-6462-8783

Feng Yue http://orcid.org/0000-0002-1576-1385

Bondy-Denomy Joseph http://orcid.org/0000-0002-4909-9481

Bernheim Aude http://orcid.org/0000-0003-0212-777X

21 8 2024
2024.08.21.608784https://creativecommons.org/licenses/by-nd/4.0/ This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use.
http://biorxiv.org/lookup/doi/10.1101/2024.08.21.608784
nihpp-2024.08.21.608784.pdf
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 E. coli 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.
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