Abstract
Cold seeps host diverse microbes and viruses with numerous unexplored defense and anti-defense systems. Analysis of 3813 microbial and 13,336 viral genomes from 191 metagenomes across 17 cold seep sites reveals extensive microbial defense repertoires, with over 60% representing candidate systems. Experimental validation confirms that several candidates protect against viral infection. These defense systems frequently co-occur, suggesting potential synergistic interactions, and are broadly distributed across sediments. In response, viruses have evolved diverse anti-defense genes, and the concurrent presence of multiple viral and microbial systems highlights intricate coevolution. Functionally critical lineages, such as anaerobic methanotrophic archaea, sulfate-reducing bacteria, and diazotrophs, appear to modify their defensive strategies under ecological and environmental pressures; for example, sulfate-reducing bacteria harbor multiple Gabija systems while corresponding viruses carry anti-Gabija genes, illustrating specific coevolutionary adaptations. Overall, these findings underscore the critical role of virus-microbe interactions in shaping microbial metabolic functions and environmental adaptation in deep-sea ecosystems.
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Data availability
The metagenomic data analyzed in this study are available from our previous publication65 and the NCBI BioProject ID PRJNA1169195 (Supplementary Data 17). The metatranscriptomic raw reads are available under NCBI BioProject IDs PRJNA738468, PRJNA739005, and PRJNA831433 (Supplementary Data 18). The non-redundant MAG catalogue and viral genomes are available under NCBI BioProject PRJNA950938. Accession numbers of the protein sequences used to construct the custom database for identifying anti-defence genes are provided in Supplementary Data 19. Protein sequences corresponding to defence systems, candidate defence systems, and anti-defence systems have been deposited in the GSA database under BioProject PRJCA052411105,106. Phylogenetic trees of GajAB based on amino acid sequences and protein structural analyses generated in this study are available on Figshare at (https://doi.org/10.6084/m9.figshare.27004438). All additional data supporting the findings of this study are provided within the article and its Supplementary Information files. Source data are provided with this paper.
Code availability
The present study did not generate codes, and mentioned tools used for the data analysis were applied with default parameters unless specified otherwise.
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Acknowledgements
The work was supported by National Key R&D Program of China (No. 2024YFC2816200 to X.D.), National Science Foundation of China (No. 42376115 to X.D., No. 42406109 to Y.H., No. 32470036 to R.C. and No. 32100025 to R.C.), Natural Science Foundation Project of Xiamen City (No. 3502Z202373076 to X.D.), Natural Science Foundation of Fujian Province (No. 2023J06042 to X.D.), Scientific Research Foundation of Third Institute of Oceanography, MNR (No. 2022025 to X.D., No. 2023022 to X.D. and No. 2025013 to Y.H.), Open Funding Project of State Key Laboratory of Microbial Metabolism (No. MMLKF23-05 to X.D.) and Fundamental Research Funds for the Central Universities (No. 2662025SYPY003 to R.C.).
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X.D. conceived and designed the study. Y.H. and J.L. performed the omics analyses. C.L. contributed to viral identification and classification. R.C. designed and conducted the experimental implementations. X.L. participated in the analysis of some metagenomic data. C.L., F.X., J.P. and W.X. actively participated in discussions and data interpretation. F.W. and H.J. provided valuable suggestions for manuscript revision. Y.H., J.L. and X.D. wrote the manuscript with input from all authors.
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Han, Y., Liao, J., Li, C. et al. Co-occurrence of diverse defense systems shapes complex microbe-virus relationships in deep-sea cold seeps. Nat Commun (2026). https://doi.org/10.1038/s41467-025-68174-6
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DOI: https://doi.org/10.1038/s41467-025-68174-6
