Abstract
Evolutionary arms races between cells and viruses drive the rapid diversification of antiviral genes in diverse life forms. Recent discoveries have revealed the existence of immune genes that are shared between prokaryotes and eukaryotes and show molecular and mechanistic similarities in their response to viruses. However, the evolutionary dynamics underlying the conservation and adaptation of these antiviral genes remain mostly unexplored. Here, we show that viperins constitute a highly conserved family of immune genes across diverse prokaryotes and eukaryotes and identify mechanisms by which they diversified in eukaryotes. Our findings indicate that viperins are enriched in Asgard archaea and widely distributed in all major eukaryotic clades, suggesting their presence in the last eukaryotic common ancestor and their acquisition in eukaryotes from an archaeal lineage. We show that viperins maintain their immune function by producing antiviral nucleotide analogues and demonstrate that eukaryotic viperins diversified through serial innovations on the viperin gene, such as the emergence and selection of substrate specificity towards pyrimidine nucleotides, and through partnerships with genes maintained through genetic linkage, notably with nucleotide kinases. These findings unveil biochemical and genomic transitions underlying the adaptation of immune genes shared by prokaryotes and eukaryotes. Our study paves the way for further understanding of the conservation of immunity across domains of life.
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Data availability
Data used for this study are available here: https://github.com/mdmparis/viperins_evolution_2023 (ref. 68). Source data are provided with this paper.
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Acknowledgements
We thank members of the MDM laboratory, E. Rocha, T. Wein and B. Morehouse for useful comments on earlier versions of the manuscript. Several bioinformatic analyses were performed on the Core Cluster of the Institut Français de Bioinformatique (ANR-11-INBS-0013). To promote gender equality and inclusivity in research, we are convinced of the importance of acknowledging gender bias in research article citation. Using a custom script available at https://github.com/mdmparis/Estimating_gender_bias_in_references, we estimated that among the 67 references cited in the main text, approximately 24% (16) have a female first author and approximately 10% (seven) have a female last author. H.G., F.T., M.G., H.S. and A.B. are supported by the CRI Research Fellowship to A.B. from the Bettencourt Schueller Foundation, the ATIP-Avenir programme from INSERM (R21042KS/RSE22002KSA), the Emergence programme from the University of Paris-Cité (RSFVJ21IDXB6_DANA) and an ERC Starting Grant (no. PECAN 101040529). H.S. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no 945298-ParisRegionFP. Y.F. is supported by ZJU-HIC start-up grants. F.W. is supported by a National Science Foundation of China grant (no. 32370003).
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Y.F. and F.T. performed computational analyses for detection of antiphage defence systems in archaeal genomes. Y.F., J.C., F.T., H.S., H.G. and F.W. performed computational analyses related to viperin detection and phylogeny. F.W. provided AsgVip plasmids. H.S. and H.G. constructed strains and performed all experiments with assistance from B.O. and M.G. H.S. analysed mass spectrometry data, performed structural analyses and designed mutated viperins. H.S. and H.G. performed computational analyses of N-terminal tails, H.G. performed analyses of viperin-fused domains, and Y.F. and J.C. performed computational analyses of viperin-associated nucleotide kinases. F.W. and A.B. supervised the project. H.S., H.G., F.W. and A.B. wrote the manuscript. All authors contributed to the review of the manuscript and provided final approval of the work.
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H.G. is employed by Generare Bioscience. The other authors declare no competing interests.
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Shomar, H., Georjon, H., Feng, Y. et al. Viperin immunity evolved across the tree of life through serial innovations on a conserved scaffold. Nat Ecol Evol 8, 1667–1679 (2024). https://doi.org/10.1038/s41559-024-02463-z
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DOI: https://doi.org/10.1038/s41559-024-02463-z
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