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Asgard archaea defense systems and their roles in the origin of immunity in eukaryotes

View ORCID ProfilePedro Leão, Mary E. Little, Kathryn E. Appler, Daphne Sahaya, Emily Aguilar-Pine, Kathryn Currie, View ORCID ProfileIlya J. Finkelstein, View ORCID ProfileValerie De Anda, View ORCID ProfileBrett J. Baker
doi: https://doi.org/10.1101/2023.09.13.557551
Pedro Leão
1Department of Integrative Biology, University of Texas at Austin, TX, USA
2Department of Marine Science, Marine Science Institute, University of Texas at Austin, Port Aransas, TX, USA
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  • ORCID record for Pedro Leão
  • For correspondence: pedro.leao.ru{at}gmail.com acidophile{at}gmail.com
Mary E. Little
3Department of Molecular Biosciences, University of Texas at Austin, TX, USA
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Kathryn E. Appler
1Department of Integrative Biology, University of Texas at Austin, TX, USA
2Department of Marine Science, Marine Science Institute, University of Texas at Austin, Port Aransas, TX, USA
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Daphne Sahaya
3Department of Molecular Biosciences, University of Texas at Austin, TX, USA
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Emily Aguilar-Pine
1Department of Integrative Biology, University of Texas at Austin, TX, USA
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Kathryn Currie
1Department of Integrative Biology, University of Texas at Austin, TX, USA
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Ilya J. Finkelstein
3Department of Molecular Biosciences, University of Texas at Austin, TX, USA
4Center for Systems and Synthetic Biology, University of Texas at Austin, TX, USA
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Valerie De Anda
1Department of Integrative Biology, University of Texas at Austin, TX, USA
2Department of Marine Science, Marine Science Institute, University of Texas at Austin, Port Aransas, TX, USA
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Brett J. Baker
1Department of Integrative Biology, University of Texas at Austin, TX, USA
2Department of Marine Science, Marine Science Institute, University of Texas at Austin, Port Aransas, TX, USA
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  • For correspondence: pedro.leao.ru{at}gmail.com acidophile{at}gmail.com
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Abstract

Immune systems are integral to survival against viral infection. Recently, dozens of new anti-viral systems have been characterized in bacteria1. Some of these systems are present in eukaryotes and appear to have originated in prokaryotes. However, little is known about these defense mechanisms in archaea. Here, we identified 2,610 complete defense systems in archaea related to eukaryotes, the Asgardarchaeota2. These comprise 89 unique systems, including argonaute, NLR, mokosh, viperin, lassamu, and CBASS. Asgard viperin (asVip) and argonaute (asAgo) proteins are present at high frequencies compared to bacteria and have structural homology to eukaryotes. Phylogenetic analyses revealed asVips are ancestral eukaryotic proteins. Heterologous expression of asVips in bacteria, including the lineage closest to eukaryotes, Hodarchaeales, showed robust anti-phage activity. Eukaryotic-and bacterial-argonaute proteins appear to have originated in the Asgardarchaeota, and have ancient structural characteristics. AsAgos appear to have argonaute-PIWI domains which are key components of the RNA interference (RNAi) in eukaryotes. Characterization of hundreds of new defense systems in the Asgardarchaeota revealed these archaea played important roles in the innovation of viral protection in eukaryotes. Given their relationship to eukaryotes, these defense systems may have applications in biomedicine and biotechnology.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted September 13, 2023.
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Asgard archaea defense systems and their roles in the origin of immunity in eukaryotes
Pedro Leão, Mary E. Little, Kathryn E. Appler, Daphne Sahaya, Emily Aguilar-Pine, Kathryn Currie, Ilya J. Finkelstein, Valerie De Anda, Brett J. Baker
bioRxiv 2023.09.13.557551; doi: https://doi.org/10.1101/2023.09.13.557551
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Asgard archaea defense systems and their roles in the origin of immunity in eukaryotes
Pedro Leão, Mary E. Little, Kathryn E. Appler, Daphne Sahaya, Emily Aguilar-Pine, Kathryn Currie, Ilya J. Finkelstein, Valerie De Anda, Brett J. Baker
bioRxiv 2023.09.13.557551; doi: https://doi.org/10.1101/2023.09.13.557551

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