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            <title xml:lang="en">Conservation of antiviral systems across domains of life reveals immune genes in humans</title>
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                <forename type="first">Jean</forename>
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                <forename type="first">Matthieu</forename>
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                <forename type="first">Enzo</forename>
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                <forename type="first">Aude</forename>
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                <forename>Matthieu</forename>
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            <funder>The bioinformatic analysis were performed on the Core Cluster of the Institut Français de Bioinformatique (IFB) (ANR-11-INBS-0013). .C., E.M., F.T., M.H. and A.B are supported by the CRI Research Fellowship to Aude Bernheim from the Bettencourt Schueller Foundation, the ATIP-Avenir program from INSERM (R21042KS/RSE22002KSA), the Emergence program from the University of Paris-Cité (RSFVJ21IDXB6_DANA) and ERC Starting Grant (PECAN 101040529). E.Z.P, V.H.T, D.B. and M.H. are supported by an ERC Starting Grant (STEMGUARD 101075865), a grant from Paris Sciences et Lettres University (Amorçage Jeunes Équipes), and funding from Institut Curie. This work has received support under the program France 2030 launched by the French Government (ANR-10-IDEX-0001-02 PSL). A. H. is supported by a fellowship from FRM. G.O. is supported by an EMBO Long-Term Fellowship (ALTF 851-2021). P.B. is supported by grants from Agence Nationale de Recherche contre le SIDA et les hépatites virales (ANRS), from Ensemble contre le SIDA (Sidaction) and from Laboratoire d’Excellence (Labex) DCBIOL (ANR-10-IDEX-0001-02 PSL and ANR- 11-LABX-0043). M.R. and L.Q.M. are supported by the Institut Pasteur, the Collège de France, the Centre Nationale de la Recherche Scientifique (CNRS), the Agence Nationale de la Recherche (ANR) grants POPCELL-REG (ANR-22-CE12-0030-01), COVIFERON (ANR-21-RHUS-08), and France 2030-EPIGEMI (ANR-23-CHBS-0007), and the French Government’s Investissement d’Avenir program, Laboratoires d’Excellence “Milieu Intérieur” (ANR-10-LABX-69-01).</funder>
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                <title xml:lang="en">Conservation of antiviral systems across domains of life reveals immune genes in humans</title>
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                    <forename type="first">Enzo</forename>
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                    <forename type="first">Aude</forename>
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                  <date type="datePub">2024-09-11</date>
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                <term xml:lang="en">GIMAPs</term>
                <term xml:lang="en">Lamassu</term>
                <term xml:lang="en">Eleos</term>
                <term xml:lang="en">piRNA pathway</term>
                <term xml:lang="en">Mokosh</term>
                <term xml:lang="en">human antiviral proteins</term>
                <term xml:lang="en">antiphage systems</term>
                <term xml:lang="en">ancestral immunity</term>
                <term xml:lang="en">evolution</term>
                <term xml:lang="en">immunology</term>
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              <p>Deciphering the immune organization of eukaryotes is of importance for human health and for the understanding of ecosystems. The recent discovery of dozens novel antiphage systems revealed that various eukaryotic immune proteins originate from prokaryotic antiphage systems. Whether antiphage proteins of bacteria can be utilized to discover immune proteins in eukaryotes remains unexplored. Here, we use a phylogenydriven approach to uncover novel eukaryotic immune proteins by searching for homologs of bacterial antiphage systems. We demonstrate that proteins displaying sequence similarity with recently discovered antiphage systems are widespread in eukaryotes, and maintain a role in immunity in humans. Two eukaryotic proteins of the anti-transposon piRNA pathway are evolutionary linked to the antiphage system Mokosh. We uncover and experimentally validate human antiviral genes which are related to the Eleos and Lamassu prokaryotic systems. Our work illustrates how comparative genomics of immune mechanisms can be employed to uncover defence genes in eukaryotes.</p>
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