Sarre, Luke A.Kim, Iana V.Ovchinnikov, VladimirOlivetta, MarineSuga, HiroshiDudin, OmayaSebé-Pedrós, ArnauMendoza, Alex de2024-09-202024-09-202024Sarre LA, Kim IV, Ovchinnikov V, Olivetta M, Suga H, Dudin O, et al. DNA methylation enables recurrent endogenization of giant viruses in an animal relative. Sci Adv. 2024 Jul 12;10(28):eado6406. DOI: 10.1126/sciadv.ado64062375-2548http://hdl.handle.net/10230/611875-Methylcytosine (5mC) is a widespread silencing mechanism that controls genomic parasites. In eukaryotes, 5mC has gained complex roles in gene regulation beyond parasite control, yet 5mC has also been lost in many lineages. The causes for 5mC retention and its genomic consequences are still poorly understood. Here, we show that the protist closely related to animals Amoebidium appalachense features both transposon and gene body methylation, a pattern reminiscent of invertebrates and plants. Unexpectedly, hypermethylated genomic regions in Amoebidium derive from viral insertions, including hundreds of endogenized giant viruses, contributing 14% of the proteome. Using a combination of inhibitors and genomic assays, we demonstrate that 5mC silences these giant virus insertions. Moreover, alternative Amoebidium isolates show polymorphic giant virus insertions, highlighting a dynamic process of infection, endogenization, and purging. Our results indicate that 5mC is critical for the controlled coexistence of newly acquired viral DNA into eukaryotic genomes, making Amoebidium a unique model to understand the hybrid origins of eukaryotic DNA.application/pdfengCopyright © 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). This is an open-access article distributed under the terms of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Regulació genèticainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1126/sciadv.ado6406info:eu-repo/semantics/openAccess