{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T03:38:12Z","timestamp":1793936292575,"version":"4.8.0"},"reference-count":95,"publisher":"Springer Science and Business Media LLC","issue":"8127","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2026,8,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The origin of eukaryotes remains a central enigma in biology\n                    <jats:sup>1<\/jats:sup>\n                    . Continuing debates agree on the pivotal role of a symbiosis between an alphaproteobacterium and an Asgard archaeon\n                    <jats:sup>2,3<\/jats:sup>\n                    . However, the nature, timing and contributions of other potential bacterial partners\n                    <jats:sup>4\u20136<\/jats:sup>\n                    and the role of interactions with viruses\n                    <jats:sup>7\u20139<\/jats:sup>\n                    remain contentious. To address these questions, we used advanced phylogenomic approaches and comprehensive datasets spanning the known diversity of cellular life and viruses. Our analysis provided a revised reconstruction of the last eukaryotic common ancestor (LECA) proteome, in which we traced the phylogenetic origin of each protein family. We found compelling evidence for multiple waves of horizontal gene transfer from diverse bacterial donors, with some likely to have preceded mitochondrial endosymbiosis. We inferred plausible traits of the major donors and their functional contributions to the LECA. Our findings support a contribution of horizontal gene transfers to shaping the proteomes of pre-LECA ancestors and suggest a facilitating role of\n                    <jats:italic>Nucleocytoviricota<\/jats:italic>\n                    viruses. Taken together, our results suggest that ancient eukaryotes may have originated within complex microbial ecosystems through a succession of diverse associations that left a footprint of horizontally transferred genes.\n                  <\/jats:p>","DOI":"10.1038\/s41586-026-10639-9","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:03:08Z","timestamp":1781103788000},"page":"399-405","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Gene ancestries reveal diverse microbial associations during eukaryogenesis"],"prefix":"10.1038","volume":"656","author":[{"given":"Mois\u00e8s","family":"Bernabeu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saioa","family":"Manzano-Morales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Marcet-Houben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0019-1735","authenticated-orcid":false,"given":"Toni","family":"Gabald\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"10639_CR1","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.tree.2015.09.005","volume":"30","author":"P L\u00f3pez-Garc\u00eda","year":"2015","unstructured":"L\u00f3pez-Garc\u00eda, P. & Moreira, D. Open questions on the origin of eukaryotes. Trends Ecol. Evol. 30, 697\u2013708 (2015).","journal-title":"Trends Ecol. Evol."},{"key":"10639_CR2","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1146\/annurev-micro-090817-062213","volume":"75","author":"T Gabald\u00f3n","year":"2021","unstructured":"Gabald\u00f3n, T. Origin and early evolution of the eukaryotic cell. Annu. Rev. Microbiol. 75, 631\u2013647 (2021).","journal-title":"Annu. Rev. Microbiol."},{"key":"10639_CR3","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/s41586-024-07677-6","volume":"633","author":"J Vosseberg","year":"2024","unstructured":"Vosseberg, J. et al. The emerging view on the origin and early evolution of eukaryotic cells. Nature 633, 295\u2013305 (2024).","journal-title":"Nature"},{"key":"10639_CR4","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nature16941","volume":"531","author":"AA Pittis","year":"2016","unstructured":"Pittis, A. A. & Gabald\u00f3n, T. Late acquisition of mitochondria by a host with chimaeric prokaryotic ancestry. Nature 531, 101\u2013104 (2016).","journal-title":"Nature"},{"key":"10639_CR5","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1038\/s41564-020-0710-4","volume":"5","author":"P L\u00f3pez-Garc\u00eda","year":"2020","unstructured":"L\u00f3pez-Garc\u00eda, P. & Moreira, D. The syntrophy hypothesis for the origin of eukaryotes revisited. Nat. Microbiol. 5, 655\u2013667 (2020).","journal-title":"Nat. Microbiol."},{"key":"10639_CR6","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1002\/iub.1950","volume":"70","author":"T Gabald\u00f3n","year":"2018","unstructured":"Gabald\u00f3n, T. Relative timing of mitochondrial endosymbiosis and the \u2018pre-mitochondrial symbioses\u2019 hypothesis. IUBMB Life 70, 1188\u20131196 (2018).","journal-title":"IUBMB Life"},{"key":"10639_CR7","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.coviro.2013.06.013","volume":"3","author":"P Forterre","year":"2013","unstructured":"Forterre, P. & Prangishvili, D. The major role of viruses in cellular evolution: facts and hypotheses. Curr. Opin. Virol. 3, 558\u2013565 (2013).","journal-title":"Curr. Opin. Virol."},{"key":"10639_CR8","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/s41564-021-01026-3","volume":"7","author":"NAT Irwin","year":"2022","unstructured":"Irwin, N. A. T., Pittis, A. A., Richards, T. A. & Keeling, P. J. Systematic evaluation of horizontal gene transfer between eukaryotes and viruses. Nat. Microbiol. 7, 327\u2013336 (2022).","journal-title":"Nat. Microbiol."},{"key":"10639_CR9","doi-asserted-by":"publisher","first-page":"19585","DOI":"10.1073\/pnas.1912006116","volume":"116","author":"J Guglielmini","year":"2019","unstructured":"Guglielmini, J., Woo, A. C., Krupovic, M., Forterre, P. & Gaia, M. Diversification of giant and large eukaryotic dsDNA viruses predated the origin of modern eukaryotes. Proc. Natl Acad. Sci. USA 116, 19585\u201319592 (2019).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10639_CR10","unstructured":"Stanier, R. Y., Doudoroff, M. & Adelberg, E. A. The Microbial World 2nd edn (Prentice Hall, 1965)."},{"key":"10639_CR11","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1091\/mbc.e16-07-0509","volume":"28","author":"MW Gray","year":"2017","unstructured":"Gray, M. W. Lynn Margulis and the endosymbiont hypothesis: 50 years later. Mol. Biol. Cell 28, 1285\u20131287 (2017).","journal-title":"Mol. Biol. Cell"},{"key":"10639_CR12","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1038\/s41586-023-06186-2","volume":"618","author":"L Eme","year":"2023","unstructured":"Eme, L. et al. Inference and reconstruction of the heimdallarchaeial ancestry of eukaryotes. Nature 618, 992\u2013999 (2023).","journal-title":"Nature"},{"key":"10639_CR13","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/nature21031","volume":"541","author":"K Zaremba-Niedzwiedzka","year":"2017","unstructured":"Zaremba-Niedzwiedzka, K. et al. Asgard archaea illuminate the origin of eukaryotic cellular complexity. Nature 541, 353\u2013358 (2017).","journal-title":"Nature"},{"key":"10639_CR14","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1126\/science.1085463","volume":"301","author":"T Gabald\u00f3n","year":"2003","unstructured":"Gabald\u00f3n, T. & Huynen, M. A. Reconstruction of the proto-mitochondrial metabolism. Science 301, 609 (2003).","journal-title":"Science"},{"key":"10639_CR15","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/s41586-018-0059-5","volume":"557","author":"J Martijn","year":"2018","unstructured":"Martijn, J., Vosseberg, J., Guy, L., Offre, P. & Ettema, T. J. G. Deep mitochondrial origin outside the sampled alphaproteobacteria. Nature 557, 101\u2013105 (2018).","journal-title":"Nature"},{"key":"10639_CR16","doi-asserted-by":"publisher","first-page":"e219","DOI":"10.1371\/journal.pcbi.0030219","volume":"3","author":"T Gabald\u00f3n","year":"2007","unstructured":"Gabald\u00f3n, T. & Huynen, M. A. From endosymbiont to host-controlled organelle: the hijacking of mitochondrial protein synthesis and metabolism. PLoS Comput. Biol. 3, e219 (2007).","journal-title":"PLoS Comput. Biol."},{"key":"10639_CR17","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1093\/molbev\/msm095","volume":"24","author":"D Pisani","year":"2007","unstructured":"Pisani, D., Cotton, J. A. & McInerney, J. O. Supertrees disentangle the chimerical origin of eukaryotic genomes. Mol. Biol. Evol. 24, 1752\u20131760 (2007).","journal-title":"Mol. Biol. Evol."},{"key":"10639_CR18","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1093\/molbev\/mst272","volume":"31","author":"NC Rochette","year":"2014","unstructured":"Rochette, N. C., Brochier-Armanet, C. & Gouy, M. Phylogenomic test of the hypotheses for the evolutionary origin of eukaryotes. Mol. Biol. Evol. 31, 832\u2013845 (2014).","journal-title":"Mol. Biol. Evol."},{"key":"10639_CR19","doi-asserted-by":"publisher","unstructured":"Cox, R. M. et al. Ancient eukaryotic protein interactions illuminate modern genetic traits and disorders. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2024.05.26.595818 (2024).","DOI":"10.1101\/2024.05.26.595818"},{"key":"10639_CR20","doi-asserted-by":"publisher","first-page":"e1007301","DOI":"10.1371\/journal.pcbi.1007301","volume":"15","author":"ES Deutekom","year":"2019","unstructured":"Deutekom, E. S., Vosseberg, J., van Dam, T. J. P. & Snel, B. Measuring the impact of gene prediction on gene loss estimates in Eukaryotes by quantifying falsely inferred absences. PLoS Comput. Biol. 15, e1007301 (2019).","journal-title":"PLoS Comput. Biol."},{"key":"10639_CR21","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/s41559-020-01320-z","volume":"5","author":"J Vosseberg","year":"2021","unstructured":"Vosseberg, J. et al. Timing the origin of eukaryotic cellular complexity with ancient duplications. Nat. Ecol. Evol. 5, 92\u2013100 (2021).","journal-title":"Nat. Ecol. Evol."},{"key":"10639_CR22","doi-asserted-by":"publisher","first-page":"D785","DOI":"10.1093\/nar\/gkab776","volume":"50","author":"DH Parks","year":"2022","unstructured":"Parks, D. H. et al. GTDB: an ongoing census of bacterial and archaeal diversity through a phylogenetically consistent, rank normalized and complete genome-based taxonomy. Nucleic Acids Res. 50, D785\u2013D794 (2022).","journal-title":"Nucleic Acids Res."},{"key":"10639_CR23","doi-asserted-by":"crossref","unstructured":"Goodacre, N., Aljanahi, A., Nandakumar, S., Mikailov, M. & Khan, A. S. A reference viral database (RVDB) to enhance bioinformatics analysis of high-throughput sequencing for novel virus detection. mSphere 3, e00069-18 (2018).","DOI":"10.1128\/mSphereDirect.00069-18"},{"key":"10639_CR24","doi-asserted-by":"publisher","unstructured":"Bernabeu, M., Manzano-Morales, S., Marcet-Houben, M. & Gabald\u00f3n, T. Data for: Gene ancestries reveal diverse microbial associations during eukaryogenesis. Zenodo https:\/\/doi.org\/10.5281\/zenodo.13897945 (2024).","DOI":"10.5281\/zenodo.13897945"},{"key":"10639_CR25","doi-asserted-by":"publisher","first-page":"e3002917","DOI":"10.1371\/journal.pbio.3002917","volume":"22","author":"TA Richards","year":"2024","unstructured":"Richards, T. A. et al. Reconstructing the last common ancestor of all eukaryotes. PLoS Biol. 22, e3002917 (2024).","journal-title":"PLoS Biol."},{"key":"10639_CR26","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1073\/pnas.032658599","volume":"99","author":"H Hartman","year":"2002","unstructured":"Hartman, H. & Fedorov, A. The origin of the eukaryotic cell: a genomic investigation. Proc. Natl Acad. Sci. USA 99, 1420\u20131425 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10639_CR27","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-5-209","volume":"11","author":"EV Koonin","year":"2010","unstructured":"Koonin, E. V. The origin and early evolution of eukaryotes in the light of phylogenomics. Genome Biol. 11, 209 (2010).","journal-title":"Genome Biol."},{"key":"10639_CR28","doi-asserted-by":"crossref","unstructured":"Bernabeu, M., Armero, C. & Gabald\u00f3n, T. Probabilistic modelling improves relative dating from gene phylogenies. Methods Ecol. Evol. 16, 2461\u20132471 (2025).","DOI":"10.1111\/2041-210X.70127"},{"key":"10639_CR29","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1038\/s41559-018-0683-3","volume":"2","author":"A Guti\u00e9rrez-Preciado","year":"2018","unstructured":"Guti\u00e9rrez-Preciado, A. et al. Functional shifts in microbial mats recapitulate early Earth metabolic transitions. Nat. Ecol. Evol. 2, 1700\u20131708 (2018).","journal-title":"Nat. Ecol. Evol."},{"key":"10639_CR30","doi-asserted-by":"crossref","unstructured":"Zhang, J. et al. Deep origin of eukaryotes outside Heimdallarchaeia within Asgardarchaeota. Nature 642, 990\u2013998 (2025).","DOI":"10.1038\/s41586-025-08955-7"},{"key":"10639_CR31","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/32096","volume":"392","author":"W Martin","year":"1998","unstructured":"Martin, W. & M\u00fcller, M. The hydrogen hypothesis for the first eukaryote. Nature 392, 37\u201341 (1998).","journal-title":"Nature"},{"key":"10639_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14853","volume":"8","author":"C Boedeker","year":"2017","unstructured":"Boedeker, C. et al. Determining the bacterial cell biology of Planctomycetes. Nat. Commun. 8, 14853 (2017).","journal-title":"Nat. Commun."},{"key":"10639_CR33","doi-asserted-by":"crossref","unstructured":"Wurzbacher, C. E. et al. \u201cCandidatus Uabimicrobium helgolandensis\u201d\u2014a planctomycetal bacterium with phagocytosis-like prey cell engulfment, surface-dependent motility, and cell division. MBio 15, e0204424 (2024).","DOI":"10.1128\/mbio.02044-24"},{"key":"10639_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13499-2","volume":"10","author":"T Shiratori","year":"2019","unstructured":"Shiratori, T., Suzuki, S., Kakizawa, Y. & Ishida, K.-I. Phagocytosis-like cell engulfment by a planctomycete bacterium. Nat. Commun. 10, 5529 (2019).","journal-title":"Nat. Commun."},{"key":"10639_CR35","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1126\/science.1196720","volume":"330","author":"DP Devos","year":"2010","unstructured":"Devos, D. P. & Reynaud, E. G. Evolution. Intermediate steps. Science 330, 1187\u20131188 (2010).","journal-title":"Science"},{"key":"10639_CR36","doi-asserted-by":"publisher","first-page":"3531","DOI":"10.1093\/molbev\/msab186","volume":"38","author":"DP Devos","year":"2021","unstructured":"Devos, D. P. Reconciling Asgardarchaeota phylogenetic proximity to eukaryotes and Planctomycetes cellular features in the evolution of life. Mol. Biol. Evol. 38, 3531\u20133542 (2021).","journal-title":"Mol. Biol. Evol."},{"key":"10639_CR37","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1002\/bies.201100045","volume":"33","author":"JO McInerney","year":"2011","unstructured":"McInerney, J. O. et al. Planctomycetes and eukaryotes: a case of analogy not homology. Bioessays 33, 810\u2013817 (2011).","journal-title":"Bioessays"},{"key":"10639_CR38","doi-asserted-by":"publisher","first-page":"16034","DOI":"10.1038\/nmicrobiol.2016.34","volume":"1","author":"FL Sousa","year":"2016","unstructured":"Sousa, F. L., Neukirchen, S., Allen, J. F., Lane, N. & Martin, W. F. Lokiarchaeon is hydrogen dependent. Nat. Microbiol. 1, 16034 (2016).","journal-title":"Nat. Microbiol."},{"key":"10639_CR39","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1038\/s41564-019-0406-9","volume":"4","author":"A Spang","year":"2019","unstructured":"Spang, A. et al. Proposal of the reverse flow model for the origin of the eukaryotic cell based on comparative analyses of Asgard archaeal metabolism. Nat. Microbiol. 4, 1138\u20131148 (2019).","journal-title":"Nat. Microbiol."},{"key":"10639_CR40","first-page":"943","volume":"34","author":"SA Mu\u00f1oz-G\u00f3mez","year":"2017","unstructured":"Mu\u00f1oz-G\u00f3mez, S. A., Wideman, J. G., Roger, A. J. & Slamovits, C. H. The origin of mitochondrial cristae from Alphaproteobacteria. Mol. Biol. Evol. 34, 943\u2013956 (2017).","journal-title":"Mol. Biol. Evol."},{"key":"10639_CR41","first-page":"1943","volume":"273","author":"T Cavalier-Smith","year":"2006","unstructured":"Cavalier-Smith, T. Origin of mitochondria by intracellular enslavement of a photosynthetic purple bacterium. Proc. Biol. Sci. 273, 1943\u20131952 (2006).","journal-title":"Proc. Biol. Sci."},{"key":"10639_CR42","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/s41586-019-1916-6","volume":"577","author":"H Imachi","year":"2020","unstructured":"Imachi, H. et al. Isolation of an archaeon at the prokaryote\u2013eukaryote interface. Nature 577, 519\u2013525 (2020).","journal-title":"Nature"},{"key":"10639_CR43","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/s41586-022-05550-y","volume":"613","author":"T Rodrigues-Oliveira","year":"2023","unstructured":"Rodrigues-Oliveira, T. et al. Actin cytoskeleton and complex cell architecture in an Asgard archaeon. Nature 613, 332\u2013339 (2023).","journal-title":"Nature"},{"key":"10639_CR44","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-022-01421-w","volume":"10","author":"H Du","year":"2022","unstructured":"Du, H. et al. Microbial active functional modules derived from network analysis and metabolic interactions decipher the complex microbiome assembly in mangrove sediments. Microbiome 10, 224 (2022).","journal-title":"Microbiome"},{"key":"10639_CR45","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1038\/s41564-023-01378-y","volume":"8","author":"M Krupovic","year":"2023","unstructured":"Krupovic, M., Dolja, V. V. & Koonin, E. V. The virome of the last eukaryotic common ancestor and eukaryogenesis. Nat. Microbiol. 8, 1008\u20131017 (2023).","journal-title":"Nat. Microbiol."},{"key":"10639_CR46","doi-asserted-by":"publisher","first-page":"198168","DOI":"10.1016\/j.virusres.2020.198168","volume":"289","author":"PJL Bell","year":"2020","unstructured":"Bell, P. J. L. Evidence supporting a viral origin of the eukaryotic nucleus. Virus Res. 289, 198168 (2020).","journal-title":"Virus Res."},{"key":"10639_CR47","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.mib.2016.02.001","volume":"31","author":"P Forterre","year":"2016","unstructured":"Forterre, P. & Ga\u00efa, M. Giant viruses and the origin of modern eukaryotes. Curr. Opin. Microbiol. 31, 44\u201349 (2016).","journal-title":"Curr. Opin. Microbiol."},{"key":"10639_CR48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001430","volume":"19","author":"FO Aylward","year":"2021","unstructured":"Aylward, F. O., Moniruzzaman, M., Ha, A. D. & Koonin, E. V. A phylogenomic framework for charting the diversity and evolution of giant viruses. PLoS Biol. 19, e3001430 (2021).","journal-title":"PLoS Biol."},{"key":"10639_CR49","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s00239-025-10246-8","volume":"93","author":"S Karki","year":"2025","unstructured":"Karki, S., Barth, Z. K. & Aylward, F. O. Ancient host-virus gene transfer hints at a diverse pre-LECA virosphere. J. Mol. Evol. 93, 295\u2013305 (2025).","journal-title":"J. Mol. Evol."},{"key":"10639_CR50","doi-asserted-by":"publisher","first-page":"e3002460","DOI":"10.1371\/journal.pbio.3002460","volume":"22","author":"M Bernabeu","year":"2024","unstructured":"Bernabeu, M., Manzano-Morales, S. & Gabald\u00f3n, T. On the impact of incomplete taxon sampling on the relative timing of gene transfer events. PLoS Biol. 22, e3002460 (2024).","journal-title":"PLoS Biol."},{"key":"10639_CR51","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1093\/molbev\/msaa054","volume":"37","author":"C Santana-Molina","year":"2020","unstructured":"Santana-Molina, C., Rivas-Marin, E., Rojas, A. M. & Devos, D. P. Origin and evolution of polycyclic triterpene synthesis. Mol. Biol. Evol. 37, 1925\u20131941 (2020).","journal-title":"Mol. Biol. Evol."},{"key":"10639_CR52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2101276118","volume":"118","author":"Y Hoshino","year":"2021","unstructured":"Hoshino, Y. & Gaucher, E. A. Evolution of bacterial steroid biosynthesis and its impact on eukaryogenesis. Proc. Natl Acad. Sci. USA 118, e2101276118 (2021).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10639_CR53","first-page":"335","volume":"90","author":"H Bolhuis","year":"2014","unstructured":"Bolhuis, H., Cretoiu, M. S. & Stal, L. J. Molecular ecology of microbial mats. FEMS Microbiol. Ecol. 90, 335\u2013350 (2014).","journal-title":"FEMS Microbiol. Ecol."},{"key":"10639_CR54","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1093\/gbe\/evy014","volume":"10","author":"MW Brown","year":"2018","unstructured":"Brown, M. W. et al. Phylogenomics places orphan protistan lineages in a novel eukaryotic super-group. Genome Biol. Evol. 10, 427\u2013433 (2018).","journal-title":"Genome Biol. Evol."},{"key":"10639_CR55","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/s41586-018-0708-8","volume":"564","author":"G Lax","year":"2018","unstructured":"Lax, G. et al. Hemimastigophora is a novel supra-kingdom-level lineage of eukaryotes. Nature 564, 410\u2013414 (2018).","journal-title":"Nature"},{"key":"10639_CR56","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1038\/s41586-022-05511-5","volume":"612","author":"DV Tikhonenkov","year":"2022","unstructured":"Tikhonenkov, D. V. et al. Microbial predators form a new supergroup of eukaryotes. Nature 612, 714\u2013719 (2022).","journal-title":"Nature"},{"key":"10639_CR57","doi-asserted-by":"crossref","unstructured":"Torruella, G., Galindo, L. J., Moreira, D. & L\u00f3pez-Garc\u00eda, P. Phylogenomics of neglected flagellated protists supports a revised eukaryotic tree of life. Curr. Biol. 35, 198\u2013207.e4 (2025)","DOI":"10.1016\/j.cub.2024.10.075"},{"key":"10639_CR58","doi-asserted-by":"crossref","unstructured":"Williamson, K. et al. A robustly rooted tree of eukaryotes reveals their excavate ancestry. Nature 640, 974\u2013981 (2025).","DOI":"10.1038\/s41586-025-08709-5"},{"key":"10639_CR59","doi-asserted-by":"crossref","unstructured":"Burki, F., Roger, A. J., Brown, M. W. & Simpson, A. G. B. The new tree of eukaryotes. Trends Ecol. Evol. 35, 43\u201355 (2020).","DOI":"10.1016\/j.tree.2019.08.008"},{"key":"10639_CR60","doi-asserted-by":"publisher","first-page":"D73","DOI":"10.1093\/nar\/gkv1226","volume":"44","author":"PA Kitts","year":"2016","unstructured":"Kitts, P. A. et al. Assembly: a resource for assembled genomes at NCBI. Nucleic Acids Res. 44, D73\u201380 (2016).","journal-title":"Nucleic Acids Res."},{"key":"10639_CR61","doi-asserted-by":"crossref","unstructured":"Richter, D. J. et al. EukProt: a database of genome-scale predicted proteins across the diversity of eukaryotes. Peer Community J. 2, e56 (2022).","DOI":"10.24072\/pcjournal.173"},{"key":"10639_CR62","doi-asserted-by":"publisher","first-page":"D747","DOI":"10.1093\/nar\/gkad992","volume":"52","author":"X Gao","year":"2024","unstructured":"Gao, X. et al. The P10K database: a data portal for the protist 10 000 genomes project. Nucleic Acids Res. 52, D747\u2013D755 (2024).","journal-title":"Nucleic Acids Res."},{"key":"10639_CR63","doi-asserted-by":"publisher","first-page":"D523","DOI":"10.1093\/nar\/gkac1052","volume":"51","author":"UniProt Consortium","year":"2023","unstructured":"UniProt Consortium UniProt: the Universal Protein Knowledgebase in 2023. Nucleic Acids Res. 51, D523\u2013D531 (2023).","journal-title":"Nucleic Acids Res."},{"key":"10639_CR64","doi-asserted-by":"publisher","first-page":"D891","DOI":"10.1093\/nar\/gkad1049","volume":"52","author":"PW Harrison","year":"2024","unstructured":"Harrison, P. W. et al. Ensembl 2024. Nucleic Acids Res. 52, D891\u2013D899 (2024).","journal-title":"Nucleic Acids Res."},{"key":"10639_CR65","doi-asserted-by":"crossref","unstructured":"Wong, E. D. et al. Saccharomyces genome database update: server architecture, pan-genome nomenclature, and external resources. Genetics 224, iyac191 (2023).","DOI":"10.1093\/genetics\/iyac191"},{"key":"10639_CR66","doi-asserted-by":"publisher","first-page":"3210","DOI":"10.1093\/bioinformatics\/btv351","volume":"31","author":"FA Sim\u00e3o","year":"2015","unstructured":"Sim\u00e3o, F. A., Waterhouse, R. M., Ioannidis, P., Kriventseva, E. V. & Zdobnov, E. M. BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs. Bioinformatics 31, 3210\u20133212 (2015).","journal-title":"Bioinformatics"},{"key":"10639_CR67","doi-asserted-by":"publisher","first-page":"e191","DOI":"10.1002\/imt2.191","volume":"3","author":"W Shen","year":"2024","unstructured":"Shen, W., Sipos, B. & Zhao, L. SeqKit2: a Swiss army knife for sequence and alignment processing. Imeta 3, e191 (2024).","journal-title":"Imeta"},{"key":"10639_CR68","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/0097-8485(93)85006-X","volume":"17","author":"JC Wootton","year":"1993","unstructured":"Wootton, J. C. & Federhen, S. Statistics of local complexity in amino acid sequences and sequence databases. Comput. Chem. 17, 149\u2013163 (1993).","journal-title":"Comput. Chem."},{"key":"10639_CR69","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1038\/nbt.3988","volume":"35","author":"M Steinegger","year":"2017","unstructured":"Steinegger, M. & S\u00f6ding, J. MMseqs2 enables sensitive protein sequence searching for the analysis of massive data sets. Nat. Biotechnol. 35, 1026\u20131028 (2017).","journal-title":"Nat. Biotechnol."},{"key":"10639_CR70","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1101\/gr.186072.114","volume":"25","author":"DH Parks","year":"2015","unstructured":"Parks, D. H., Imelfort, M., Skennerton, C. T., Hugenholtz, P. & Tyson, G. W. CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes. Genome Res. 25, 1043\u20131055 (2015).","journal-title":"Genome Res."},{"key":"10639_CR71","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1038\/s41396-020-0600-z","volume":"14","author":"OM Maistrenko","year":"2020","unstructured":"Maistrenko, O. M. et al. Disentangling the impact of environmental and phylogenetic constraints on prokaryotic within-species diversity. ISME J. 14, 1247\u20131259 (2020).","journal-title":"ISME J."},{"key":"10639_CR72","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1832-y","volume":"20","author":"DM Emms","year":"2019","unstructured":"Emms, D. M. & Kelly, S. OrthoFinder: phylogenetic orthology inference for comparative genomics. Genome Biol. 20, 238 (2019).","journal-title":"Genome Biol."},{"key":"10639_CR73","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","volume":"215","author":"SF Altschul","year":"1990","unstructured":"Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 215, 403\u2013410 (1990).","journal-title":"J. Mol. Biol."},{"key":"10639_CR74","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04964-5","volume":"9","author":"M Steinegger","year":"2018","unstructured":"Steinegger, M. & S\u00f6ding, J. Clustering huge protein sequence sets in linear time. Nat. Commun. 9, 2542 (2018).","journal-title":"Nat. Commun."},{"key":"10639_CR75","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/s41592-021-01101-x","volume":"18","author":"B Buchfink","year":"2021","unstructured":"Buchfink, B., Reuter, K. & Drost, H.-G. Sensitive protein alignments at tree-of-life scale using DIAMOND. Nat. Methods 18, 366\u2013368 (2021).","journal-title":"Nat. Methods"},{"key":"10639_CR76","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1093\/molbev\/mst010","volume":"30","author":"K Katoh","year":"2013","unstructured":"Katoh, K. & Standley, D. M. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol. Biol. Evol. 30, 772\u2013780 (2013).","journal-title":"Mol. Biol. Evol."},{"key":"10639_CR77","first-page":"205","volume":"23","author":"SR Eddy","year":"2009","unstructured":"Eddy, S. R. A new generation of homology search tools based on probabilistic inference. Genome Inform. 23, 205\u2013211 (2009).","journal-title":"Genome Inform."},{"key":"10639_CR78","doi-asserted-by":"publisher","first-page":"D1062","DOI":"10.1093\/nar\/gkab966","volume":"50","author":"D Fuentes","year":"2022","unstructured":"Fuentes, D. et al. PhylomeDB V5: an expanding repository for genome-wide catalogues of annotated gene phylogenies. Nucleic Acids Res. 50, D1062\u2013D1068 (2022).","journal-title":"Nucleic Acids Res."},{"key":"10639_CR79","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/1471-2105-13-117","volume":"13","author":"PW Collingridge","year":"2012","unstructured":"Collingridge, P. W. & Kelly, S. MergeAlign: improving multiple sequence alignment performance by dynamic reconstruction of consensus multiple sequence alignments. BMC Bioinformatics 13, 117 (2012).","journal-title":"BMC Bioinformatics"},{"key":"10639_CR80","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34630-w","volume":"13","author":"RC Edgar","year":"2022","unstructured":"Edgar, R. C. Muscle5: high-accuracy alignment ensembles enable unbiased assessments of sequence homology and phylogeny. Nat. Commun. 13, 6968 (2022).","journal-title":"Nat. Commun."},{"key":"10639_CR81","doi-asserted-by":"publisher","first-page":"1928","DOI":"10.1093\/bioinformatics\/btz795","volume":"36","author":"T Lassmann","year":"2019","unstructured":"Lassmann, T. Kalign 3: multiple sequence alignment of large datasets. Bioinformatics 36, 1928\u20131929 (2019).","journal-title":"Bioinformatics"},{"key":"10639_CR82","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1093\/bioinformatics\/btp348","volume":"25","author":"S Capella-Guti\u00e9rrez","year":"2009","unstructured":"Capella-Guti\u00e9rrez, S., Silla-Mart\u00ednez, J. M. & Gabald\u00f3n, T. trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics 25, 1972\u20131973 (2009).","journal-title":"Bioinformatics"},{"key":"10639_CR83","doi-asserted-by":"crossref","unstructured":"Wong, T. K. F. et al. IQ-TREE 3: phylogenomic inference software using complex evolutionary models. Mol. Biol. Evol. 43, msag117 (2026).","DOI":"10.1093\/molbev\/msag117"},{"key":"10639_CR84","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1093\/molbev\/msi005","volume":"22","author":"C Kosiol","year":"2005","unstructured":"Kosiol, C. & Goldman, N. Different versions of the Dayhoff rate matrix. Mol. Biol. Evol. 22, 193\u2013199 (2005).","journal-title":"Mol. Biol. Evol."},{"key":"10639_CR85","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1089\/10665270050514918","volume":"7","author":"T M\u00fcller","year":"2000","unstructured":"M\u00fcller, T. & Vingron, M. Modeling amino acid replacement. J. Comput. Biol. 7, 761\u2013776 (2000).","journal-title":"J. Comput. Biol."},{"key":"10639_CR86","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1093\/oxfordjournals.molbev.a003851","volume":"18","author":"S Whelan","year":"2001","unstructured":"Whelan, S. & Goldman, N. A general empirical model of protein evolution derived from multiple protein families using a maximum-likelihood approach. Mol. Biol. Evol. 18, 691\u2013699 (2001).","journal-title":"Mol. Biol. Evol."},{"key":"10639_CR87","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1093\/molbev\/msn067","volume":"25","author":"SQ Le","year":"2008","unstructured":"Le, S. Q. & Gascuel, O. An improved general amino acid replacement matrix. Mol. Biol. Evol. 25, 1307\u20131320 (2008).","journal-title":"Mol. Biol. Evol."},{"key":"10639_CR88","doi-asserted-by":"publisher","first-page":"2921","DOI":"10.1093\/molbev\/mss112","volume":"29","author":"SQ Le","year":"2012","unstructured":"Le, S. Q., Dang, C. C. & Gascuel, O. Modeling protein evolution with several amino acid replacement matrices depending on site rates. Mol. Biol. Evol. 29, 2921\u20132936 (2012).","journal-title":"Mol. Biol. Evol."},{"key":"10639_CR89","doi-asserted-by":"publisher","first-page":"2317","DOI":"10.1093\/bioinformatics\/btn445","volume":"24","author":"LS Quang","year":"2008","unstructured":"Quang, L. S., Gascuel, O. & Lartillot, N. Empirical profile mixture models for phylogenetic reconstruction. Bioinformatics 24, 2317\u20132323 (2008).","journal-title":"Bioinformatics"},{"key":"10639_CR90","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1093\/molbev\/msx281","volume":"35","author":"DT Hoang","year":"2018","unstructured":"Hoang, D. T., Chernomor, O., von Haeseler, A., Minh, B. Q. & Vinh, L. S. UFBoot2: improving the ultrafast bootstrap approximation. Mol. Biol. Evol. 35, 518\u2013522 (2018).","journal-title":"Mol. Biol. Evol."},{"key":"10639_CR91","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1093\/oxfordjournals.molbev.a026201","volume":"16","author":"H Shimodaira","year":"1999","unstructured":"Shimodaira, H. & Hasegawa, M. Multiple comparisons of log-likelihoods with applications to phylogenetic inference. Mol. Biol. Evol. 16, 1114\u20131116 (1999).","journal-title":"Mol. Biol. Evol."},{"key":"10639_CR92","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1093\/bioinformatics\/btz859","volume":"36","author":"T Aramaki","year":"2020","unstructured":"Aramaki, T. et al. KofamKOALA: KEGG Ortholog assignment based on profile HMM and adaptive score threshold. Bioinformatics 36, 2251\u20132252 (2020).","journal-title":"Bioinformatics"},{"key":"10639_CR93","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1093\/nar\/28.1.33","volume":"28","author":"RL Tatusov","year":"2000","unstructured":"Tatusov, R. L., Galperin, M. Y., Natale, D. A. & Koonin, E. V. The COG database: a tool for genome-scale analysis of protein functions and evolution. Nucleic Acids Res. 28, 33\u201336 (2000).","journal-title":"Nucleic Acids Res."},{"key":"10639_CR94","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41564-020-00834-3","volume":"6","author":"AM Eren","year":"2021","unstructured":"Eren, A. M. et al. Community-led, integrated, reproducible multi-omics with anvi\u2019o. Nat. Microbiol. 6, 3\u20136 (2021).","journal-title":"Nat. Microbiol."},{"key":"10639_CR95","doi-asserted-by":"crossref","unstructured":"Sato, N., Uematsu, M., Fujimoto, K., Uematsu, S. & Imoto, S. ggkegg: analysis and visualization of KEGG data utilizing the grammar of graphics. Bioinformatics 39, btad622 (2023).","DOI":"10.1093\/bioinformatics\/btad622"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41586-026-10639-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-026-10639-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-026-10639-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:03:51Z","timestamp":1786532631000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-026-10639-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,10]]},"references-count":95,"journal-issue":{"issue":"8127","published-print":{"date-parts":[[2026,8,13]]}},"alternative-id":["10639"],"URL":"https:\/\/doi.org\/10.1038\/s41586-026-10639-9","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,10]]},"assertion":[{"value":"19 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}