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Proposal of the reverse flow model for the origin of the eukaryotic cell based on comparative analyses of Asgard archaeal metabolism

Nature Microbiology volume 4, pages 1138–1148 (2019)Cite this article

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Abstract

The origin of eukaryotes represents an unresolved puzzle in evolutionary biology. Current research suggests that eukaryotes evolved from a merger between a host of archaeal descent and an alphaproteobacterial endosymbiont. The discovery of the Asgard archaea, a proposed archaeal superphylum that includes Lokiarchaeota, Thorarchaeota, Odinarchaeota and Heimdallarchaeota suggested to comprise the closest archaeal relatives of eukaryotes, has helped to elucidate the identity of the putative archaeal host. Whereas Lokiarchaeota are assumed to employ a hydrogen-dependent metabolism, little is known about the metabolic potential of other members of the Asgard superphylum. We infer the central metabolic pathways of Asgard archaea using comparative genomics and phylogenetics to be able to refine current models for the origin of eukaryotes. Our analyses indicate that Thorarchaeota and Lokiarchaeota encode proteins necessary for carbon fixation via the Wood–Ljungdahl pathway and for obtaining reducing equivalents from organic substrates. By contrast, Heimdallarchaeum LC2 and LC3 genomes encode enzymes potentially enabling the oxidation of organic substrates using nitrate or oxygen as electron acceptors. The gene repertoire of Heimdallarchaeum AB125 and Odinarchaeum indicates that these organisms can ferment organic substrates and conserve energy by coupling ferredoxin reoxidation to respiratory proton reduction. Altogether, our genome analyses suggest that Asgard representatives are primarily organoheterotrophs with variable capacity for hydrogen consumption and production. On this basis, we propose the ‘reverse flow model’, an updated symbiogenetic model for the origin of eukaryotes that involves electron or hydrogen flow from an organoheterotrophic archaeal host to a bacterial symbiont.

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Fig. 1: Metabolic potential of different Asgard phyla.
Fig. 2: Complex evolutionary history of group 3 and group 4 [NiFe]-hydrogenases in Asgard archaea.
Fig. 3: Evolution of the Asgard superphylum and selected metabolic features.
Fig. 4: Evolutionary scenarios for the origin of the eukaryotic cell.

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Code availability

The small custom scripts used for genome annotation and phylogenetic analyses are made available on figshare and can be accessed at the following link: https://figshare.com/s/5f153d1dcacadd3b3ed6.

Data availability

The genomes of the herein analysed Asgard archaea have been made publicly available on NCBI previously2,4. Detailed annotations of the metabolic repertoire are provided in Supplementary Tables 1–3 accompanying this paper. Raw data files are made available via figshare under the following link: https://figshare.com/s/5f153d1dcacadd3b3ed6.

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Acknowledgements

This work was supported by grants from the European Research Council (ERC starting grant 310039-PUZZLE_CELL to T.J.G.E.), the Swedish Foundation for Strategic Research (SSF-FFL5 to T.J.G.E.), the Swedish Research Council (VR grant 2015-04959 to T.J.G.E. and VR starting grant 2016-03559 to A.S.), the NWO-I Foundation of the Netherlands Organisation for Scientific Research (WISE fellowship to A.S.), the European Commission (Marie Curie IEF European grants 625521 to A.S. and 704263 to L.E.), the Wenner-Gren Foundations in Stockholm (2016-0072 to J.L.), the European Molecular Biology Organization (EMBO long-term fellowship ALTF-997–2015 to C.W.S.), the Natural Sciences and Engineering Research Council of Canada (C.W.S), the Australian Research Council (DE170100310 and DP180101762 to C.G.) and the National Science Foundation (DEB: Systematics and Biodiversity Sciences; award number 1737298 to B.J.B.). We thank K. Zaremba-Niedzwiedzka and J. Saw for reconstruction of some of these genomes and helpful discussions. We also acknowledge S. L. Jørgensen, the chief scientist R. B. Pedersen, the scientific party and the entire crew on board the Norwegian research vessel G.O. Sars during the summer 2010 expedition, which allowed us access to samples from Loki’s Castle. Finally, we thank P. Offre for discussions on metabolic inferences.

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Authors and Affiliations

  1. Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden

    Anja Spang, Courtney W. Stairs, Laura Eme, Jonathan Lombard, Eva F. Caceres & Thijs J. G. Ettema

  2. NIOZ, Royal Netherlands Institute for Sea Research, Department of Marine Microbiology and Biogeochemistry, and Utrecht University, AB Den Burg, The Netherlands

    Anja Spang & Nina Dombrowski

  3. Department of Marine Science, University of Texas at Austin, Marine Science Institute, Port Aransas, TX, USA

    Nina Dombrowski & Brett J. Baker

  4. School of Biological Sciences, Monash University, Clayton, Victoria, Australia

    Chris Greening

  5. Laboratory of Microbiology, Department of Agrotechnology and Food Sciences, Wageningen University, Wageningen, The Netherlands

    Thijs J. G. Ettema

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Contributions

A.S. and T.J.G.E. conceived the study. A.S., C.W.S., E.F.C., J.L., C.G., B.J.B. and N.D. analysed the genomic data. A.S., C.W.S. and L.E. performed the phylogenetic analyses. A.S. and T.J.G.E. wrote the manuscript with input from all authors. A.S., C.W.S. and N.D. wrote the Supplementary Information. All documents were edited and approved by all authors.

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Correspondence to Anja Spang or Thijs J. G. Ettema.

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Supplementary Information

Supplementary Text, Supplementary References, legends for Supplementary Tables, Supplementary Figures 1–18 and Supplementary Files 1–3.

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Supplementary Tables 1–4

Overview of the presence/absence of discussed enzymes in Asgard lineages; annotations for proteins, which serve as candidate enzymes potentially involved in the various metabolic pathways discussed throughout this manuscript; automatic annotation of all genes; carbohydrate active enzymes, peptidases, esterases and information on extracellular localization.

Supplementary Table 5

Annotation of beta-oxidation genes encoded by Asgard genomes per protein family/phylogeny.

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Spang, A., Stairs, C.W., Dombrowski, N. 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, 1138–1148 (2019). https://doi.org/10.1038/s41564-019-0406-9

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