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Sustainable replication and coevolution of cooperative RNAs in an artificial cell-like system

Nature Ecology & Evolution volume 2, pages 1654–1660 (2018)Cite this article

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Abstract

Cooperation among independently replicating molecules is a key phenomenon that allowed the development of complexity during the early evolution of life. Generally, this process is vulnerable to parasitic or selfish entities, which can easily appear and destroy such cooperation. It remains unclear how this fragile cooperation process appeared and has been sustained through evolution. Theoretical studies have indicated that spatial structures, such as compartments, allow sustainable replication and the evolution of cooperative replication, although this has yet to be confirmed experimentally. In this study, we constructed a molecular cooperative replication system, in which two types of RNA, encoding replication or metabolic enzymes, cooperate for their replication in compartments, and we performed long-term replication experiments to examine the sustainability and evolution of the RNAs. We demonstrate that the cooperative relationship of the two RNAs could be sustained at a certain range of RNA concentrations, even when parasitic RNA appeared in the system. We also found that more efficient cooperative RNA replication evolved during long-term replication through seemingly selfish evolution of each RNA. Our results provide experimental evidence supporting the sustainability and robustness of molecular cooperation on an evolutionary timescale.

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Fig. 1: Computer simulation of cooperative RNA replication.
Fig. 2: TcCRR system.
Fig. 3: Long-term replication experiments.
Fig. 4: Template and cooperation activity of the RNA clones in the replicating population.
Fig. 5: Cooperative replication assay of the evolved RNAs.

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References

  1. Maynard-Smith, J. & Szathmáry, E. The Major Transitions in Evolution (Oxford Univ. Press, Oxford, 1997).

  2. Nowak, M. A. Five rules for the evolution of cooperation. Science 314, 1560–1563 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Eigen, M. & Schuster, P. A principle of natural self-organization ‒ Part A: Emergence of the hypercycle. Naturwissenschaften 64, 541–565 (1977).

    Article  CAS  PubMed  Google Scholar 

  4. Niesert, U., Harnasch, D. & Bresch, C. Origin of life between Scylla and Charybdis. J. Mol. Evol. 17, 348–353 (1981).

    Article  CAS  PubMed  Google Scholar 

  5. Higgs, P. G. & Lehman, N. The RNA world: molecular cooperation at the origins of life. Nat. Rev. Genet. 16, 7–17 (2014).

    Article  CAS  PubMed  Google Scholar 

  6. Maynard Smith, J. Hypercycles and the origin of life. Nature 280, 445–446 (1979).

    Article  Google Scholar 

  7. Szathmary, E. & Demeter, L. Group selection of early replicators and the origin of life. J. Theor. Biol. 128, 463–486 (1987).

    Article  CAS  PubMed  Google Scholar 

  8. Boerlijst, M. C. & Hogeweg, P. Spiral wave structure in pre-biotic evolution – hypercycles stable against parasites. Physica D 48, 17–28 (1991).

    Article  Google Scholar 

  9. Hogeweg, P. Multilevel evolution – replicators and the evolution of diversity. Physica D 75, 275–291 (1994).

    Article  Google Scholar 

  10. McCaskill, J. S., Fuchslin, R. M. & Altmeyer, S. The stochastic evolution of catalysts in spatially resolved molecular systems. Biol. Chem. 382, 1343–1363 (2001).

    Article  CAS  PubMed  Google Scholar 

  11. Hogeweg, P. & Takeuchi, N. Multilevel selection in models of prebiotic evolution: compartments and spatial self-organization. Orig. Life Evol. Biosph. 33, 375–403 (2003).

    Article  CAS  PubMed  Google Scholar 

  12. Takeuchi, N. & Hogeweg, P. The role of complex formation and deleterious mutations for the stability of RNA-like replicator systems. J. Mol. Evol. 65, 668–686 (2007).

    Article  CAS  PubMed  Google Scholar 

  13. Branciamore, S., Gallori, E., Szathmary, E. & Czaran, T. The origin of life: chemical evolution of a metabolic system in a mineral honeycomb? J. Mol. Evol. 69, 458–469 (2009).

    Article  CAS  PubMed  Google Scholar 

  14. Takeuchi, N. & Hogeweg, P. Multilevel selection in models of prebiotic evolution II: a direct comparison of compartmentalization and spatial self-organization. PLoS Comput. Biol. 5, e1000542 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Frank, S. A. The origin of synergistic symbiosis. J. Theoret. Biol. 176, 403–410 (1995).

    Article  CAS  Google Scholar 

  16. Szabo, P., Scheuring, I., Czaran, T. & Szathmary, E. In silico simulations reveal that replicators with limited dispersal evolve towards higher efficiency and fidelity. Nature 420, 340–343 (2002).

    Article  CAS  PubMed  Google Scholar 

  17. Zintzaras, E., Santos, M. & Szathmáry, E. Selfishness versus functional cooperation in a stochastic protocell model. J. Theoret. Biol. 267, 605–613 (2010).

    Article  Google Scholar 

  18. Attolini, C. S. O. & Stadler, P. F. Evolving towards the hypercycle: a spatial model of molecular evolution. Physica D 217, 134–141 (2006).

    Article  Google Scholar 

  19. Lincoln, T. A. & Joyce, G. F. Self-sustained replication of an RNA enzyme. Science 323, 1229–1232 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Vaidya, N. et al. Spontaneous network formation among cooperative RNA replicators. Nature 491, 72–77 (2012).

    Article  CAS  PubMed  Google Scholar 

  21. Sievers, D. & von Kiedrowski, G. Self-replication of complementary nucleotide-based oligomers. Nature 369, 221–224 (1994).

    Article  CAS  PubMed  Google Scholar 

  22. Ellinger, T., Ehricht, R. & McCaskill, J. S. In vitro evolution of molecular cooperation in CATCH, a cooperatively coupled amplification system. Chem. Biol. 5, 729–741 (1998).

    Article  CAS  PubMed  Google Scholar 

  23. Lee, D. H., Severin, K., Yokobayashi, Y. & Ghadiri, M. R. Emergence of symbiosis in peptide self-replication through a hypercyclic network. Nature 390, 591–594 (1997).

    Article  CAS  PubMed  Google Scholar 

  24. Ichihashi, N. et al. Darwinian evolution in a translation-coupled RNA replication system within a cell-like compartment. Nat. Commun. 4, 2494 (2013).

    Article  CAS  PubMed  Google Scholar 

  25. Ichihashi, N., Aita, T., Motooka, D., Nakamura, S. & Yomo, T. Periodic pattern of genetic and fitness diversity during evolution of an artificial cell-like system. Mol. Biol. Evol. 32, 3205–3214 (2015).

    CAS  PubMed  Google Scholar 

  26. Bansho, Y., Furubayashi, T., Ichihashi, N. & Yomo, T. Host-parasite oscillation dynamics and evolution in a compartmentalized RNA replication system. Proc. Natl Acad. Sci. USA 113, 4045–4050 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bansho, Y. et al. Importance of parasite RNA species repression for prolonged translation-coupled RNA self-replication. Chem. Biol. 19, 478–487 (2012).

    Article  CAS  PubMed  Google Scholar 

  28. Monnard, P. A. & Walde, P. Current ideas about prebiological compartmentalization. Life 5, 1239–1263 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Niesert, U. How many genes to start with? A computer simulation about the origin of life. Origins Life Evol. B 17, 155–169 (1987).

    Article  CAS  Google Scholar 

  30. Palmenberg, A. & Kaesberg, P. Synthesis of complementary strands of heterologous RNAs with Qbeta replicase. Proc. Natl Acad. Sci. USA 71, 1371–1375 (1974).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Feix, G. Primer-dependent copying of rabbit globin mRNA with Qbeta replicase. Nature 259, 593–594 (1976).

    Article  CAS  PubMed  Google Scholar 

  32. Usui, K., Ichihashi, N. & Yomo, T. A design principle for a single-stranded RNA genome that replicates with less double-strand formation. Nucl. Acids Res. 43, 8033–8043 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Garcia-Villada, L. & Drake, J. W. The three faces of riboviral spontaneous mutation: spectrum, mode of genome replication, and mutation rate. PLoS Genet. 8, e1002832 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Eigen, M., Mccaskill, J. & Schuster, P. Molecular quasi-species. J. Phys. Chem. 92, 6881–6891 (1988).

    Article  CAS  Google Scholar 

  35. Mizuuchi, R., Ichihashi, N., Usui, K., Kazuta, Y. & Yomo, T. Adaptive evolution of an artificial RNA genome to a reduced ribosome environment. ACS Synth. Biol. 4, 292–298 (2015).

    Article  CAS  PubMed  Google Scholar 

  36. Shimizu, Y. et al. Cell-free translation reconstituted with purified components. Nat. Biotechnol. 19, 751–755 (2001).

    Article  CAS  PubMed  Google Scholar 

  37. Yumura, M. et al. Combinatorial selection for replicable RNA by Qbeta replicase while maintaining encoded gene function. PLoS ONE 12, e0174130 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mizuuchi, R., Ichihashi, N. & Yomo, T. Adaptation and diversification of an RNA replication system under initiation- or termination-impaired translational conditions. ChemBioChem 17, 1229–1232 (2016).

    Article  CAS  PubMed  Google Scholar 

  39. Kazuta, Y., Matsuura, T., Ichihashi, N. & Yomo, T. Synthesis of milligram quantities of proteins using a reconstituted in vitro protein synthesis system. J. Biosci. Bioeng. 118, 554–557 (2014).

    Article  CAS  PubMed  Google Scholar 

  40. Hosoda, K. et al. Kinetic analysis of the entire RNA amplification process by Qβ replicase. J. Biol. Chem. 282, 15516–15527 (2007).

    Article  CAS  PubMed  Google Scholar 

  41. Ichihashi, N., Matsuura, T., Hosoda, K. & Yomo, T. Identification of two forms of Q{beta} replicase with different thermal stabilities but identical RNA replication activity. J. Biol. Chem. 285, 37210–37217 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Lorenz, R. et al. ViennaRNA package 2.0. Algor. Mol. Biol. 6, 26 (2011).

    Article  Google Scholar 

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Acknowledgements

We would like to thank N. Lehman, N. Takeuchi and T. Yomo for useful discussion and comments. This work was supported by JSPS KAKENHI grant numbers JP15KT0080 and JP15H04407.

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Authors and Affiliations

  1. Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Osaka, Japan

    Ryo Mizuuchi & Norikazu Ichihashi

  2. Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan

    Norikazu Ichihashi

Authors
  1. Ryo Mizuuchi
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Contributions

R.M. designed and performed all experiments and wrote the manuscript. N.I. designed experiments and wrote the manuscript.

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Correspondence to Norikazu Ichihashi.

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Supplementary Discussion; Supplementary Figures 1–9; Supplementary Tables 1–5; Supplementary References

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Mizuuchi, R., Ichihashi, N. Sustainable replication and coevolution of cooperative RNAs in an artificial cell-like system. Nat Ecol Evol 2, 1654–1660 (2018). https://doi.org/10.1038/s41559-018-0650-z

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