Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Diversification of self-replicating molecules

Abstract

How new species emerge in nature is still incompletely understood and difficult to study directly. Self-replicating molecules provide a simple model that allows us to capture the fundamental processes that occur in species formation. We have been able to monitor in real time and at a molecular level the diversification of self-replicating molecules into two distinct sets that compete for two different building blocks (‘food’) and so capture an important aspect of the process by which species may arise. The results show that the second replicator set is a descendant of the first and that both sets are kinetic products that oppose the thermodynamic preference of the system. The sets occupy related but complementary food niches. As diversification into sets takes place on the timescale of weeks and can be investigated at the molecular level, this work opens up new opportunities for experimentally investigating the process through which species arise both in real time and with enhanced detail.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Library synthesis and the mechanism of self-replication.
Figure 2: Simplified kinetic profiles for the formation of sets I and II and distributions of the mutants.
Figure 3: Seeding of set II with different distributions of set I mutants.
Figure 4: Simplified kinetic profiles for the diversification and distributions of the mutants in a library seeded with octamer (2)8.
Figure 5: Replicator distribution on re-equilibration of the system.

Similar content being viewed by others

References

  1. Schluter, D. Ecology and the origin of species. Trends Ecol. Evol. 16, 372–380 (2001).

    Article  CAS  Google Scholar 

  2. Sobel, J. M., Chen, G. F., Watt, L. R. & Schemske, D. W. The biology of speciation. Evolution 64, 295–315 (2010).

    Article  Google Scholar 

  3. Hart, M. W. The species concept as an emergent property of population biology. Evolution 65, 613–616 (2011).

    Article  Google Scholar 

  4. Hey, J. On the failure of modern species concepts. Trends Ecol. Evol. 21, 447–450 (2006).

    Article  Google Scholar 

  5. Orgel, L. E. Molecular replication. Nature 358, 203–209 (1992).

    Article  CAS  Google Scholar 

  6. Wintner, E. A. & Rebek, J. Autocatalysis and the generation of self-replicating systems. Acta Chem. Scand. 50, 469–485 (1996).

    Article  CAS  Google Scholar 

  7. Lee, D. H., Severin, K. & Ghadiri, M. R. Autocatalytic networks: the transition from molecular self-replication to molecular ecosystems. Curr. Opin. Chem. Biol. 1, 491–496 (1997).

    Article  CAS  Google Scholar 

  8. Ghosh, I. & Chmielewski, J. Peptide self-assembly as a model of proteins in the pre-genomic world. Curr. Opin. Chem. Biol. 8, 640–644 (2004).

    Article  CAS  Google Scholar 

  9. Paul, N. & Joyce, G. F. Minimal self-replicating systems. Curr. Opin. Chem. Biol. 8, 634–639 (2004).

    Article  CAS  Google Scholar 

  10. Dadon, Z., Wagner, N. & Ashkenasy, G. The road to non-enzymatic molecular networks. Angew. Chem. Int. Ed. 47, 6128–6136 (2008).

    Article  CAS  Google Scholar 

  11. Vidonne, A. & Philp, D. Making molecules make themselves—the chemistry of artificial replicators. Eur. J. Org. Chem. 5, 593–610 (2009).

    Article  Google Scholar 

  12. Kassianidis, E., Pearson, R. J., Wood, E. A. & Philp, D. Designing instructable networks using synthetic replicators. Discuss. Faraday Soc. 145, 235–254 (2010).

    Article  CAS  Google Scholar 

  13. Bissette, A. J. & Fletcher, S. P. Mechanisms of autocatalysis. Angew. Chem. Int. Ed. 52, 12800–12826 (2013).

    Article  CAS  Google Scholar 

  14. Szathmáry, E. The evolution of replicators. Phil. Trans. R. Soc. Lond. B 355, 1669–1676 (2000).

    Article  Google Scholar 

  15. Eigen, M. Selforganization of matter and the evolution of biological macromolecules. Naturwissenschaften 58, 465–523 (1971).

    Article  CAS  Google Scholar 

  16. Eigen, M. & Schuster, P. The hypercycle. A principle of natural self-organisation. Part A: emergence of the hypercycle. Naturwissenschaften 64, 541–565 (1977).

    Article  CAS  Google Scholar 

  17. Domingo, E. & Perales, C. From quasi-species theory to viral quasi-species: how complexity has permeated virology. Math. Model. Nat. Phenom. 7, 105–122 (2012).

    Article  CAS  Google Scholar 

  18. Domingo, E., Sheldon, J. & Perales, C. Viral quasispecies evolution. Microbiol. Mol. Biol. Rev. 76, 159–216 (2012).

    Article  CAS  Google Scholar 

  19. Eigen, M. Steps toward Life: a Perspective on Evolution 79–87 (Oxford Univ. Press, 1992).

    Google Scholar 

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

    Article  CAS  Google Scholar 

  21. Nowak, M. A. What is a quasispecies? Trends Ecol. Evol. 7, 118–121 (1992).

    Article  CAS  Google Scholar 

  22. Bull, J. J., Meyers, L. A. & Lachmann, M. Quasispecies made simple. PLoS Comput. Biol. 6, e61 (2005).

    Article  Google Scholar 

  23. Ruiz-Mirazo, K., Briones, C. & de la Escosura, A. Prebiotic systems chemistry: new perspectives for the origins of life. Chem. Rev. 114, 285–366 (2014).

    Article  CAS  Google Scholar 

  24. Reek, J. N. H. & Otto, S. Dynamic Combinatorial Chemistry (Wiley-VCH, 2010).

    Book  Google Scholar 

  25. Cougnon, F. B. L. & Sanders, J. K. M. Evolution of dynamic combinatorial chemistry. Acc. Chem. Res. 45, 2211–2221 (2012).

    Article  CAS  Google Scholar 

  26. Otto, S. Dynamic molecular networks: from synthetic receptors to self-replicators. Acc. Chem. Res. 45, 2200–2210 (2012).

    Article  CAS  Google Scholar 

  27. Li, J., Nowak, P. & Otto, S. Dynamic combinatorial libraries: from exploring molecular recognition to systems chemistry. J. Am. Chem. Soc. 135, 9222–9239 (2013).

    Article  CAS  Google Scholar 

  28. Lehn, J. M. From supramolecular chemistry towards constitutional dynamic chemistry and adaptive chemistry. Chem. Soc. Rev. 36, 151–160 (2007).

    Article  CAS  Google Scholar 

  29. Corbett, P. T. et al. Dynamic combinatorial chemistry. Chem. Rev. 106, 3652–3711 (2006).

    Article  CAS  Google Scholar 

  30. Carnall, J. M. A. et al. Mechanosensitive self-replication driven by self-organization. Science 327, 1502–1506 (2010).

    Article  CAS  Google Scholar 

  31. Malakoutikhah, M. et al. Uncovering the selection criteria for the emergence of multi-building-block replicators from dynamic combinatorial libraries. J. Am. Chem. Soc. 135, 18406–18417 (2013).

    Article  CAS  Google Scholar 

  32. Moulin, E. & Giuseppone, N. Dynamic combinatorial self-replicating systems. Top. Curr. Chem. 322, 87–105 (2012).

    Article  CAS  Google Scholar 

  33. Ji, Q., Lirag, R. C. & Miljanić, O. Š. Kinetically controlled phenomena in dynamic combinatorial libraries. Chem. Soc. Rev. 43, 1873–1884 (2014).

    Article  CAS  Google Scholar 

  34. Xu, S. & Giuseppone, N. Self-duplicating amplification in a dynamic combinatorial library. J. Am. Chem. Soc. 130, 1826–1827 (2008).

    Article  CAS  Google Scholar 

  35. Sadownik, J. W. & Philp, D. A simple synthetic replicator amplifies itself from a dynamic reagent pool. Angew. Chem. Int. Ed. 47, 9965–9970 (2008).

    Article  CAS  Google Scholar 

  36. del Amo, V. & Philp, D. Integrating replication-based selection strategies in dynamic covalent systems. Chem. Eur. J. 16, 13304–13318 (2010).

    Article  CAS  Google Scholar 

  37. Otto, S., Furlan, R. L. E. & Sanders, J. K. M. Dynamic combinatorial libraries of macrocyclic disulfides in water. J. Am. Chem. Soc. 122, 12063–12064 (2000).

    Article  CAS  Google Scholar 

  38. Colomb-Delsuc, M., Mattia, E., Sadownik, J. W. & Otto, S. Exponential replication enabled through a fibre elongation/breakage mechanism. Nature Commun. 6, 7427 (2015).

    Article  CAS  Google Scholar 

  39. Pal, A. et al. Controlling the structure and length of self-synthesizing supramolecular polymers through nucleated growth and disassembly. Angew. Chem. Int. Ed. 54, 7852–7856 (2015).

    Article  CAS  Google Scholar 

  40. Pascal, R., Pross, A. & Sutherland, J. D. Towards an evolutionary theory of the origin of life based on kinetics and thermodynamics. Open Biol. 3, 130156 (2013).

    Article  Google Scholar 

Download references

Acknowledgements

We are grateful to F. Weissing and S. van Doorn for useful discussions and we acknowledge support from the European Research Council, The Netherlands Organization for Scientific Research, European Cooperation in Science and Technology CM1005 and CM1304, and the Dutch Ministry of Education, Culture and Science (Gravitation Program 024.001.035).

Author information

Authors and Affiliations

Authors

Contributions

J.W.S. conceived, designed and performed the experiments. E.M. and P.N. performed the UPLC-MS analysis. S.O. supervised the overall project. J.W.S., P.N. and S.O. co-wrote the paper. All the authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Sijbren Otto.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 3106 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sadownik, J., Mattia, E., Nowak, P. et al. Diversification of self-replicating molecules. Nature Chem 8, 264–269 (2016). https://doi.org/10.1038/nchem.2419

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.2419

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing