Diversification of self-replicating molecules


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.

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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.


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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).

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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.

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Correspondence to Sijbren Otto.

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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

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