Article | Published:

Spontaneous network formation among cooperative RNA replicators

Nature volume 491, pages 7277 (01 November 2012) | Download Citation

Abstract

The origins of life on Earth required the establishment of self-replicating chemical systems capable of maintaining and evolving biological information. In an RNA world, single self-replicating RNAs would have faced the extreme challenge of possessing a mutation rate low enough both to sustain their own information and to compete successfully against molecular parasites with limited evolvability. Thus theoretical analyses suggest that networks of interacting molecules were more likely to develop and sustain life-like behaviour. Here we show that mixtures of RNA fragments that self-assemble into self-replicating ribozymes spontaneously form cooperative catalytic cycles and networks. We find that a specific three-membered network has highly cooperative growth dynamics. When such cooperative networks are competed directly against selfish autocatalytic cycles, the former grow faster, indicating an intrinsic ability of RNA populations to evolve greater complexity through cooperation. We can observe the evolvability of networks through in vitro selection. Our experiments highlight the advantages of cooperative behaviour even at the molecular stages of nascent life.

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Change history

  • Corrected online 31 October 2012

    A minor typo in Fig. 1 was corrected.

References

  1. 1.

    RNA evolution and the origins of life. Nature 338, 217–224 (1989)

  2. 2.

    & Selection of an improved RNA polymerase ribozyme with superior extension and fidelity. RNA 13, 1017–1026 (2007)

  3. 3.

    , , & Ribozyme-catalyzed transcription of an active ribozyme. Science 332, 209–212 (2011)

  4. 4.

    & The hypercycle. A principle of natural self-organization. Part A: emergence of the hypercycle. Naturwissenschaften 64, 541–565 (1977)

  5. 5.

    The Origins of Order: Self-Organization and Selection in Evolution (Oxford Univ. Press, 1993)

  6. 6.

    & Self-replication of complementary nucleotide-based oligomers. Nature 369, 221–224 (1994)

  7. 7.

    & The descent of polymerization. Nature Struct. Biol. 8, 580–582 (2001)

  8. 8.

    The origin of replicators and reproducers. Phil. Trans. Royal Soc. B 361, 1761–1776 (2006)

  9. 9.

    & Preevolutionary dynamics and the origin of evolution. Proc. Natl Acad. Sci. USA 105, 14924–14927 (2008)

  10. 10.

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

  11. 11.

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

  12. 12.

    , & Real ribozymes suggest a relaxed error threshold. Nature Genet. 37, 1008–1011 (2005)

  13. 13.

    & RNA-catalysed synthesis of complementary-strand RNA. Nature 339, 519–522 (1989)

  14. 14.

    Forty years of in vitro evolution. Angew. Chem. Int. Ed. 46, 6420–6436 (2007)

  15. 15.

    & Self-sustained replication of an RNA enzyme. Science 323, 1229–1232 (2009)

  16. 16.

    & Exponential growth by cross-catalytic cleavage of deoxyribozymogens. Proc. Natl Acad. Sci. USA 100, 6416–6421 (2003)

  17. 17.

    , , & Emergence of symbiosis in peptide self-replication through a hypercyclic network. Nature 390, 591–594 (1997)

  18. 18.

    , & Autocatalytic networks: the transition from molecular self-replication to molecular ecosystems. Curr. Opin. Chem. Biol. 1, 491–496 (1997)

  19. 19.

    & Niche partitioning in the coevolution of 2 distinct RNA enzymes. Proc. Natl Acad. Sci. USA 106, 7780–7785 (2009)

  20. 20.

    & Cross-catalytic replication of an RNA ligase ribozyme. Chem. Biol. 11, 1505–1512 (2004)

  21. 21.

    & The hypercycle. A principle of natural self-organization. Part C: the realistic hypercycle. Naturwissenschaften 65, 341–369 (1978)

  22. 22.

    & Self-splicing introns in tRNA genes of widely divergent bacteria. Nature 357, 173–176 (1992)

  23. 23.

    & Self-assembly of a group I intron from inactive oligonucleotide fragments. Chem. Biol. 13, 909–918 (2006)

  24. 24.

    , & Systems chemistry on ribozyme self-construction: evidence for anabolic autocatalysis in a recombination network. Angew. Chem. Int. Ed. 47, 8424–8428 (2008)

  25. 25.

    , & Mechanisms of covalent self-assembly of the Azoarcus ribozyme from four fragment oligonucleotides. Nucleic Acids Res. 36, 520–531 (2008)

  26. 26.

    Evolutionary Dynamics: Exploring the Equations of Life (Harvard Univ. Press, 2006)

  27. 27.

    & Detecting autocatalytic, self-containing sets in chemical reaction systems. J. Theor. Biol. 227, 451–461 (2004)

  28. 28.

    & 3′ terminal tRNA-like structures tag genomic RNA molecules for replication: implications for the origin of protein synthesis. Proc. Natl Acad. Sci. USA 84, 7383–7387 (1987)

  29. 29.

    & Spiral wave structures in prebiotic evolution: hypercycles stable against parasites. Physica D 48, 17–28 (1991)

  30. 30.

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

  31. 31.

    , , & The mutational meltdown in asexual populations. J. Hered. 84, 339–344 (1993)

  32. 32.

    & The hypercycle. A principle of natural self-organization. Part B: the abstract hypercycle. Naturwissenschaften 65, 7–41 (1978)

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Acknowledgements

We would like to thank A. Burton, R. Ghadiri, P. Higgs, B. Larson, K. Chacón and A. López García de Lomana for help during preparation of this manuscript. This work was supported by NASA grant NNX10AR15G to N.L., the Center for Life in Extreme Environments at Portland State University, and a fellowship from the Human Frontier Science Program Organization to R.X.-B.

Author information

Author notes

    • Irene A. Chen

    Present address: Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, USA.

Affiliations

  1. Department of Chemistry, Portland State University, PO Box 751, Portland, Oregon 97207, USA

    • Nilesh Vaidya
    •  & Niles Lehman
  2. School of Engineering and Applied Sciences and Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138, USA

    • Michael L. Manapat
  3. FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138, USA

    • Irene A. Chen
    •  & Ramon Xulvi-Brunet
  4. Department of Bioengineering, Stanford University, Stanford, California 94305, USA

    • Eric J. Hayden

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Contributions

N.L. and N.V. conceived the basic idea and conducted the experiments; E.J.H. and I.A.C. contributed to the evaluation of the results; I.A.C., M.L.M. and R.X.-B. constructed the mathematical models; N.L. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Niles Lehman.

Supplementary information

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    Supplementary Information

    This file contains Supplementary Methods, Supplementary Text and Data, a Supplementary Discussion, Supplementary Figures 1-14, Supplementary Tables 1-3 and additional references.

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DOI

https://doi.org/10.1038/nature11549

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