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Spontaneous network formation among cooperative RNA replicators

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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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Figure 1: Cooperative covalent assembly of recombinase ribozymes.
Figure 2: Cooperative chemistry out-competes selfish chemistry when directly competed.
Figure 3: The randomization experiment.
Figure 4: The serial transfer experiment.
Figure 5: Growth curve of a four-piece system.

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Change history

  • 31 October 2012

    A minor typo in Fig. 1 was corrected.


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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.

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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.

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Correspondence to Niles Lehman.

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The authors declare no competing financial interests.

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This file contains Supplementary Methods, Supplementary Text and Data, a Supplementary Discussion, Supplementary Figures 1-14, Supplementary Tables 1-3 and additional references. (PDF 4848 kb)

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

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