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The Paradox of Dual Roles in the RNA World: Resolving the Conflict Between Stable Folding and Templating Ability

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Abstract

The hypothesized dual roles of RNA as both information carrier and biocatalyst during the earliest stages of life require a combination of features: good templating ability (for replication) and stable folding (for ribozymes). However, this poses the following paradox: well-folded sequences are poor templates for copying, but poorly folded sequences are unlikely to be good ribozymes. Here, we describe a strategy to overcome this dilemma through G:U wobble pairing in RNA. Unlike Watson–Crick base pairs, wobble pairs contribute highly to the energetic stability of the folded structure of their sequence, but only slightly, if at all, to the stability of the folded reverse complement. Sequences in the RNA World might thereby combine stable folding of the ribozyme with an unstructured, reverse-complementary genome, resulting in a “division of labor” between the strands. We demonstrate this strategy using computational simulations of RNA folding and an experimental model of early replication, nonenzymatic template-directed RNA primer extension. Additional study is needed to solve other problems associated with a complete replication cycle, including separation of strands after copying. Interestingly, viroid RNA sequences, which have been suggested to be relics of an RNA World (Diener, Proc Natl Acad Sci USA 86:9370–9374, 1989), also show significant asymmetry in folding energy between the infectious (+) and template (−) strands due to G:U pairing, suggesting that this strategy may even be used by replicators in the present day.

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Acknowledgments

The authors thank the anonymous reviewers and the editors for their comments. This work was supported by Grant 290356 from the Simons Foundation (I.A.C.), Grant RFP-12-05 from the Foundational Questions in Evolutionary Biology Fund of the John Templeton Foundation (I.A.C), a DAAD Grant (B.O.), DFG Grant GE 1098/3-1 (U.G.), and NIH Grant GM068763 to the Center for Modular Biology at Harvard. I.A.C. was a Bauer Fellow at Harvard University.

Conflict of interest

The authors declare that they have no conflict of interest.

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Author notes

  1. Benedikt Obermayer

    Present address: Max-Delbruck Center for Molecular Medicine, Berlin, Germany

Authors and Affiliations

  1. FAS Center for Systems Biology, Harvard University, Cambridge, MA, USA

    Nikola A. Ivica, Sudha Rajamani & Irene A. Chen

  2. Department of Physics, Harvard University, Cambridge, MA, USA

    Benedikt Obermayer

  3. Department of Physics, Ludwig-Maximillian University, Munich, Germany

    Ulrich Gerland

  4. Department of Chemistry and Biochemistry and Program in Biomolecular Sciences and Engineering, University of California, Santa Barbara, CA, USA

    Gregory W. Campbell & Irene A. Chen

Authors
  1. Nikola A. Ivica
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  2. Benedikt Obermayer
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  3. Gregory W. Campbell
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  4. Sudha Rajamani
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  5. Ulrich Gerland
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  6. Irene A. Chen
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Corresponding author

Correspondence to Irene A. Chen.

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Ivica, N.A., Obermayer, B., Campbell, G.W. et al. The Paradox of Dual Roles in the RNA World: Resolving the Conflict Between Stable Folding and Templating Ability. J Mol Evol 77, 55–63 (2013). https://doi.org/10.1007/s00239-013-9584-x

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  • DOI: https://doi.org/10.1007/s00239-013-9584-x

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