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A viscous solvent enables information transfer from gene-length nucleic acids in a model prebiotic replication cycle

Abstract

Many hypotheses concerning the nature of early life assume that genetic information was once transferred through the template-directed synthesis of RNA, before the emergence of coded enzymes. However, attempts to demonstrate enzyme-free, template-directed synthesis of nucleic acids have been limited by ‘strand inhibition’, whereby transferring information from a template strand in the presence of its complementary strand is inhibited by the stability of the template duplex. Here, we use solvent viscosity to circumvent strand inhibition, demonstrating information transfer from a gene-length template (>300 nt) within a longer (545 bp or 3 kb) duplex. These results suggest that viscous environments on the prebiotic Earth, generated periodically by water evaporation, could have facilitated nucleic acid replication—particularly of long, structured sequences such as ribozymes. Our approach works with DNA and RNA, suggesting that viscosity-mediated replication is possible for a range of genetic polymers, perhaps even for informational polymers that may have preceded RNA.

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Figure 1: Schematic representation of the strand inhibition problem and a possible solution using a viscous solvent.
Figure 2: Comparison of duplex formation kinetics in glycholine and in aqueous buffer.
Figure 3: Kinetics of oligonucleotide binding to a denatured 3 kb DNA duplex.
Figure 4: Viscosity-enabled gene-length information transfer from a 3 kb duplex.
Figure 5: Viscosity-enabled information transfer from 545 bp DNA and RNA duplexes.

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Acknowledgements

The authors thank V. Breedveld for viscosity measurements, G. Newnam for technical assistance and C. Cameron for helping to troubleshoot the work with RNA. This work was supported by the National Science Foundation (NSF) and the NASA Astrobiology Program under the NASA/NSF Center for Chemical Evolution (CHE-1504217). This work was jointly supported by a McDonnell Foundation 21st Century Science Initiative Grant on Studying Complex Systems no. 220020271. This material is based on work supported by the National Science Foundation Graduate Research Fellowship (C.H.) under grant no. DGE-1148903.

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All authors conceived and designed experiments. C.H., B.L. and I.G. performed experiments. C.H., I.G., M.A.G, and N.V.H. analysed the data and wrote the paper.

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Correspondence to Nicholas V. Hud.

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He, C., Gállego, I., Laughlin, B. et al. A viscous solvent enables information transfer from gene-length nucleic acids in a model prebiotic replication cycle. Nature Chem 9, 318–324 (2017). https://doi.org/10.1038/nchem.2628

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