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Darwinian evolution of an alternative genetic system provides support for TNA as an RNA progenitor


The pre-RNA world hypothesis postulates that RNA was preceded in the evolution of life by a simpler genetic material, but it is not known if such systems can fold into structures capable of eliciting a desired function. Presumably, whatever chemistry gave rise to RNA would have produced other RNA analogues, some of which may have preceded or competed directly with RNA. Threose nucleic acid (TNA), a potentially natural derivative of RNA, has received considerable interest as a possible RNA progenitor due to its chemical simplicity and ability to exchange genetic information with itself and RNA. Here, we have applied Darwinian evolution methods to evolve, in vitro, a TNA receptor that binds to an arbitrary target with high affinity and specificity. This demonstration shows that TNA has the ability to fold into tertiary structures with sophisticated chemical functions, which provides evidence that TNA could have served as an ancestral genetic system during an early stage of life.

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Figure 1: Structure of TNA.
Figure 2: Synthesis of TNA libraries by enzyme-mediated primer extension.
Figure 3: Evolution of TNA receptors in vitro.


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The authors thank members of the Chaput laboratory for helpful comments and suggestions. This work was supported by start-up funds from the Biodesign Institute at Arizona State University.

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Authors and Affiliations



J.C. conceived the project and wrote the manuscript. H.Y., S.Z. and J.C. designed the experiments. H.Y. and S.Z. performed the experiments and wrote initial drafts of the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to John C. Chaput.

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The authors declare no competing financial interests.

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Yu, H., Zhang, S. & Chaput, J. Darwinian evolution of an alternative genetic system provides support for TNA as an RNA progenitor. Nature Chem 4, 183–187 (2012).

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