Hypotheses of the origins of RNA and DNA are generally centred on the prebiotic synthesis of a pristine system (pre-RNA or RNA), which gives rise to its descendent. However, a lack of specificity in the synthesis of genetic polymers would probably result in chimeric sequences; the roles and fate of such sequences are unknown. Here, we show that chimeras, exemplified by mixed threose nucleic acid (TNA)–RNA and RNA–DNA oligonucleotides, preferentially bind to, and act as templates for, homogeneous TNA, RNA and DNA ligands. The chimeric templates can act as a catalyst that mediates the ligation of oligomers to give homogeneous backbone sequences, and the regeneration of the chimeric templates potentiates a scenario for a possible cross-catalytic cycle with amplification. This process provides a proof-of-principle demonstration of a heterogeneity-to-homogeneity scenario and also gives credence to the idea that DNA could appear concurrently with RNA, instead of being its later descendent.
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Full experimental details and data are provided in the Supplementary Information. The raw data that support the findings of this study are available from the corresponding author upon reasonable request.
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The work was supported by a grant from NASA (NNX14AP59G) and the Simons Foundation to R.K. (327124). S.B. thanks the NASA Astrobiology Postdoctoral Program for a fellowship. We thank the S. F. Dowdy laboratory for the use of their instrument for MALDI–TOF analysis. We thank J. Szostak, I. Chen, D. Braun, U. Muller, L. Leman, A. Lazcano and our lab members for helpful discussions.
The authors declare no competing interests.
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Supplementary information provides details of the synthesis and ligation of TNA–RNA and DNA–RNA chimeric oligonucleotide sequences, and of the stepwise dilution and cross-catalytic self-replication studies.
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Bhowmik, S., Krishnamurthy, R. The role of sugar-backbone heterogeneity and chimeras in the simultaneous emergence of RNA and DNA. Nat. Chem. 11, 1009–1018 (2019). https://doi.org/10.1038/s41557-019-0322-x
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