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Selective prebiotic formation of RNA pyrimidine and DNA purine nucleosides
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The nature of the first genetic polymer is the subject of major debate 1. Although the 'RNA world' theory suggests that RNA was the first replicable information carrier of the prebiotic era-that is, prior to the dawn of life 2,3-other evidence implies that life may have started with a heterogeneous nucleic acid genetic system that included both RNA and DNA 4. Such a theory streamlines the eventual 'genetic takeover' of homogeneous DNA from RNA as the principal information-storage molecule, but requires a selective abiotic synthesis of both RNA and DNA building blocks in the same local primordial geochemical scenario. Here we demonstrate a high-yielding, completely stereo-, regio- and furanosyl-selective prebiotic synthesis of the purine deoxyribonucleosides: deoxyadenosine and deoxyinosine. Our synthesis uses key intermediates in the prebiotic synthesis of the canonical pyrimidine ribonucleosides (cytidine and uridine), and we show that, once generated, the pyrimidines persist throughout the synthesis of the purine deoxyribonucleosides, leading to a mixture of deoxyadenosine, deoxyinosine, cytidine and uridine. These results support the notion that purine deoxyribonucleosides and pyrimidine ribonucleosides may have coexisted before the emergence of life 5.
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“However, the search for a prebiotically plausible mechanism that can both induce and amplify a chiral bias in an RNA precursor from a fully racemic starting material has remained to be an open problem.”
From Origin of biological homochirality by crystallization of an RNA precursor on a magnetic surface (2023) · cites this paper as [26]
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“Follow-up studies highlighted ribo-aminooxazoline (RAO) as a key compound to resolve the origin of homochirality due to its centrality in the synthesis of nucleotides and crystallization properties (22, 25–27).”
From Origin of biological homochirality by crystallization of an RNA precursor on a magnetic surface (2023) · cites this paper as [26]
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“Glyceraldehyde is also the starting product in a sequence of reactions that produce through intermediates 15–18 both purine and pyrimidine (deoxy)ribonucleosides”
From The protometabolic nature of prebiotic chemistry (2023) · cites this paper as [103]
Experimental — accuracy not yet measuredIn the citing paper
“In a recent publication, this pathway was further elaborated to include the synthesis of purine deoxyribonucleosides [110].”
From Prebiotic Reaction Networks in Water (2020) · cites this paper as [110]
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Metadata
- Authors
- Xu, J., Chmela, V., Green, N. J., Russell, D. A., Janicki, M. J., Góra, R. W., Szabla, R., Bond, A. D., & Sutherland, J. D.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Wrocław University of Science and Technology (PL)
- Institute of Physics (PL)
- University of Cambridge (GB)
- Corresponding author
- Sutherland, John D.
- ORCID
- Venue
- Nature
- Published
- 2020-06-03
- Volume
- 582
- Issue
- 7810
- Pages
- 60-66
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7116818
- OpenAlex
- W3029443600
- Cited by
- 176
- References
- 50
- Citations by year
- 2026: 15 · 2025: 26 · 2024: 33 · 2023: 23 · 2022: 26 · 2021: 35 · 2020: 18
- FWCI
- 11.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Medical Research Council (MC UP A024 1009)
- Wroclawskie Centrum Sieciowo-Superkomputerowe, Politechnika Wroclawska
- Topics
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- prebiotic synthesis, RNA world, origin of life, deoxyadenosine, deoxyinosine, cytidine, uridine, stereo- and regioselectivity
- MeSH terms
- Origin of Life, Adenosine, Cytidine, DNA, Oxidation-Reduction, Purine Nucleosides, Pyrimidine Nucleosides, RNA, Uridine, Evolution, Chemical
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