The Emergence of RNA from the Heterogeneous Products of Prebiotic Nucleotide Synthesis
Open accessAbstract
Recent advances in prebiotic chemistry are beginning to outline plausible pathways for the synthesis of the canonical ribonucleotides and their assembly into oligoribonucleotides. However, these reaction pathways suggest that many noncanonical nucleotides are likely to have been generated alongside the standard ribonucleotides. Thus, the oligomerization of prebiotically synthesized nucleotides is likely to have led to a highly heterogeneous collection of oligonucleotides comprised of a wide range of types of nucleotides connected by a variety of backbone linkages. How then did relatively homogeneous RNA emerge from this primordial heterogeneity? Here we focus on nonenzymatic template-directed primer extension as a process that would have strongly enriched for homogeneous RNA over the course of multiple cycles of replication. We review the effects on copying the kinetics of nucleotides with altered nucleobase and sugar moieties, when they are present as activated monomers and when they are incorporated into primer and template oligonucleotides. We also discuss three variations in backbone connectivity, all of which are nonheritable and regenerate native RNA upon being copied. The kinetic superiority of RNA synthesis suggests that nonenzymatic copying served as a chemical selection mechanism that allowed relatively homogeneous RNA to emerge from a complex mixture of prebiotically synthesized nucleotides and oligonucleotides.
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Szostak and co-workers found that 5′-5′imidazolium bridged dinucleotides improved fidelity and reaction rates by virtue of higher template-affinity and geometrical positioning of the reactive species.
“Szostak and co-workers found that 5′-5′imidazolium bridged dinucleotides, which are formed spontaneously in the nucleotide activation reaction, improved fidelity and reaction rates by virtue of higher template-affinity and geometrical positioning of the reactive species.12−14”
From Sequencing of <scp>d</scp>/<scp>l</scp>-DNA and XNA by Templated-Synthesis (2025) · cites this paper as [14]
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The protometabolic nature of prebiotic chemistry
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- Authors
- Kim, S. C., O’Flaherty, D. K., Giurgiu, C., Zhou, L., & Szostak, J. W.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Szostak, Jack W.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-02-26
- Volume
- 143
- Issue
- 9
- Pages
- 3267-3279
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W3130279262
- Cited by
- 55
- References
- 16
- Citations by year
- 2026: 14 · 2025: 10 · 2024: 8 · 2023: 10 · 2022: 11 · 2021: 2
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of the American Chemical Society (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Division of Chemistry (CHE-1607034)
- Howard Hughes Medical Institute
- Simons Foundation (290363)
- Fonds de Recherche du Quebec-Nature et Technologies
- Canadian Institutes of Health Research
- 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
- nucleotide activation, nucleobase modification, sugar modification, chemical selection
- MeSH terms
- Nucleotides, RNA, Templates, Genetic, Evolution, Molecular
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