Ice as a protocellular medium for RNA replication
Open accessAbstract
A crucial transition in the origin of life was the emergence of an informational polymer capable of self-replication and its compartmentalization within protocellular structures. We show that the physicochemical properties of ice, a simple medium widespread on a temperate early Earth, could have mediated this transition prior to the advent of membraneous protocells. Ice not only promotes the activity of an RNA polymerase ribozyme but also protects it from hydrolytic degradation, enabling the synthesis of exceptionally long replication products. Ice furthermore relieves the dependence of RNA replication on prebiotically implausible substrate concentrations, while providing quasicellular compartmentalization within the intricate microstructure of the eutectic phase. Eutectic ice phases had previously been shown to promote the de novo synthesis of nucleotide precursors, as well as the condensation of activated nucleotides into random RNA oligomers. Our results support a wider role for ice as a predisposed environment, promoting all the steps from prebiotic synthesis to the emergence of RNA self-replication and precellular Darwinian evolution.
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RPRs generally depend upon tethering to template due to their poor affinity for primer/template duplex.
“Due to their poor affinity for primer/template duplex (Lawrence and Bartel, 2003), RPRs generally depend upon such tethering to template (Attwater et al., 2010; Wochner et al., 2011; Horning and Joyce, 2016), which enhances local ribozyme concentration and promotes formation of the RPR-primer/template holoenzyme (Attwater et al., 2010; Attwater et al., 2013a).”
From Ribozyme-catalysed RNA synthesis using triplet building blocks (2018) · cites this paper as Attwater et al., 2010
The Figure 1 caption describes a polymerase ribozyme variant designed to hybridize to the template upstream of the primer, and the Polymerase assay section describes its matching capture template. These passages support tethering for the variant studied, but not the broader assertion that RPRs generally depend on tethering. The cited paper does not establish poor primer/template-duplex affinity as the reason; the citing sentence attributes that premise to a different source. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIce crystal formation upon eutectic phase equilibration concentrates all solutes approximately 4-5 fold to their final operational levels, and cooling elevates tris-buffered pH to approximately 9.2.
“Ice crystal formation upon eutectic phase equilibration, however, concentrates all solutes ~4–5 fold (Attwater et al., 2010) to their final operational levels and cooling elevates tris-buffered pH to ~9.2.”
From Ribozyme-catalysed RNA synthesis using triplet building blocks (2018) · cites this paper as Attwater et al., 2010
In “Freezing enables RNA replication from highly dilute solutions” (page unavailable), the paper explains that ice formation concentrates solutes in the eutectic phase. It estimates a greater than 200-fold enhancement for dilute starting reactions, but does not establish the cited ~4–5-fold figure or that it applies to all solutes. The citation is attached to the concentration claim, not the subsequent statement about pH. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn the authors' work, the process of cooperative binding and unfolding is aided by the cold temperature and solute concentration effects of eutectic ice phase formation.
“In our work, this process is aided by the cold temperature and solute concentration effects of eutectic ice phase formation (Attwater et al., 2010; Mutschler et al., 2015).”
From Ribozyme-catalysed RNA synthesis using triplet building blocks (2018) · cites this paper as Attwater et al., 2010
Y exceeded R18 by about fourfold at 17°C, by more than 15-fold at −7°C in ice, and by more than 30-fold in supercooled solution.
“While Y outperformed R18 by fourfold at 17°C (as judged by gel densitometry of average extension per primer15,22), at −7°C the differential rose to more than 15-fold in ice, and more than 30-fold in a supercooled solution.”
From In-ice evolution of RNA polymerase ribozyme activity (2013) · cites this paper as [15]
Ice can enhance polymerase ribozyme activity and stability even though R18 was evolved at 22°C and is poorly adapted to the low temperature of the ice phase.
“We had previously shown that ice, a biphasic medium, could enhance both polymerase ribozyme activity and stability15 - despite the poor adaptation of the R18 polymerase ribozyme (evolved at 22°C) to the low temperatures of the ice phase (−7°C).”
From In-ice evolution of RNA polymerase ribozyme activity (2013) · cites this paper as [15]
R18 is not capable of self-replication because its synthetic capacity is limited, partly by weak primer/template duplex binding, and because it is unstable in the high Mg2+ concentration needed for polymerase activity.
“However, the activity of R18 falls short of that required for self-replication in both its limited synthetic capacity (exacerbated by a low affinity for substrate primer/template duplex14) as well as its poor stability in the presence of the high concentration of Mg2+ ions (200 mM) required for polymerase activity9,15,16.”
From In-ice evolution of RNA polymerase ribozyme activity (2013) · cites this paper as [15]
Sanger sequencing of full-length products showed that the Y mutations gave a modest fidelity improvement, to 98.3% at 17°C versus 97.3% for tC19, and to 94.8% in ice versus 93.4% for R18.
“Sanger sequencing of full length products11 (Supplementary Table S2) indicated that the Y mutations conferred a modest fidelity improvement at 17°C to 98.3% compared to 97.3% for tC1911, and in ice to 94.8% compared to 93.4% for R1815.”
From In-ice evolution of RNA polymerase ribozyme activity (2013) · cites this paper as [15]
Icy cold conditions enhance synthetic RNA polymerase ribozyme activity and shield the macromolecule from hydrolysis.
“In the laboratory, cold conditions in icy environments promote the activity of synthetic RNA polymerase ribozymes, while also protecting the macromolecule from hydrolysis.”
From Environmental Adaptation from the Origin of Life to the Last Universal Common Ancestor (2018) · cites this paper as Attwater et al. 2010
At colder temperatures, better stabilization and less degradation of ribozymes offset slower polymerization, allowing very long molecules to form.
“While colder temperatures would slow down RNA polymerization rates, the enhanced stabilization and reduced degradation of the ribozyme counteract this effect, permitting synthesis of remarkably long molecules (Attwater et al. 2013;Attwater et al. 2010).”
From Environmental Adaptation from the Origin of Life to the Last Universal Common Ancestor (2018) · cites this paper as Attwater et al. 2010
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- Authors
- Attwater, J., Wochner, A., Pinheiro, V. B., Coulson, A., & Holliger, P.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Holliger, Philipp
- Venue
- Nature Communications
- Published
- 2010-09-21
- Volume
- 1
- Issue
- 1
- Pages
- 76-76
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2000597122
- Cited by
- 165
- References
- 53
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 20 · 2023: 7 · 2022: 8 · 2021: 13 · 2020: 13 · 2019: 15 · 2018: 14 · 2017: 12 · 2016: 6 · 2015: 8 · 2014: 5 · 2013: 7 · 2012: 7
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- BIROn (Birkbeck, University of London) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Medical Research Council
- 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 › Genetics › Evolution and Genetic Dynamics
- Keywords
- origin of life, RNA self-replication, ice, protocells, compartmentalization, prebiotic synthesis, early Earth, nucleotide precursors
- MeSH terms
- Ice, Microscopy, Electron, Scanning, RNA, RNA, Catalytic, Artificial Cells
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