The paradox of dual roles in the RNA world: resolving the conflict between stable folding and templating ability
Open accessAbstract
The hypothesized dual roles of RNA as both information carrier and biocatalyst during the earliest stages of life require a combination of features: good templating ability (for replication) and stable folding (for ribozymes). However, this poses the following paradox: well-folded sequences are poor templates for copying, but poorly folded sequences are unlikely to be good ribozymes. Here, we describe a strategy to overcome this dilemma through G:U wobble pairing in RNA. Unlike Watson-Crick base pairs, wobble pairs contribute highly to the energetic stability of the folded structure of their sequence, but only slightly, if at all, to the stability of the folded reverse complement. Sequences in the RNA World might thereby combine stable folding of the ribozyme with an unstructured, reverse-complementary genome, resulting in a "division of labor" between the strands. We demonstrate this strategy using computational simulations of RNA folding and an experimental model of early replication, nonenzymatic template-directed RNA primer extension. Additional study is needed to solve other problems associated with a complete replication cycle, including separation of strands after copying. Interestingly, viroid RNA sequences, which have been suggested to be relics of an RNA World (Diener, Proc Natl Acad Sci USA 86:9370-9374, 1989), also show significant asymmetry in folding energy between the infectious (+) and template (-) strands due to G:U pairing, suggesting that this strategy may even be used by replicators in the present day.
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- Findingown data
Control templates V and V-RC, which have no G:U pairs and equal folding free energy, show similar primer extension rates.
“As a control, we compared template V (ΔG = −26 kcal/mol; no G:U pairs) with its reverse complement V-RC (ΔG = −26 kcal/mol; no G:U pairs); primer extension from P and P-V-RC, respectively, occurred at similar rates (Table 1).”
Quote in the paperSubstantial claim - Findingown data
The stabilization ratio (RG:U) correlates with the asymmetry between viroid strands.
“the stabilization ratio correlated well with asymmetry between the strands (Figure 3D)”
Quote in the paperSubstantial claim - Findingown data
Folding is anti-correlated with extension rate in nonenzymatic template-directed RNA primer extension.
“Folding is anti-correlated with extension rate of nonenzymatic template-directed synthesis.”
- Also stated in: § Folding is anti-correlated with extension rate of nonenzymatic template-directed synthesis. · plain
“In general, as expected, templates able to self-fold well had very low extension rates compared to relatively unfolded templates.”
Quote in the paperSubstantial claim - Also stated in: § Folding is anti-correlated with extension rate of nonenzymatic template-directed synthesis. · plain
- Findingown data
The predicted proportion of primer in pre-reaction complexes correlates with experimentally measured extension rates for templates I-XIII (Spearman rho = 0.85, p = 2.2 x 10^-4).
“we found that the predicted proportion of primer in pre-reaction complexes for I-XIII correlated with extension rates (Figure 2C; Spearman’s rank correlation ρ=0.85, p=2.2 ×10−4)”
Quote in the paperSubstantial claim - Findingcitation
Viroid RNA sequences show significant asymmetry in folding energy between infectious (+) and template (-) strands due to G:U pairing.
“viroid RNA sequences, which have been suggested to be relics of an RNA World (Diener 1989), also show significant asymmetry in folding energy between the infectious (+) and template (−) strands due to G:U pairing”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Diener 1989 source
Not checked in the free run.
- Findingown data
When ΔΔGstrand is calculated without allowing G:U pairs, only a slight difference is seen between viroids and controls, suggesting most of the effect is attributable to G:U pairs.
“If ΔΔGstrand is calculated without allowing G:U pairs, only a slight difference is seen between the distribution of viroids and that of controls, suggesting that while there may be a small degree of stabilization from other factors, most of the effect is attributable to G:U pairs”
Quote in the paperSubstantial claim - Findingown data
G:U wobble pairing contributes greater stability to the (+) strand than to the (-) strand of viroids.
“G:U wobble pairing indeed contributed greater stability to the (+) strand (Figure 3C).”
Quote in the paperSubstantial claim - Findingown data
Even stably folded templates support template-directed synthesis at rates significantly higher than the no-template control (0.04 +/- 0.02 hr^-1).
“even these slow rates were significantly higher than the reaction in absence of template (0.04 ± 0.02 hr−1), suggesting that substantial template-directed synthesis can occur even on quite stably folded sequences.”
Quote in the paperSubstantial claim - Findingown data
The extension rates of Asym and Asym-RC differ by a factor of 100.
“The extension rates of Asym and Asym-RC, using primer P-Asym and P-Asym-RC, respectively, differed by a factor of 100 (Table 1; Figure 2D)”
Quote in the paperSubstantial claim - Findingown data
The infectious (+) strand of viroids has lower free energy than the templating (-) strand due in large part to G:U pairs.
“Our analysis of viroid RNA sequences suggests that this is the case, with the infectious (+) strand having lower free energy than the templating (−) strand due in large part to G:U pairs.”
Quote in the paperSubstantial claim - Findingown data
The extension rate of Asym was close to the non-templated rate of extension, suggesting the observed difference is near the maximum detectable in this assay.
“The extension rate of Asym was close to the non-templated rate of extension, suggesting that the observed difference is near the maximum that would be detectable in this assay.”
Quote in the paperSubstantial claim - Findingown data
Experimental estimates of the proportion of primer in the hybridized state generally agree with thermodynamic predictions.
“These were in general agreement; exceptions may be due to kinetic trapping or the presence of higher-order complexes that are not considered in the RNA folding algorithm.”
Quote in the paperNot a substantial claim - Interpretationown data
Structural accessibility is a prerequisite for the extension reaction.
“consistent with structural accessibility being a prerequisite for reaction.”
Quote in the paperSubstantial claim - Interpretationown data
G:U wobble pairing causes the asymmetry in folding between viroid strands.
“suggesting that G:U wobble pairing causes the asymmetry in folding between strands.”
Quote in the paperSubstantial claim - Premisecitation
Secondary structure disrupts primer binding and unfolding during extension.
“the fact that secondary structure disrupts primer binding and unfolding during extension is widely recognized (Peters et al. 2004; Nolan et al. 2006).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Non-Watson-Crick pairings are relatively common in RNA structures.
“Such non-Watson-Crick pairings are relatively common in RNA structures (Leontis et al. 2002)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Leontis et al. 2002 source
Not checked in the free run.
- Interpretationreasoning
This strategy may be used by replicators in the present day.
“suggesting that this strategy may even be used by replicators in the present day.”
Quote in the paperNot a substantial claim - Interpretationown data
Wobble pairing could enable a division of labor between a ribozyme strand and a genome strand in RNA World life.
“Here we suggest that the ability of RNA to form wobble pairs, particularly G:U, would enable a ‘division of labor’ between the ribozyme strand and the genome strand.”
Quote in the paperSubstantial claim - Interpretationown data
The paradox of ribozyme templates can be alleviated by wobble pairing.
“our results suggest that the paradox of ribozyme templates can be alleviated by wobble pairing, a prominent feature of RNA.”
Quote in the paperSubstantial claim - Interpretationown data
A good template sequence (genome) could encode a well-folded sequence (ribozyme) despite the palindromic nature of Watson-Crick base pairing.
“This difference implies that a good template sequence (genome) could encode a well-folded sequence (ribozyme) despite the palindromic nature of Watson-Crick base pairing.”
Quote in the paperSubstantial claim - Interpretationown data
G:U wobble pairs cause a large asymmetry in templating ability between a sequence and its reverse complement.
“illustrating that the use of G:U pairs did result in a large asymmetry between the templating ability of the two strands.”
Quote in the paperSubstantial claim - Interpretationown data
The poor templating ability of a highly structured RNA sequence can be countered in its reverse complement through increased G:U wobble pairing.
“Our study indicates that the poor templating ability of a highly structured RNA sequence can be countered in its reverse complement through increased G:U wobble pairing.”
Quote in the paperSubstantial claim - Study design and conductown data
Computational RNA secondary structure folding is not sufficient to quantitatively predict extension rates.
“While computational RNA secondary structure folding is not sufficient to quantitatively predict extension rates”
Quote in the paperSubstantial claim - Interpretationcitation
The observed asymmetry in viroids is likely the outcome of ongoing selection.
“Since viroids undergo mutation at a very high rate (Gago et al. 2009), the observed asymmetry is likely to be the outcome of ongoing selection.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Gago et al. 2009 source
Not checked in the free run.
- Interpretationreasoning
Therefore the complement of a well-folded ribozyme would also be expected to fold well.
“Therefore the complement of a well-folded ribozyme would also be expected to fold well.”
Quote in the paperSubstantial claim
- May combine two claims. 11
- The quote only partly states this claim. 1
- Classified as probably not a substantial claim. 12
May combine two claims.
Findingown dataThe distribution of ΔΔGstrand for 40 viroids is shifted to the left and differs significantly from that of base-composition-matched randomized controls (2-sample Kolmogorov-Smirnov test p = 0.0084).
“the ΔΔGstrand of viroids was shifted to the left and the distribution differed significantly from that of the controls (2-sample Kolmogorov-Smirnov test: p = 0.0084).”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataTemplates classified as obstructed (less than 50% primer in pre-reaction complex) have lower experimentally observed extension rates than accessible templates (at least 50% primer in pre-reaction complex).
“A clear difference in experimentally observed extension rates was observed between these classes (Figure 2C, Supplementary Figure 1)”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAllowing G:U pairing in folding simulations increases the proportion of random sequences that are asymmetric, with about 1.5% asymmetric by the percentile definition versus 0.08% when G:U is disallowed.
“then about 1.5% of random sequences are asymmetric by this definition. However, if we disallow G:U wobble pairs in the folding algorithm, the proportion of asymmetric sequences is 20-fold smaller (0.08%, by the percentile definition).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Findingnone givenThe extension rates of accessible sequences are quite variable, presumably due to factors other than secondary structure.
“although extension rates of ‘accessible’ sequences are quite variable, presumably due to factors other than secondary structure (e.g., kinetic effects).”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationG:U wobble pairing contributes strongly to the energetic stability of a folded RNA sequence but only weakly, if at all, to the stability of its reverse complement.
“Unlike Watson-Crick base pairs, wobble pairs contribute highly to the energetic stability of the folded structure of their sequence, but only slightly, if at all, to the stability of the folded reverse complement.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Turner and Mathews 2010 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
InterpretationreasoningWobble pairs other than G:U may display similar, albeit attenuated, advantages.
“wobble pairs other than G:U may display similar, albeit attenuated, advantages.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationWobble pairing results in mispairings that substantially lower fidelity, limiting the amount of information that can be propagated.
“wobble pairing also results in mispairings that substantially lower fidelity, limiting the amount of information that can be propagated in such a system (Eigen 1971; Leu et al. 2011).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S4 (based).
Premisenone givenThis information had not been previously applied to the paradox of RNA World templates or to understand modern-day RNA replicators.
“However, to our knowledge, this information had not been previously applied to the paradox of RNA World templates or to understand modern-day RNA replicators.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe effect of base composition on folding energy can be deduced from nearest-neighbor models of RNA folding.
“The effect of base composition on folding energy can be deduced from nearest-neighbor models of RNA folding (Kennedy et al. 2010; Lorenz et al. 2011; Derr et al. 2012)”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationG/T-rich DNA sequences improve the efficiency of an RNA polymerase ribozyme, presumably by increasing non-specific associations.
“G/T-rich DNA sequences improve the efficiency of an RNA polymerase ribozyme, presumably by increasing non-specific associations (Yao and Muller 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Yao and Muller 2011 source
Not checked in the free run.
May combine two claims.
PremisereasoningWell-folded RNA sequences are poor templates for copying, while poorly folded sequences are unlikely to be good ribozymes.
“well-folded sequences are poor templates for copying, but poorly folded sequences are unlikely to be good ribozymes.”
- Also stated in: § Introduction · hedged
“good template sequences lack structure, while ribozymes tend to adopt well-folded structures, so these two desirable properties seem to be mutually exclusive.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Szabo et al. 2002 source
Not checked in the free run.
- cites Muller 2006 source
Not checked in the free run.
- The authors state this as an assumption: Well-folded structures are a prerequisite for catalytic activity.
- Rests on an assumption: An RNA sequence must exist in an extended conformation accessible to primer and substrate nucleotides to act as a template for copying.
- Also stated in: § Introduction · hedged
May combine two claims.
PremisecitationAssociation of the activated nucleotide poises the complex for reaction, and bond formation is essentially irreversible.
“Association of the activated nucleotide poises the complex for reaction, and bond formation is essentially irreversible (Figure 1E).”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationRNA-based biochemistry represents an attractive platform for minimal synthetic self-replicating life since there is no need to support DNA and protein synthesis.
“RNA-based biochemistry also represents an attractive platform for minimal synthetic self-replicating life since there is no need to support DNA and protein synthesis (Szostak et al. 2001; Muller 2006; Joyce 2009; Cheng and Unrau 2010).”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone givenThis effect is weak relative to selection pressures favoring asymmetry.
“but apparently this effect is weak relative to selection pressures favoring asymmetry.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationOne possible strategy to overcome the paradox is division of labor between the two strands of RNA, with one strand folding into a ribozyme and the other functioning as genome.
“One possible strategy to overcome this paradox is ‘division of labor’ between the two strands of the RNA, with one strand folding into a ribozyme and the other functioning as genome (Chen et al. 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Chen et al. 2006
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationLower complexity sequences are more prone to multiple misfolded states and might have been disfavored by prebiotic synthetic processes.
“lower complexity sequences are more prone to multiple misfolded states and might have been disfavored by prebiotic synthetic processes (Derr et al. 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Derr et al. 2012 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationViroids in family Avsunviroidae contain hammerhead self-cleavage motifs in both (+) and (-) strand to process oligomeric intermediates into monomeric forms.
“viroids in family Avsunviroidae contain hammerhead self-cleavage motifs in both the (+) and (−) strand to process oligomeric intermediates into monomeric forms (Daros et al. 2006)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Daros et al. 2006 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe RNA World theory's plausibility is bolstered by experimental findings including centrality of RNA nucleotides in metabolism, nature of the ribosome, and abiotic synthesis of RNA nucleosides.
“The plausibility of this theory is bolstered by several experimental findings, including the centrality of RNA nucleotides in metabolism, the nature of the ribosome (a ribozyme) (Ban et al. 2000; Wimberly et al. 2000; Yusupov et al. 2001), and the abiotic synthesis of RNA nucleosides (Powner et al. 2009).”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationSeveral challenges must be overcome to create an experimental model of RNA World replication, including error catastrophe and difficulty separating strands of moderate length.
“Several challenges must be overcome to create an experimental model of RNA World replication, including the so-called ‘error catastrophe’ and the difficulty of separating strands of moderate length (Szostak 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Szostak 2013 source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisereasoningThe folding capacity of a given RNA sequence and its complement are likely to be similar at the secondary structure level, since a given structural element is palindromic in the stem portion.
“However, at first glance, the folding capacity of a given RNA sequence and its complement are likely to be similar at the secondary structure level, since a given structural element is palindromic in the stem portion (Figure 1A).”
Quote in the paperSubstantial claimMay combine two claims.
PremisereasoningThe (-) strand of viroids is expected to be relatively optimized for templating while the (+) strand is optimized for folding-dependent functions related to infectivity.
“Therefore, we expect the (−) strand to be relatively optimized for templating while the (+) strand is optimized for folding-dependent functions related to infectivity.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningSegregating the genomic function into a specialized chemical form with reduced wobble pairing (DNA) would relieve the conflicting pressures of ribozyme folding and templating ability while improving fidelity.
“Further ‘division of labor’ segregating the genomic function into a specialized chemical form with reduced wobble pairing (DNA) would ultimately relieve the conflicting pressures of ribozyme folding and templating ability while improving the fidelity of information transfer.”
Quote in the paperSubstantial claim
The paper relies on this without support.
The dual role of RNA in early life requires both good templating ability and stable folding.
“The hypothesized dual role of RNA as both information carrier and biocatalyst during the earliest stages of life requires a combination of features: good templating ability (for replication) and stable folding (for ribozymes).”
The authors state this as an assumption.
Well-folded structures are a prerequisite for catalytic activity.
“Well-folded structures are assumed to be a prerequisite for catalytic activity.”
The paper relies on this without support.
An RNA sequence must exist in an extended conformation accessible to primer and substrate nucleotides to act as a template for copying.
“an RNA sequence must presumably exist in an extended conformation that is accessible to a primer and substrate nucleotides in order to act as a template for copying.”
The authors state this as an assumption.
The primer-template complex exists in equilibrium with self-associated template and free primer according to the free energy difference.
“If the template itself can fold, the primer-template complex presumably exists in equilibrium with self-associated template and free primer according to the free energy difference (ΔG1).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
RNA can form wobble pairs, causing a ribozyme and its reverse complement to have quite different folding energies, a pattern observed in RNA viroids.
“This feature can cause a ribozyme and its reverse complement to have quite different folding energies, a pattern which can be observed in RNA viroids [137].”
From The RNA world as a model system to study the origin of life (2015) · cites this paper as [137]
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Kennedy, R., Lladser, M. E., Wu, Z., Zhang, C., Yarus, M., De Sterck, H., & Knight, R. (2010) · RNA · doi:10.1261/rna.1923210 · Cited by 19 · see citing works
Polymerase ribozyme efficiency increased by G/T-rich DNA oligonucleotides
Yao, C., & Müller, U. F. (2011) · RNA · doi:10.1261/rna.2726811 · Cited by 8 · see citing works
Flagged first, then by citations
1 of the 41 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Gesteland R, Cech T, Atkins J (eds) (2006) The RNA world. Cold Spring Harbor Laboratory Press, New York
Cited by
Sorted by citations
The RNA world as a model system to study the origin of life
Pressman, A., Blanco, C., & Chen, I. A. (2015) · Current Biology · doi:10.1016/j.cub.2015.06.016 · Cited by 225 · see citing works
Self-citationViroids: Survivors from the RNA World?
Flores, R., Gago‐Zachert, S., Serra, P., Sanjuán, R., & Elena, S. F. (2014) · Annual Review of Microbiology · doi:10.1146/annurev-micro-091313-103416 · Cited by 164 · see citing works
The Conservation and Function of RNA Secondary Structure in Plants
Vandivier, L. E., Anderson, S. J., Foley, S. W., & Gregory, B. D. (2016) · Annual Review of Plant Biology · doi:10.1146/annurev-arplant-043015-111754 · Cited by 101 · see citing works
Top-Down Causation and the Rise of Information in the Emergence of Life
Walker, S. I. (2014) · Information · doi:10.3390/info5030424 · Cited by 57 · see citing works
The origin of a primordial genome through spontaneous symmetry breaking
Takeuchi, N., Hogeweg, P., & Kaneko, K. (2017) · Nature Communications · doi:10.1038/s41467-017-00243-x · Cited by 48 · see citing works
Physical non-equilibria for prebiotic nucleic acid chemistry
Ianeselli, A., Salditt, A., Mast, C. B., Ercolano, B., Kufner, C. L., Scheu, B., & Braun, D. (2023) · Nature Reviews Physics · doi:10.1038/s42254-022-00550-3 · Cited by 50 · see citing works
Viroids: “living fossils” of primordial RNAs?
Diener, T. O. (2016) · Biology Direct · doi:10.1186/s13062-016-0116-7 · Cited by 52 · see citing works
In the Beginning was a Mutualism - On the Origin of Translation
Vitas, M., & Dobovišek, A. (2018) · Origins of Life and Evolution of Biospheres · doi:10.1007/s11084-018-9557-6 · Cited by 34 · see citing works
Czárán, T., Könnyű, B., & Szathmáry, E. (2015) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2015.06.002 · Cited by 37 · see citing works
He, C., Lozoya‐Colinas, A., Gállego, I., Grover, M. A., & Hud, N. V. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz496 · Cited by 27 · see citing works
Template-Free Assembly of Functional RNAs by Loop-Closing Ligation
Wu, L.-F., Liu, Z., Roberts, S. J., Su, M., Szostak, J. W., & Sutherland, J. D. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.2c05601 · Cited by 21 · see citing works
Attwater, J., Augustin, T. L., Curran, J. F., Kwok, S., Ohlendorf, L., Gianni, E., & Holliger, P. (2025) · Nature Chemistry · doi:10.1038/s41557-025-01830-y · Cited by 27 · see citing works
The Power Without the Glory: Multiple Roles of Hydrogen Peroxide in Mediating the Origin of Life
Ball, R. V., & Brindley, J. (2019) · Astrobiology · doi:10.1089/ast.2018.1886 · Cited by 22 · see citing works
The life story of hydrogen peroxide II: a periodic pH and thermochemical drive for the RNA world
Ball, R. V., & Brindley, J. (2015) · Journal of The Royal Society Interface · doi:10.1098/rsif.2015.0366 · Cited by 20 · see citing works
The origin of the central dogma through conflicting multilevel selection
Takeuchi, N., & Kaneko, K. (2019) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2019.1359 · Cited by 18 · see citing works
Cas6 processes tight and relaxed repeat RNA via multiple mechanisms: A hypothesis
Sefcikova, J., Roth, M. O., Yu, G., & Li, H. (2017) · BioEssays · doi:10.1002/bies.201700019 · Cited by 17 · see citing works
Emergence of ribozyme and tRNA-like structures from mineral-rich muddy pools on prebiotic earth
Roy, S., Bapat, N. V., Derr, J., Rajamani, S., & Sengupta, S. (2020) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2020.110446 · Cited by 11 · see citing works
Self-citationOn a quest of reverse translation
Vitas, M., & Dobovišek, A. (2016) · Foundations of Chemistry · doi:10.1007/s10698-016-9260-5 · Cited by 13 · see citing works
RNA Back and Forth: Looking through Ribozyme and Viroid Motifs
Maurel, M., Leclerc, F., Vergne, J., & Zaccaı̈, G. (2019) · Viruses · doi:10.3390/v11030283 · Cited by 11 · see citing works
Thiosulfate-Hydrogen Peroxide Redox Oscillator as pH Driver for Ribozyme Activity in the RNA World
Ball, R. V., & Brindley, J. (2015) · Origins of Life and Evolution of Biospheres · doi:10.1007/s11084-015-9448-z · Cited by 10 · see citing works
In silico discovery and modeling of non-coding RNA structure in viruses
Moss, W. N., & STEITZ, J. A. (2015) · Methods · doi:10.1016/j.ymeth.2015.06.015 · Cited by 10 · see citing works
Norris, V., & Jacques Demongeot, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232112915 · Cited by 7 · see citing works
Takeuchi, N., Mitarai, N., & Kaneko, K. (2021) · Genetics · doi:10.1093/genetics/iyab182 · Cited by 7 · see citing works
Reversible Switching of Cooperating Replicators
Urtel, G., Rind, T., & Braun, D. (2017) · Physical Review Letters · doi:10.1103/physrevlett.118.078102 · Cited by 8 · see citing works
von der Dunk, S. H. A., Colizzi, E. S., & Hogeweg, P. (2017) · Life · doi:10.3390/life7040043 · Cited by 7 · see citing works
Könnyű, B., & Czárán, T. (2014) · BMC Evolutionary Biology · doi:10.1186/s12862-014-0234-8 · Cited by 7 · see citing works
On the emergence of structural complexity in RNA replicators
Oliver, C., Reinharz, V., & Waldispühl, J. (2019) · RNA · doi:10.1261/rna.070391.119 · Cited by 5 · see citing works
Physical aspects of origins of life scenarios
Blokhuis, A. W. P. (2019) · doi:10.70675/6cda43e2za86ez4758z9553zae340bcda014 · Cited by 3 · see citing works
RNA Back and Forth: Looking Through Ribozyme and Viroid MotifsPreprint
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Which came first: the chicken, the egg, or guanine?
Kankia, B. I. (2023) · RNA · doi:10.1261/rna.079613.123 · Cited by 5 · see citing works
The tri-flow adaptiveness of codes in major evolutionary transitions
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Generalizing the central dogma as a cross-hierarchical principle of biology
Takeuchi, N., & Kaneko, K. (2025) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2024.0296 · Cited by 1 · see citing works
Evolution of the division of labour between templates and catalysts in spatial replicator models
Fu, Y., & Takeuchi, N. (2024) · Journal of Evolutionary Biology · doi:10.1093/jeb/voae098 · Cited by 1 · see citing works
Can artificial neural replicators be useful for studying RNA replicators?
Ezhov, A. A. (2020) · Archives of Virology · doi:10.1007/s00705-020-04779-0 · Cited by 1 · see citing works
Emergence of ribozyme and tRNA-like structures from mineral-rich muddy pools on prebiotic earthPreprint
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Self-citationThe origin of the central dogma through conflicting multilevel selectionPreprint
Takeuchi, N., & Kaneko, K. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/515767 · Cited by 1 · see citing works
Thiosulfate-hydrogen peroxide redox oscillator as pH driver for ribozyme activity in the RNA worldPreprint
Ball, R. V., & Brindley, J. (2015) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/020693 · Cited by 1 · see citing works
Könnyű, B., & Czárán, T. (2015) · Origins of Life and Evolution of Biospheres · doi:10.1007/s11084-015-9409-6 · Cited by 1 · see citing works
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- Authors
- Ivica, N. A., Obermayer, B., Campbell, G. W., Rajamani, S., Gerland, U., & Chen, I. A.
- Affiliations
- Harvard University (US)
- University of California, Santa Barbara (US)
- Ludwig-Maximilians-Universität München (DE)
- Corresponding author
- Chen, Irene A.
- ORCID
- Venue
- Journal of Molecular Evolution
- Published
- 2013-09
- Volume
- 77
- Issue
- 3
- Pages
- 55-63
- ISSN
- 0022-2844 (ISSN-L)
- 1432-1432
- PMC
- PMC12051476
- OpenAlex
- W1982686137
- Cited by
- 42
- References
- 41
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 6 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 6 · 2014: 3
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Molecular Evolution (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Francis Crick Institute
- National Institute of General Medical Sciences (P50GM068763, GM-068763)
- 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
- RNA world, ribozymes, RNA replication, reverse complement, strand asymmetry, viroid RNA, origin of life
- MeSH terms
- Models, Molecular, RNA, RNA, Catalytic, Sequence Analysis, RNA, Base Pairing, RNA Folding
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-04.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-04.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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