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Record W4409186915 · doi:10.1016/j.jmb.2025.169124

An RNA Condensate Model for the Origin of Life

2025· review· en· W4409186915 on OpenAlexafffund
Jacob L. Fine, Alan M. Moses

Bibliographic record

VenueJournal of Molecular Biology · 2025
Typereview
Languageen
FieldPhysics and Astronomy
TopicOrigins and Evolution of Life
Canadian institutionsUniversity of Toronto
FundersCanadian Institutes of Health Research
KeywordsAbiogenesisRNARNA world hypothesisChemistryBiologyGeneticsRibozymeGene

Abstract

fetched live from OpenAlex

Proposed mechanism of compartmentalization and self-replication via an RNA condensate: (1) condensation, (2) RNA-templated polymerization (green arrows) and growth, and (3) division. • RNA condensates may have served as self-replicating catalysts for the origin of life and the RNA World. • RNA condensates formed by short RNAs lower the error threshold and unify replication and compartmentalization. • RNA condensates may spontaneously begin a ‘condensate chain reaction’ leading to natural selection. • Within a standard polymer physics framework, key parameters for the model are defined. • These hypotheses about the origin of life can readily be tested by experiment or simulation. The RNA World hypothesis predicts that self-replicating RNAs evolved before DNA genomes and coded proteins. Despite widespread support for the RNA World, self-replicating RNAs have yet to be identified in a natural context, leaving a key ‘missing link’ for this explanation of the origin of life. Inspired by recent work showing that condensates of charged polymers are capable of catalyzing chemical reactions, we consider a catalytic RNA condensate as a candidate for the self-replicating RNA. Specifically, we propose that short, low-complexity RNA polymers formed catalytic condensates capable of templated RNA polymerization. Because the condensate properties depend on the RNA sequences, RNAs that formed condensates with improved polymerization and demixing capacity would be amplified, leading to a ‘condensate chain reaction’ and evolution by natural selection. Many of the needed properties of this self-replicating RNA condensate have been realized experimentally in recent studies and our predictions could be tested with current experimental and theoretical tools. Our theory addresses central problems in the origins of life: (i) the origin of compartmentalization, (ii) the error threshold for the accuracy of templated replication, (iii) the free energy cost of maintaining an information-rich population of replicating RNA polymers. Furthermore, we note that the extant nucleolus appears to satisfy many of the requirements of an evolutionary relic for the model we propose. More generally, we suggest that future work on the origin of life would benefit from condensate-centric biophysical models of RNA evolution.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.986
Threshold uncertainty score0.458

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.043
GPT teacher head0.379
Teacher spread0.336 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations10
Published2025
Admission routes2
Has abstractyes

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