Exploring the space of self-reproducing ribozymes using generative models

Estimating the plausibility of RNA self-reproduction is central to origin-of-life scenarios. However, this property has been shown in only a handful of catalytic RNAs. Here, we compare models for their generative power in diversifying a reference ribozyme, based on statistical covariation and secondary structure prediction, and experimentally test model predictions using high-throughput sequencing. Leveraging statistical physics methods, we compute the number of ribozymes capable of autocatalytic self-reproduction from oligonucleotide fragments to be over 10<sup>39</sup>, with sequences found up to 65 mutations from the original sequence and 99 mutations away from each other, far beyond the 10 mutations achieved by deep mutational scanning. The findings demonstrate an efficient method for exploring RNA sequence space, and provide quantitative data on self-reproducing RNA that further illuminates the potential pathways to abiogenesis.

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Publication Details

Journal
Nature Communications
Published
2025-08-22
DOI
https://doi.org/10.1038/s41467-025-63151-5
Citations
5
Primary Topic
RNA and protein synthesis mechanisms
Type
article
Field-Weighted Citation Impact
4.03

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article

Exploring the space of self-reproducing ribozymes using generative models

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5 citations
Nature Communications
RNA and protein synthesis mechanisms
4.03
article

Exploring the space of self-reproducing ribozymes using generative models

Eric J. Hayden, Francesco Zamponi, Martin Weigt, Vaitea Opuu, Philippe Nghe, Matteo Smerlak, Camille N. Lambert, Francesco Calvanese, Polina Pavlinova
article en
5 citations

Abstract

Estimating the plausibility of RNA self-reproduction is central to origin-of-life scenarios. However, this property has been shown in only a handful of catalytic RNAs. Here, we compare models for their generative power in diversifying a reference ribozyme, based on statistical covariation and secondary structure prediction, and experimentally test model predictions using high-throughput sequencing. Leveraging statistical physics methods, we compute the number of ribozymes capable of autocatalytic self-reproduction from oligonucleotide fragments to be over 10<sup>39</sup>, with sequences found up to 65 mutations from the original sequence and 99 mutations away from each other, far beyond the 10 mutations achieved by deep mutational scanning. The findings demonstrate an efficient method for exploring RNA sequence space, and provide quantitative data on self-reproducing RNA that further illuminates the potential pathways to abiogenesis.

Nature CommunicationsVol. 16(1)
Boise State University (US), Centre National de la Recherche Scientifique (FR), Sorbonne Université (FR), Max Planck Institute for Mathematics in the Sciences (DE), Biologie Computationnelle, Quantitative et Synthétique (FR), Max Planck Institute for Mathematics (DE), Capital Fund Management (France) (FR), Sapienza University of Rome (IT), ESPCI Paris (FR)
Agence Nationale de la Recherche, Institut Pierre-Gilles de Gennes, Horizon 2020 Framework Programme
Openalex Percentile: Top 6%
RNA and protein synthesis mechanisms
4.03
DOIOpen Access PDFOpenAlex
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