Minimal RNA self-reproduction discovered from a random pool of oligomers

Mizuuchi, Ryo; Ichihashi, Norikazu

doi:10.1039/d3sc01940c

Cited by 3 publications

(2 citation statements)

References 54 publications

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“…The existence of a larger neutral space is already supported by the fact that we could diversify a GII other than Azo (Fig. S14, Supplementary Material 'Phormidium'), and the existence of structurally distinct autocatalytic RNAs (31). The density of self-reproducers may thus be many decades higher, making evidence for a probable RNA origin of life within reach.…”

Section: Main Textmentioning

confidence: 62%

Expanding the space of self-reproducing ribozymes using probabilistic generative models

Lambert,

Opuu,

Calvanese

et al. 2024

Preprint

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Estimating the plausibility of RNA self-reproduction is central to origin-of-life scenarios but self-reproduction has been shown in only a handful of systems. Here, we populated a vast sequence space of ribozymes using statistical covariation models and secondary structure prediction. Experimentally assayed sequences were found active as far as 65 mutations from a reference natural sequence. The number of potentially generated sequences together with the experimental success rate indicate that at least ∼1039such ribozymes may exist. Randomly sampled artificial ribozymes exhibited autocatalytic self-reproduction akin to the reference sequence. The combination of high-throughput screening and probabilistic modeling considerably improves our estimation of the number of self-reproducing systems, paving the way for a statistical approach to the origin of life.

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Section: Main Textmentioning

confidence: 62%

Expanding the space of self-reproducing ribozymes using probabilistic generative models

Lambert,

Opuu,

Calvanese

et al. 2024

Preprint

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“…As Darwinian evolution requires the self-reproduction of chemical systems, the informational capacity should have been large enough to encode the full functionality. [1][2][3] Although explorations in catalytically active RNA, ribozymes, have identified RNA oligomers as short as 20-30 nucleotides (nt) with specific functions, including ligation, cleavage, binding, and replication, [4][5][6] the emergence of continuous reproductive systems requires a genetic molecule encoding more functionalities, such as decoding and compartmentalization. [2,3,5,7] Thus, the required informational capacity is expected to increase to more than kilo-to megabases.…”

Section: Introductionmentioning

confidence: 99%

Slow Freeze‐Thaw Cycles Enhanced Hybridization of Kilobase DNA with Long Complementary Sticky Ends

Noda,

Nomura,

Takahashi

et al. 2024

ChemSystemsChem

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The creation of large information molecules may have played an essential role in the origins of life. In this study, we conducted slow freeze‐thaw (F/T) experiments to test the possibility of enhanced hybridization between the complementary sticky ends attached to kilobase‐sized DNA fragments at sub‐nanomolar concentrations. DNA fragments of 2‐ and 3‐kilobase pairs (kbp) with 50‐base complementary sticky ends that can form 5 kbp‐sized hybridization products were mixed. While simple incubation provided little hybridization product, significantly effective hybridization was observed after freezing and thawing at a controlled time rate (<0.3 K min⁻¹), even with small DNA concentrations (<1 nM). Furthermore, slow thawing had a more effect on hybridization than slow freezing. The reaction efficiency was reduced by rapid thawing instead of slow thawing, suggesting that the eutectic phase concentration played an important role in hybridization. A slow F/T cycle was effective even for the hybridization reaction between two 10 kbp DNA fragments, which yielded a 20 kbp product at sub‐nanomolar concentrations. Repeating the slow F/T cycle significantly improved the reaction efficiency. The possible role of the F/T cycles in early Earth environments is discussed here.

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How biophysics shapes the origins of life: a 21st IUPAB/62nd BSJ joint congress symposium overview

Jia,

Mizuuchi

2024

Biophys Rev

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Minimal RNA self-reproduction discovered from a random pool of oligomers

Abstract: The emergence of RNA self-reproduction from prebiotic components would have been crucial in developing a genetic system during the origins of life. However, all known self-reproducing RNA molecules are complex...

Cited by 3 publications

References 54 publications

Expanding the space of self-reproducing ribozymes using probabilistic generative models

Expanding the space of self-reproducing ribozymes using probabilistic generative models

Slow Freeze‐Thaw Cycles Enhanced Hybridization of Kilobase DNA with Long Complementary Sticky Ends

How biophysics shapes the origins of life: a 21st IUPAB/62nd BSJ joint congress symposium overview

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