Highly Efficient Self-Replicating RNA Enzymes
Open accessAbstract
An RNA enzyme has been developed that catalyzes the joining of oligonucleotide substrates to form additional copies of itself, undergoing self-replication with exponential growth. The enzyme also can cross-replicate with a partner enzyme, resulting in their mutual exponential growth and enabling self-sustained Darwinian evolution. The opportunity for inventive evolution within this synthetic genetic system depends on the diversity of the evolving population, which is limited by the catalytic efficiency of the enzyme. Directed evolution was used to improve the efficiency of the enzyme and increase its exponential growth rate to 0.14 min(-1), corresponding to a doubling time of 5 min. This is close to the limit of 0.21 min(-1) imposed by the rate of product release, but sufficient to enable more than 80 logs of growth per day.
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The replication process can be sustained indefinitely by replenishing the supply of substrates, in one case achieving an overall amplification factor of 10^100-fold in 37.5 h.
“The replication process can be sustained indefinitely by replenishing the supply of substrates, in one case achieving an overall amplification factor of 10 100 -fold in 37.5 h (Robertson and Joyce 2014).”
From Protocells and RNA Self-Replication (2018) · cites this paper as Robertson and Joyce 2014
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Cites
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“, 2011), and when made to operate at near-freezing temperatures for 7 days can generate products up to 206 nucleotides in length (Attwater et al., 2013).”
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Cited by
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Protocells and RNA Self-Replication
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Chemical Fueling Enables Molecular Complexification of Self‐Replicators**
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Experimental fitness landscapes to understand the molecular evolution of RNA-based life
Athavale, S. S., Spicer, B., & Chen, I. A. (2014) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2014.09.008 · Cited by 25 · see citing works
- Authors
- Robertson, M. P., & Joyce, G. F.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Joyce, Gerald F.
- ORCID
- Joyce, Gerald F.
- Venue
- Chemistry & Biology
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 21
- Issue
- 2
- Pages
- 238-245
- ISSN
- 1074-5521 (ISSN-L)
- PMC
- PMC3943892
- OpenAlex
- W2087360525
- Cited by
- 105
- References
- 7
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 7 · 2023: 7 · 2022: 6 · 2021: 11 · 2020: 16 · 2019: 10 · 2018: 10 · 2017: 7 · 2016: 8 · 2015: 7 · 2014: 5
- FWCI
- 4.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Chemistry & Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Aeronautics and Space Administration (NNX10AQ91G, R01GM065130)
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM065130)
- 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
- ribozymes, self-replicating RNA, oligonucleotide ligation, exponential growth, Darwinian evolution, directed evolution, catalytic efficiency, RNA catalysis
- MeSH terms
- Base Sequence, Biological Evolution, Kinetics, Nucleic Acid Conformation, Substrate Specificity, Gene Library, RNA, Catalytic
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