Evolution in an RNA World
Open accessAbstract
A long-standing research goal has been to develop a self-sustained chemical system that is capable of undergoing Darwinian evolution. The notion of primitive RNA-based life suggests that this goal might be achieved by constructing an RNA enzyme that catalyzes the replication of RNA molecules, including the RNA enzyme itself. This reaction was demonstrated recently in a cross-catalytic system involving two RNA enzymes that catalyze each other's synthesis from a total of four component substrates. The cross-replicating RNA enzymes undergo self-sustained exponential amplification at a constant temperature in the absence of proteins or other biological materials. Amplification occurs with a doubling time of approximately 1 hour and can be continued indefinitely. Small populations of cross-replicating RNA enzymes can be made to compete for limited resources within a common environment. The molecules reproduce with high fidelity but occasionally give rise to recombinants that also can replicate. Over the course of many "generations" of selective amplification, novel variants arise and grow to dominate the population based on their relative fitness under the chosen reaction conditions. This is the first example, outside of biology, of evolutionary adaptation in a molecular genetic system.
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RNA-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).”
From The paradox of dual roles in the RNA world: resolving the conflict between stable folding and templating ability (2013) · cites this paper as Joyce 2009
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Cites
Loop-mediated isothermal amplification of DNA
Notomi, T. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.12.e63 · Cited by 8,805 · see citing works
The origin of the genetic code
Crick, F. H. C. (1968) · Journal of Molecular Biology · doi:10.1016/0022-2836(68)90392-6 · Cited by 2,320 · see citing works
High-Resolution Molecular Discrimination by RNA
JENISON, R. D., Gill, S. C., Pardi, A., & Polisky, B. A. (1994) · Science · doi:10.1126/science.7510417 · Cited by 1,192 · see citing works
Control of gene expression by a natural metabolite-responsive ribozyme
Winkler, W. C., Nahvi, A., Roth, A., Collins, J. A., & Breaker, R. R. (2004) · Nature · doi:10.1038/nature02362 · Cited by 953 · see citing works
Isolation of New Ribozymes from a Large Pool of Random Sequences
Bartel, D. P., & Szostak, J. W. (1993) · Science · doi:10.1126/science.7690155 · Cited by 900 · see citing works
Strand displacement amplification—an isothermal, in vitro DNA amplification technique
Walker, G. T., Fraiser, M. S., Schram, J. L., Little, M. C., Nadeau, J. G., & Malinowski, D. P. (1992) · Nucleic Acids Research · doi:10.1093/nar/20.7.1691 · Cited by 857 · see citing works
Blount, Z. D., Borland, C. Z., & Lenski, R. E. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803151105 · Cited by 840 · see citing works
Self-Sustained Replication of an RNA Enzyme
Lincoln, T. A., & Joyce, G. F. (2009) · Science · doi:10.1126/science.1167856 · Cited by 670 · see citing works
Self-citationGuatelli, J. C., Whitfield, K., Kwoh, D. Y., Barringer, K., Richman, D. D., & Gingeras, T. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.5.1874 · Cited by 541 · see citing works
Directed Evolution of an RNA Enzyme
Beaudry, A. A., & Joyce, G. F. (1992) · Science · doi:10.1126/science.1496376 · Cited by 445 · see citing works
Self-citationRational design of allosteric ribozymes
Tang, J. Y., & Breaker, R. R. (1997) · Chemistry & Biology · doi:10.1016/s1074-5521(97)90197-6 · Cited by 383 · see citing works
Punctuated Evolution Caused by Selection of Rare Beneficial Mutations
Elena, S. F., Cooper, V. S., & Lenski, R. E. (1996) · Science · doi:10.1126/science.272.5269.1802 · Cited by 349 · see citing works
Tandem Riboswitch Architectures Exhibit Complex Gene Control Functions
Sudarsan, N., Hammond, M. C., Block, K. F., Welz, R., Barrick, J. E., Roth, A., & Breaker, R. R. (2006) · Science · doi:10.1126/science.1130716 · Cited by 264 · see citing works
A self-replicating ligase ribozyme
Paul, N., & Joyce, G. F. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.202471099 · Cited by 264 · cited 3× · see citing works
“Furthermore, the extensive self-complemementarity of the self-replicating enzyme is the chief reason for its limited extent of growth in the exponential phase of the reaction (Paul and Joyce 2002).”
BackgroundInfluentialSelf-citationIsolation of RNA Aptamers for Biological Cofactors by In Vitro Selection
Burgstaller, P., & Famulok, M. (1994) · Angewandte Chemie International Edition in English · doi:10.1002/anie.199410841 · Cited by 221 · see citing works
Continuous in Vitro Evolution of Catalytic Function
Wright, M. C., & Joyce, G. F. (1997) · Science · doi:10.1126/science.276.5312.614 · Cited by 207 · see citing works
Self-citationAmplification, mutation and selection of catalytic RNA
Joyce, G. F. (1989) · Gene · doi:10.1016/0378-1119(89)90033-4 · Cited by 182 · see citing works
Self-citationNonenzymatic Template-directed Synthesis of Informational Macromolecules
Joyce, G. F. (1987) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1987.052.01.008 · Cited by 121 · see citing works
Self-citationThe effect of cytidine on the structure and function of an RNA ligase ribozyme
Rogers, J., & Joyce, G. F. (2001) · RNA · doi:10.1017/s135583820100228x · Cited by 118 · see citing works
Self-citationCross-catalytic replication of an RNA ligase ribozyme.
Kim, D.-E., & Joyce, G. F. (2004) · Chemistry and Biology · doi:10.1016/j.chembiol.2004.08.021 · Cited by 112 · see citing works
Self-citationCooperative binding of effectors by an allosteric ribozyme
Jose, A. M. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.7.1631 · Cited by 91 · see citing works
Guatelli, J. C., Whitfield, K., Kwoh, D. Y., et al. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.19.7797-a · Cited by 88 · see citing works
Autocatalytic aptazymes enable ligand-dependent exponential amplification of RNA
Lam, B. J., & Joyce, G. F. (2009) · Nature Biotechnology · doi:10.1038/nbt.1528 · Cited by 62 · see citing works
Self-citationPaegel, B. M., & Joyce, G. F. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060085 · Cited by 38 · see citing works
Self-citationThe Development of Enzyme Catalytic Efficiency: An Experimental ApproachPreprint
Hermes, J. D., Blacklow, S. C., & Knowles, J. R. (1987) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1987.052.01.068 · Cited by 24 · see citing works
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Kawecki, T. J., Lenski, R. E., Ebert, D., Hollis, B., Olivieri, I., & Whitlock, M. C. (2012) · Trends in Ecology & Evolution · doi:10.1016/j.tree.2012.06.001 · Cited by 807 · see citing works
Prevolutionary dynamics and the origin of evolution
Nowak, M. A., & Ohtsuki, H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806714105 · Cited by 122 · see citing works
Ivica, N. A., Obermayer, B., Campbell, G. W., Rajamani, S., Gerland, U., & Chen, I. A. (2013) · Journal of Molecular Evolution · doi:10.1007/s00239-013-9584-x · Cited by 42 · see citing works
- Authors
- Joyce, G. F.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Joyce, G. F.
- ORCID
- Joyce, G. F.
- Venue
- Cold Spring Harbor Symposia on Quantitative Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2009-01-01
- Volume
- 74
- Issue
- 0
- Pages
- 17-23
- ISSN
- 0091-7451 (ISSN-L)
- 1943-4456
- PMC
- PMC2891321
- OpenAlex
- W2131385643
- Cited by
- 31
- References
- 25
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 3 · 2021: 1 · 2020: 1 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 4
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Symposia on Quantitative Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation
- National Aeronautics and Space Administration (R01GM065130, NNX07AJ23G)
- 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
- RNA world, self-replicating RNA, Darwinian evolution, RNA replication, molecular evolution, exponential amplification, recombinant RNA, origin of life
- MeSH terms
- Base Sequence, Models, Genetic, Nucleic Acid Conformation, Polynucleotide Ligases, RNA, RNA, Catalytic, Directed Molecular Evolution, Evolution, Molecular
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