A mechanism for the association of amino acids with their codons and the origin of the genetic code
Open accessAbstract
The genetic code has certain regularities that have resisted mechanistic interpretation. These include strong correlations between the first base of codons and the precursor from which the encoded amino acid is synthesized and between the second base of codons and the hydrophobicity of the encoded amino acid. These regularities are even more striking in a projection of the modern code onto a simpler code consisting of doublet codons encoding a set of simple amino acids. These regularities can be explained if, before the emergence of macromolecules, simple amino acids were synthesized in covalent complexes of dinucleotides with α-keto acids originating from the reductive tricarboxylic acid cycle or reductive acetate pathway. The bases and phosphates of the dinucleotide are proposed to have enhanced the rates of synthetic reactions leading to amino acids in a small-molecule reaction network that preceded the RNA translation apparatus but created an association between amino acids and the first two bases of their codons that was retained when translation emerged later in evolution.
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The GNC code was promoted by the pre-tRNA/pre-mRNA interaction and coevolution.
“Perhaps GNC code was promoted by the pre-tRNA/pre-mRNA interaction and coevolution [116,117] (Figure 5A).”
From The Origin of Prebiotic Information System in the Peptide/RNA World: A Simulation Model of the Evolution of Translation and the Genetic Code (2019) · cites this paper as [117]
The origin of biomolecular machinery likely centered around the tRNA-amino acid alliance, both being ancient molecules in the prebiotic environment.
“The origin of biomolecular machinery likely centered around the tRNA-amino acid alliance, both being ancient molecules in the prebiotic environment [74,117].”
From The Origin of Prebiotic Information System in the Peptide/RNA World: A Simulation Model of the Evolution of Translation and the Genetic Code (2019) · cites this paper as [117]
The intricate and universal relationship between RNA and amino acids that led to the genetic code seems likely to have been a very early development in the evolution of life.
“Indeed, the intricate and universal relationship between RNA and amino acids that led to the genetic code seems likely to have been a very early development in the evolution of life (e.g., Copley et al., 2005).”
From The Astrobiology Primer v2.0 (2016) · cites this paper as Copley et al., 2005
Cites
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The molecular basis for the genetic code.
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ORIGINS OF THE GENETIC CODE: The Escaped Triplet Theory
Yarus, M., Caporaso, J. G., & Knight, R. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133119 · Cited by 166 · see citing works
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On the origin of biochemistry at an alkaline hydrothermal vent
Martin, W., & Russell, M. J. (2007) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2006.1881 · Cited by 771 · see citing works
On the origin of genomes and cells within inorganic compartments
Koonin, E. V., & Martin, W. (2005) · Trends in Genetics · doi:10.1016/j.tig.2005.09.006 · Cited by 406 · see citing works
Nonenzymatic Metabolic Reactions and Life’s Origins
Muchowska, K. B., Varma, S. J., & Moran, J. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00191 · Cited by 317 · see citing works
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Wolf, Y. I., & Koonin, E. V. (2007) · Biology Direct · doi:10.1186/1745-6150-2-14 · Cited by 235 · see citing works
The origin of the RNA world: Co-evolution of genes and metabolism
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Self-citationThe Future of Origin of Life Research: Bridging Decades-Old Divisions
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Domagal-Goldman, S. D., Wright, K. E., Domagal-Goldman, S. D., Wright, K. E., Adamala, K., Arina de la Rubia, L., Bond, J., Dartnell, L. R., Goldman, A. D., Lynch, K., et al. (2016) · Astrobiology · doi:10.1089/ast.2015.1460 · Cited by 136 · see citing works
“Indeed, the intricate and universal relationship between RNA and amino acids that led to the genetic code seems likely to have been a very early development in the evolution of life (e.g., Copley et al., 2005).”
Chatterjee, S., & Yadav, S. (2019) · Life · doi:10.3390/life9010025 · Cited by 80 · see citing works
“Various authors have suggested that the original amino acid-binding motifs could have been the actual codons rather than anticodons [117,119].”
BackgroundExceptional error minimization in putative primordial genetic codes
Novozhilov, A. S., & Koonin, E. V. (2009) · Biology Direct · doi:10.1186/1745-6150-4-44 · Cited by 37 · see citing works
- Authors
- Copley, S. D., Smith, E., & Morowitz, H. J.
- Affiliations
- Santa Fe Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-03-11
- Volume
- 102
- Issue
- 12
- Pages
- 4442-4447
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC555468
- OpenAlex
- W2072759169
- Cited by
- 134
- References
- 3
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 10 · 2020: 6 · 2019: 22 · 2018: 5 · 2016: 4 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 7
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Aeronautics and Space Administration
- John Templeton Foundation
- Santa Fe Institute
- 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
- origin of the genetic code, amino acid synthesis, dinucleotides, α-keto acids, reductive tricarboxylic acid cycle, amino acid hydrophobicity, prebiotic chemistry, origin of translation
- MeSH terms
- Amino Acids, Codon, Decarboxylation, Decision Trees, Genetic Code, Keto Acids, Models, Biological, Models, Genetic, Phosphorylation, Evolution, Molecular, Pyruvic Acid
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