ArticleProceedings of the National Academy of Sciences of the United States of America2024
Order of amino acid recruitment into the genetic code resolved by last universal common ancestor's protein domains.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed.
- Improved gene tree inference from removing alignment errors both from focal genes and when training substitution models.Molecular biology and evolution · 2026Article
- Multilevel genomic constraints shape nuclear tRNA gene organization in plants.The Plant journal : for cell and molecular biology · 2026Article
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- The Evolution of the First Code.Genes · 2026Review
- IQ-TREE 3: phylogenomic inference software using complex evolutionary models.Molecular biology and evolution · 2026Article
- Universal paralogs provide a window into evolution before the last universal common ancestor.Cell genomics · 2026Review
- Molecular Complexity Constrained Early Amino Acid Recruitment into the Genetic Code.Genome biology and evolution · 2026Article
- Molecular Dissipative Structuring: The Fundamental Creative Force in Biology.Entropy (Basel, Switzerland) · 2026Review
- Avoiding Catastrophic Mutations Accurately Predicts Amino Acid to Codon Pairing.Journal of molecular evolution · 2026Article
- Proteins Rich in Prime Mass Residues and Their Role in Cell Biology.Evolutionary bioinformatics online · 2026Article
- An Archean atmosphere rich in sulfur biomolecules.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Reduced Amino Acid Substitution Matrices Find Traces of Ancient Coding Alphabets in Modern Day Proteins.Molecular biology and evolution · 2025Article
- The emergence of metabolisms through Earth history and implications for biospheric evolution.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Article
- Preferential survival of prebiotic metallopeptides in the presence of ultraviolet light.Chemical science · 2025Article
- Purine Chemistry in the Early RNA World at the Origins of Life: From RNA and Nucleobases Lesions to Current Key Metabolic Routes.Chembiochem : a European journal of chemical biology · 2025Review
- The effectiveness of selection in a species affects the direction of amino acid frequency evolution.bioRxiv : the preprint server for biology · 2025Article
- Permeability selection of biologically relevant membranes matches the stereochemistry of life on Earth.PLoS biology · 2025Article
- On an RNA-Membrane Protogenome.Life (Basel, Switzerland) · 2025Article
- Chemical Evolution of Life on Earth.Genes · 2025Review
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Abstract
The current "consensus" order in which amino acids were added to the genetic code is based on potentially biased criteria, such as the absence of sulfur-containing amino acids from the Urey-Miller experiment which lacked sulfur. More broadly, abiotic abundance might not reflect biotic abundance in the organisms in which the genetic code evolved. Here, we instead identify which protein domains date to the last universal common ancestor (LUCA) and then infer the order of recruitment from deviations of their ancestrally reconstructed amino acid frequencies from the still-ancient post-LUCA controls. We find that smaller amino acids were added to the code earlier, with no additional predictive power in the previous consensus order. Metal-binding (cysteine and histidine) and sulfur-containing (cysteine and methionine) amino acids were added to the genetic code much earlier than previously thought. Methionine and histidine were added to the code earlier than expected from their molecular weights and glutamine later. Early methionine availability is compatible with inferred early use of S-adenosylmethionine and early histidine with its purine-like structure and the demand for metal binding. Even more ancient protein sequences-those that had already diversified into multiple distinct copies prior to LUCA-have significantly higher frequencies of aromatic amino acids (tryptophan, tyrosine, phenylalanine, and histidine) and lower frequencies of valine and glutamic acid than single-copy LUCA sequences. If at least some of these sequences predate the current code, then their distinct enrichment patterns provide hints about earlier, alternative genetic codes.
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