ArticleProceedings of the National Academy of Sciences of the United States of America2014
Reducing the genetic code induces massive rearrangement of the proteome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Proteomic stress response by a novel methanogen enriched from the Great Salt Lake.Microbiology spectrum · 2026Article
- Methanogenic archaea encoding Pyrrolysine maintain ambiguous amber codon usage.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- High-fidelity and differential nonsense suppression in live cells and a frontotemporal dementia allele with human transfer RNAs.Nucleic acids research · 2025Article
- Cracking the Code: Reprogramming the Genetic Script in Prokaryotes and Eukaryotes to Harness the Power of Noncanonical Amino Acids.Chemical reviews · 2024Review
- Physiological and transcriptomic response to methyl-coenzyme M reductase limitation inApplied and environmental microbiology · 2024Article
- Biosynthesis, Engineering, and Delivery of Selenoproteins.International journal of molecular sciences · 2023Review
- Update of the Pyrrolysyl-tRNA Synthetase/tRNAJournal of bacteriology · 2023Review
- Elucidating miRNA Function in Cancer Biology via the Molecular Genetics' Toolbox.Biomedicines · 2022Review
- Transfer RNAs: diversity in form and function.RNA biology · 2021Review
- Rewiring protein synthesis: From natural to synthetic amino acids.Biochimica et biophysica acta. General subjects · 2017Review
- Efforts and Challenges in Engineering the Genetic Code.Life (Basel, Switzerland) · 2017Review
- Genetic code flexibility in microorganisms: novel mechanisms and impact on physiology.Nature reviews. Microbiology · 2015Review
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
Abstract
Expanding the genetic code is an important aim of synthetic biology, but some organisms developed naturally expanded genetic codes long ago over the course of evolution. Less than 1% of all sequenced genomes encode an operon that reassigns the stop codon UAG to pyrrolysine (Pyl), a genetic code variant that results from the biosynthesis of Pyl-tRNA(Pyl). To understand the selective advantage of genetically encoding more than 20 amino acids, we constructed a markerless tRNA(Pyl) deletion strain of Methanosarcina acetivorans (ΔpylT) that cannot decode UAG as Pyl or grow on trimethylamine. Phenotypic defects in the ΔpylT strain were evident in minimal medium containing methanol. Proteomic analyses of wild type (WT) M. acetivorans and ΔpylT cells identified 841 proteins from >7,000 significant peptides detected by MS/MS. Protein production from UAG-containing mRNAs was verified for 19 proteins. Translation of UAG codons was verified by MS/MS for eight proteins, including identification of a Pyl residue in PylB, which catalyzes the first step of Pyl biosynthesis. Deletion of tRNA(Pyl) globally altered the proteome, leading to >300 differentially abundant proteins. Reduction of the genetic code from 21 to 20 amino acids led to significant down-regulation in translation initiation factors, amino acid metabolism, and methanogenesis from methanol, which was offset by a compensatory (100-fold) up-regulation in dimethyl sulfide metabolic enzymes. The data show how a natural proteome adapts to genetic code reduction and indicate that the selective value of an expanded genetic code is related to carbon source range and metabolic efficiency.
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