ArticleProceedings of the National Academy of Sciences of the United States of America2016
Emergent rules for codon choice elucidated by editing rare arginine codons in Escherichia coli.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Cell-Free Approach for Non-canonical Amino Acids Incorporation Into Polypeptides.Frontiers in bioengineering and biotechnology · 2020Pooled it
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- Mechanistic and evolutionary insights into a family of aminoacyl-tRNA deacylases that protects against canavanine toxicity.Nucleic acids research · 2025Article
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- Recent advances in genome-scale engineering inEngineering microbiology · 2024Review
- Strategies to identify and edit improvements in synthetic genome segments episomally.Nucleic acids research · 2023Article
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- Investigation of Genome Biology by Synthetic Genome Engineering.Bioengineering (Basel, Switzerland) · 2023Review
- SURE editing: combining oligo-recombineering and programmable insertion/deletion of selection markers to efficiently edit the Mycoplasma pneumoniae genome.Nucleic acids research · 2022Article
- Multiplex base editing to convert TAG into TAA codons in the human genome.Nature communications · 2022Article
- Current trends in biopharmaceuticals production in Escherichia coli.Biotechnology letters · 2022Review
- Improving the Efficiency and Orthogonality of Genetic Code Expansion.Biodesign research · 2022Review
- The transcriptional landscape of a rewritten bacterial genome reveals control elements and genome design principles.Nature communications · 2021Article
- Reprogramming the genetic code.Nature reviews. Genetics · 2021Review
- Recombineering and MAGE.Nature reviews. Methods primers · 2021Article
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Authors and funding
12 authors.
Funding
Abstract
The degeneracy of the genetic code allows nucleic acids to encode amino acid identity as well as noncoding information for gene regulation and genome maintenance. The rare arginine codons AGA and AGG (AGR) present a case study in codon choice, with AGRs encoding important transcriptional and translational properties distinct from the other synonymous alternatives (CGN). We created a strain of Escherichia coli with all 123 instances of AGR codons removed from all essential genes. We readily replaced 110 AGR codons with the synonymous CGU codons, but the remaining 13 "recalcitrant" AGRs required diversification to identify viable alternatives. Successful replacement codons tended to conserve local ribosomal binding site-like motifs and local mRNA secondary structure, sometimes at the expense of amino acid identity. Based on these observations, we empirically defined metrics for a multidimensional "safe replacement zone" (SRZ) within which alternative codons are more likely to be viable. To evaluate synonymous and nonsynonymous alternatives to essential AGRs further, we implemented a CRISPR/Cas9-based method to deplete a diversified population of a wild-type allele, allowing us to evaluate exhaustively the fitness impact of all 64 codon alternatives. Using this method, we confirmed the relevance of the SRZ by tracking codon fitness over time in 14 different genes, finding that codons that fall outside the SRZ are rapidly depleted from a growing population. Our unbiased and systematic strategy for identifying unpredicted design flaws in synthetic genomes and for elucidating rules governing codon choice will be crucial for designing genomes exhibiting radically altered genetic codes.
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