ArticleCell systems2016
RNA Structural Determinants of Optimal Codons Revealed by MAGE-Seq.
Article in Cell systems, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 81 citations in OpenAlex.
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- Bacterial gene 5' ends have unusual mutation rates that can mislead tests of selection.PLoS biology · 2025Article
- Long-range mRNA folding shapes expression and sequence of bacterial genes.bioRxiv : the preprint server for biology · 2025Article
- Why AGG is associated with high transgene output: passenger effects and their implications for transgene design.NAR genomics and bioinformatics · 2025Article
- Improving the generalization of protein expression models with mechanistic sequence information.Nucleic acids research · 2025Article
- Sequence modeling and design from molecular to genome scale with Evo.Science (New York, N.Y.) · 2024Article
- A long-context language model for deciphering and generating bacteriophage genomes.Nature communications · 2024Article
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- Rapid protein evolution by few-shot learning with a protein language model.bioRxiv : the preprint server for biology · 2024Article
- Reversions mask the contribution of adaptive evolution in microbiomes.bioRxiv : the preprint server for biology · 2024Article
- Systematic enhancement of protein crystallization efficiency by bulk lysine-to-arginine (KR) substitution.Protein science : a publication of the Protein Society · 2024Article
- Efficient evolution of human antibodies from general protein language models.Nature biotechnology · 2024Article
- Competition-driven eco-evolutionary feedback reshapes bacteriophage lambda's fitness landscape and enables speciation.Nature communications · 2024Article
- ProteinGym: Large-Scale Benchmarks for Protein Design and Fitness Prediction.bioRxiv : the preprint server for biology · 2023Article
- Article
- Large-scale analysis of mRNA sequences localized near the start and amber codons and their impact on the diversity of mRNA display libraries.Nucleic acids research · 2023Article
- Resolving Deleterious and Near-Neutral Effects Requires Different Pooled Fitness Assay Designs.Journal of molecular evolution · 2023Article
- Revealing determinants of translation efficiency via whole-gene codon randomization and machine learning.Nucleic acids research · 2023Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Synonymous codon choices at the beginning of genes optimize 5' RNA structures for enhanced translation initiation, but less is known about mechanisms that drive codon optimization downstream within the gene. To understand what determines codon choices across a gene, we generated 12,726 in situ codon mutants in the Escherichia coli essential gene infA and measured their fitness by combining multiplex automated genome engineering mutagenesis with amplicon deep sequencing (MAGE-seq). Correlating predicted 5' RNA structure with fitness revealed that codons even far from the start of the gene are deleterious if they disrupt the native 5' RNA conformation. These long-range structural interactions generate context-dependent rules that constrain codon choices beyond intrinsic codon preferences. Genome-wide RNA folding predictions confirm that natural codon choices far from the start codon are optimized in part to prevent disruption of native structures near the 5' UTR. Our results shed light on natural codon distributions and should improve engineering of gene expression for synthetic biology applications.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.