ArticleProceedings of the National Academy of Sciences of the United States of America2016
Codon usage is an important determinant of gene expression levels largely through its effects on transcription.
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 235 papers, 1 of them a synthesis that pooled it.
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Who cites it
235 citing papers in PubMed, 1 synthesis or guideline pooled it, 472 citations in OpenAlex.
- Synonymous but Not Silent: The Codon Usage Code for Gene Expression and Protein Folding.Annual review of biochemistry · 2021Pooled it
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- Conservation Status, Plastome Diversity, and Evolutionary Diversification of Three ArabianBiology · 2026Article
- A naturally synonymous mutation modulates an ERK-centered regulatory network to mediate thermotolerance divergence in Crassostrea oysters.Communications biology · 2026Article
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- Codon usage patterns and phylogenetic analysis of chloroplast genomes reveal evolutionary insights into Asphodelaceae species.Scientific reports · 2026Article
- Immunoinformatic-based design of a multi-epitope subunit vaccine against Ruminococcus torques using subtractive proteomics and molecular dynamics simulations.Scientific reports · 2026Article
- Complete mitochondrial genome of Laetiporus ailaoshanensis (Laetiporaceae, Basidiomycota): features, evolution, and phylogeny.BMC genomics · 2026Article
- Holostean genomes reveal evolutionary novelty in the vertebrate immunoproteasome that have implications for MHCI function.Molecular biology and evolution · 2026Article
- Comparative Codon Usage Bias of CD2AP and BACH2 Across 49 Vertebrates: Implications for Porcine Macrophage Immunity inBiology · 2026Article
- A slight mismatch between a gene's codon usage and the cellular tRNA supply is beneficial.Nature communications · 2026Article
- scLong: a billion-parameter foundation model for capturing long-range gene context in single-cell transcriptomics.Nature communications · 2026Article
- First Plastome Sequences of Two Endemic Taxa ofBiology · 2026Article
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- Efficient Expression of Lactone Hydrolase Cr2zen for Scalable Zearalenone Degradation inToxins · 2025Article
- Nuclear effects play an important role in determining codon usage-dependent human gene expression.Nature communications · 2025Article
- Coupling mechanisms coordinating mRNA translation with stages of the mRNA lifecycle.RNA biology · 2025Review
- Functional synonymous mutations and their evolutionary consequences.Nature reviews. Genetics · 2025Review
175 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Codon usage biases are found in all eukaryotic and prokaryotic genomes, and preferred codons are more frequently used in highly expressed genes. The effects of codon usage on gene expression were previously thought to be mainly mediated by its impacts on translation. Here, we show that codon usage strongly correlates with both protein and mRNA levels genome-wide in the filamentous fungus Neurospora Gene codon optimization also results in strong up-regulation of protein and RNA levels, suggesting that codon usage is an important determinant of gene expression. Surprisingly, we found that the impact of codon usage on gene expression results mainly from effects on transcription and is largely independent of mRNA translation and mRNA stability. Furthermore, we show that histone H3 lysine 9 trimethylation is one of the mechanisms responsible for the codon usage-mediated transcriptional silencing of some genes with nonoptimal codons. Together, these results uncovered an unexpected important role of codon usage in ORF sequences in determining transcription levels and suggest that codon biases are an adaptation of protein coding sequences to both transcription and translation machineries. Therefore, synonymous codons not only specify protein sequences and translation dynamics, but also help determine gene expression levels.
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