ArticleAmerican journal of human genetics2020
Natural Selection Shapes Codon Usage in the Human Genome.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 87 citations in OpenAlex.
- Synonymous codon usage shapes ERα function through specialized translational programs during breast cancer progression.Oncogene · 2026Article
- Linking somatic mutations in cancer to the electronic properties of DNA.BMC genomics · 2026Article
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- TRMT6/TRMT61A-mediated tRNA mCellular & molecular biology letters · 2026Article
- Functional synonymous mutations and their evolutionary consequences.Nature reviews. Genetics · 2025Review
- NSUN2-tRNACellular & molecular biology letters · 2025Article
- A New Comparative Framework for Estimating Selection on Synonymous Substitutions.Molecular biology and evolution · 2025Article
- Diverse ancestral representation improves genetic intolerance metrics.Nature communications · 2025Article
- Genome-wide prediction of dominant and recessive neurodevelopmental disorder-associated genes.American journal of human genetics · 2025Article
- Interpreting mammalian synonymous site conservation in light of the unwanted transcript hypothesis.Nature communications · 2025Article
- A new comparative framework for estimating selection on synonymous substitutions.bioRxiv : the preprint server for biology · 2025Article
- The De Novo Emergence of Two Brain Genes in the Human Lineage Appears to be Unsupported.Journal of molecular evolution · 2025Article
- Link Between Individual Codon Frequencies and Protein Expression: Going Beyond Codon Adaptation Index.International journal of molecular sciences · 2024Article
- Codon Bias of theInternational journal of molecular sciences · 2024Article
- Comparative Analysis of Codon Usage Bias in SixInternational journal of molecular sciences · 2024Article
- VP1 is the primary determinant of neuropathogenesis in a mouse model of enterovirus D68 acute flaccid myelitis.Journal of virology · 2024Article
- NeMu: a comprehensive pipeline for accurate reconstruction of neutral mutation spectra from evolutionary data.Nucleic acids research · 2024Article
- Intraspecific and interspecific variations in the synonymous codon usage in mitochondrial genomes of 8 pleurotus strains.BMC genomics · 2024Article
- Article
- Systematic analysis of the codon usage patterns of African swine fever virus genome coding sequences reveals its host adaptation phenotype.Microbial genomics · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synonymous codon usage has been identified as a determinant of translational efficiency and mRNA stability in model organisms and human cell lines. However, whether natural selection shapes human codon content to optimize translation efficiency is unclear. Furthermore, aside from those that affect splicing, synonymous mutations are typically ignored as potential contributors to disease. Using genetic sequencing data from nearly 200,000 individuals, we uncover clear evidence that natural selection optimizes codon content in the human genome. In deriving intolerance metrics to quantify gene-level constraint on synonymous variation, we discover that dosage-sensitive genes, DNA-damage-response genes, and cell-cycle-regulated genes are particularly intolerant to synonymous variation. Notably, we illustrate that reductions in codon optimality in BRCA1 can attenuate its function. Our results reveal that synonymous mutations most likely play an underappreciated role in human variation.
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Registered trials
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