codonusage

Codon usage refers to the frequencies with which synonymous codons are used to encode amino acids in protein-coding genes. In many organisms, the usage of synonymous codons is not uniform, a phenomenon known as codon usage bias. Bias can vary among organisms, among genes within a genome, and even within a gene, and reflects a balance between mutational processes, selection for translation efficiency and accuracy, and other constraints.

Common metrics to quantify codon usage include relative synonymous codon usage (RSCU), the effective number of codons (ENC), and the codon adaptation index (CAI). RSCU compares observed codon frequencies to expected frequencies under equal usage of synonymous codons; ENC summarizes overall bias on a 20-61 scale; CAI evaluates how well a gene's codons match a reference set of highly expressed genes. tRNA-based indices like the tAI also exist, incorporating wobble pairing and tRNA abundance.

Factors shaping codon usage include genomic GC content, especially at the third codon position (GC3), gene expression levels, tRNA gene copy numbers and charging, translational selection for speed and accuracy, and mutational biases. Horizontal gene transfer and regional mutation pressure can also alter codon patterns. Selection tends to favor codons matched to abundant tRNAs in highly expressed genes.

Applications include optimizing gene sequences for heterologous expression, improving protein yield in recombinant systems, and studying molecular evolution and genome organization. Analyses of codon usage are performed with various software tools and databases, such as Codon Usage Databases and genome-specific codon usage tables. These resources support comparative analyses, gene design, and exploration of translational constraints across species.