The Codon Adaptation Index (CAI) is the most widespread technique for analyzing Codon usage bias

Codon usage bias

Codon usage bias refers to differences in the frequency of occurrence of synonymous codons in coding DNA. A codon is a series of three nucleotides that encodes a specific amino acid residue in a polypeptide chain or for the termination of translation .There are 64 different codons but only 20...

. As opposed to other measures of codon usage bias, such as the 'effective number of codons

Effective number of codons

Effective number of codons is a measure to study the state of codon usage biases in genes and genomes. The way that ENC is computed has obvious similarities to the computation of effective population size in population genetics...

' (Nc), which measure deviation from a uniform bias (null hypothesis), CAI measures the deviation of a given protein coding gene sequence with respect to a reference set of genes.

Rationale

Ideally, the reference set in CAI is composed of highly expressed genes, so that CAI provides an indication of gene expression level under the assumption that there is translational selection to optimize gene sequences according to their expression levels. The rationale for this is dual: highly expressed genes need to compete for resources (i.e. ribosomes)in fast-growing organisms and it makes sense for them to be also more accurately translated. Both hypotheses lead to highly expressed genes using mostly codons for tRNA species that are abundant in the cell.

Implementation

CAI is simply defined as the geometric mean of the weight associated to each codon over the length of the gene sequence (measured in codons).


For each amino acid, the weight of each of its codons, in CAI, is computed as the ration between the observed frequency of the codon (f_i) and the frequency of the synonymous codon (f_j) for that amino acid.