Codon distribution in vertebrate genes may be used to predict gene length.

I have analysed the coding regions of 96 eukaryotic genes for their use of iso-coding codons. Specific codons occur more frequently in specific positions in all members of some gene families than would be expected if codon choice was determined solely by the frequency of codon usage. In the absence of evidence a priori for selection for particular codons at particular positions, I term such co-occurring codons "coincident codons". Coincident codons are not confined to particular regions of genes, and their occurrence is not detectably linked with the location of introns in the genomic sequence. Their presence is partly but not completely explained by the exchange of sequence between similar functional genes within a species: homologous genes from different organisms also possess the same codons at some sites with greater than expected frequencies. The relative excess of coincident codons correlates well with the overall length of the genes analysed, but not with the length of mRNA or coding regions, or with qualitative features of gene structure or expression. This, and the unusual sequence environment of coincident codons, suggests that they are a feature of the overall secondary structure of the heterogeneous nuclear RNA. Such considerations suggest approaches for optimizing the expression of exogenous genes in eukaryotic systems, and for predicting the structure of genes for which only partial sequence data is available.