Doublet preference and gene evolution.

Doublet preference analysis was carried out on coding and noncoding regions of Escherichia coli, Saccharomyces cerevisiae, and human mitochondrial and nuclear DNA. The preference pattern in 1-2 and 2-3 doublets in E. coli and S. cerevisiae correlated with that in noncoding regions. The 3-1 doublet preference in E. coli genes with low optimal codon frequency and in S. cerevisiae genes also showed a correlation with each of their noncoding doublet preference. A mechanism to explain these double preference correlations in doublet preference is presented: mutational biases, the origin of the noncoding region doublet preference, evolved so as to maintain the 1-2 and 2-3 doublet preference, which is determined by codon usage. These biases then acted on the 3-1 doublet, which was almost free of coding constraints, resulting in a similar preference in this doublet.