[Analysis of apolipoprotein gene family in codon space--non-random selection of nucleotide changes in evolution]

The choice of nucleotide changes in DNA evolution can be either selectively neutral or biased. To study how apolipoprotein gene selects the nucleotide substitutions in the course of evolution, a codon space is constructed in which its DNA sequence can be mapped as a matrix of nucleotide frequencies in three codon positions. Accordingly, a number of methods that measure the nonrandomness of nucleotide distribution in codon space are developed based on maximum entropy techniques to define the nature of nucleotide change selection in evolution. By these methods, we demonstrated that the nucleotide composition in 1st and 3rd codon position of apolipoprotein genes is highly nonrandom, which appears to be a result of non-neutral selection of codon positions by adenosine and thymidine. In addition, this paper is also concerned in the divergence of synonymos codon usage and its correlation to taxonomic distances among species. As a result, a codon usage clock was reported in apolipoprotein A-I. Our studies suggest that non-random selection of nucleotide changes in codon space may represent an evolutionary characteristics of apolipoprotein genes.