Codon usage in Homo sapiens: evidence for a coding pattern on the non-coding strand and evolutionary implications of dinucleotide discrimination.

This study reports the analysis of codon usage in 35 complete Homo sapiens genes. Both codon frequency and inter-codon interference exhibit patterns of evolutionary interest. There is a significant positive correlation between the frequency with which a given codon is used and the frequency with which its complement is used. Since the frequency of appearance of the complementary codon on the coding strand is equal to the frequency of appearance of the original codon on the non-coding strand, in the same phase, the non-coding strand is found to resemble the coding strand in triplet composition. The same effect has been observed in Escherichia coli. This preference for the use of certain complementary triplets as codons suggests that the evolution of the use of the genetic code depended to some extent upon the double-stranded nature of the coding material. In addition, the effect of discrimination against the use of two dinucleotides, CpG and UpA, is observed in codon usage and also in adjacent codon interference. Codons beginning with G, or A, are unlikely to be preceded by codons ending in C, or U, respectively. Consideration of codon assignment in the genetic code together with the observed CpG infrequency suggests that the evolution of the code may have been influenced by conditions in which the use of CpG dinucleotides was unfavorable. The infrequent use of UpA dinucleotides can be explained as the result of frameshift mutation during gene evolution.