Results are described from application of a computer program that compares the 
expected and actual incidence of CpG dinucleotides in relation to the codon 
reading frame of genes, assuming a conserved amino acid sequence and normalizing 
for the third-position incidences of C and G in the remainder of the sequence. 
Sequences encoding certain proteins showed a pronounced bias in favour of CpG in 
the (3,1) compared with the (2,3) codon position; whereas sequences encoding 
related proteins expressed to a similar extent or in the same tissue did not. We 
propose that the cases exhibiting this bias reflect a difference between the two 
strands of the DNA duplex in their susceptibility to loss of CpG dinucleotides 
by mutation. Although in vertebrates this loss of CpG dinucleotides from the 
sense strand might reflect strand-asymmetry in deamination of 5-methylcytosine 
residues, the fact that a similar CpG codon bias is found in some invertebrates 
indicates that other factor(s) must also be involved.