The nucleotide divergence at synonymous third sites between two lineag
es will increase with time since the latest common ancestor, up to som
e saturation level. The ''null-hypothesis divergence'' is defined as t
he percentage of difference predicted at synonymous third sites, allow
ing for amino acid composition and codon bias, but assuming that codon
bias is the same at all sites occupied by a given amino acid, when eq
uilibrium has been reached between forward and backward substitutions.
For two highly expressed genes, gapA and ompA, in the enterobacteria,
the estimated values of the null-hypothesis divergence are 39.3 and 3
8.15%, respectively, compared to estimated values of saturation diverg
ence of 19.0 and 25.4%. A possible explanation for this discrepancy is
that different codons for a given amino acid are favored at different
sites in the same gene.