It has been shown previously that the synonymous substitution rate bet
ween Escherichia coli and Salmonella typhimurium is lower in highly th
an in weakly expressed genes, and it has been suggested that this is d
ue to stronger selection for translational efficiency in highly expres
sed genes as reflected in their greater codon usage bias. This hypothe
sis is tested here by comparing the substitution rate in codon familie
s with different patterns of synonymous codon use. It is shown that th
e decline in the substitution rate across expression levels is as grea
t for codon families that do nor appear to be subject to selection for
translational efficiency as for those that are. This implies that sel
ection on translational efficiency is not responsible for the decline
in the substitution rate across genes. It is argued that the most like
ly explanation for this decline is a decrease in the mutation rate. It
is also shown that a simple evolutionary model in which synonymous co
don use is determined by a balance between mutation, selection for an
optimal codon, and genetic drift predicts that selection should have l
ittle effect on the substitution rate in the present case.