Using a general form of the directional mutation theory, this paper analyzes the 
effect of mutations in mutator genes on the G+C content of DNA, the frequency of 
substitution mutations, and evolutionary changes (cumulative mutations) under 
various degrees of selective constraints. Directional mutation theory predicts 
that when the mutational bias between A/T and G/C nucleotide pairs is 
equilibrated with the base composition of a neutral set of DNA nucleotides, the 
mutation frequency per gene will be much lower than the frequency immediately 
after the mutator mutation takes place. This prediction explains the wide 
variation of the DNA G+C content among unicellular organisms and possibly also 
the wide intragenomic heterogeneity of third codon positions for the genes of 
multicellular eukaryotes. The present analyses lead to several predictions that 
are not consistent with a number of the frequently held assumptions in the field 
of molecular evolution, including belief in a constant rate of evolution, 
symmetric branching of phylogenetic trees, the generality of higher mutation 
frequency for neutral sets of nucleotides, the notion that mutator mutations are 
generally deleterious because of their high mutation rates, and teleological 
explanations of DNA base composition.