Why are phenotypic mutation rates much higher than genotypic mutation rates?

The evolution of genotypic mutation rates has been investigated in numerous theoretical and experimental studies. Mutations, however, occur not only when copying DNA, but also when building the phenotype, especially when translating and transcribing DNA to RNA and protein. Here we study the effect of such phenotypic mutations. We find a maximum phenotypic mutation rate, umax, that is compatible with maintaining a certain function of the organism. This may be called a phenotypic error threshold. In particular, we find a minimum phenotypic mutation rate, umin, with the property that there is (nearly) no selection pressure to reduce the rate of phenotypic mutations below this value. If there is a cost for lowering the phenotypic mutation rate, then umin is close to the optimum phenotypic mutation rate that maximizes the fitness of the organism. In our model, there is selective pressure to decrease the rate of genotypic mutations to zero, but to decrease the rate of phenotypic mutations only to a positive value. Despite its simplicity, our model can explain part of the huge difference between genotypic and phenotypic mutation rates that is observed in nature. The relevant data are summarized.