Scaling of mutational effects in models for pleiotropy.

Mutation-selection models provide a framework to relate the parameters of microevolution to properties of populations. Like all models, these must be subject to test and refinement in light of experiments. The standard mutation-selection model assumes that the effects of a pleiotropic mutation on different characters are uncorrelated. As a consequence of this assumption, mutations of small overall effect are suppressed. For strong enough pleiotropy, the result is a nonvanishing fraction of a population with the "perfect" phenotype. However, experiments on microorganisms and experiments on protein structure and function contradict the assumptions of the standard model, and Kimura's observations of heterogeneity within populations contradict its conclusions. Guided by these observations, we present an alternative model for pleiotropic mutations. The new model allows mutations of small overall effect and thus eliminates the finite fraction of the population with the perfect phenotype.