This project is concerned with the long-term constraints on the rate of phenotypic evolution, particularly with the interaction of mutation and random genetic drift. Recent theoretical work has clarified the important contribution that polygenic mutation makes to the divergence of inbred lines, the response to long-term directional selection programs, and the maintenance of genetic variation under stabilizing selection. However, the practical utility of this theory is severely limited by a lack of rigorous. information on the properties of polygenic mutation. Using three model systems (the microcrustacean Daphnia, the snail Lymnaea, and corn), we plan to initiate long-term mutation-accumulation experiments in order to: 1) obtain estimates for the mutational rate of input of genetic variance (VM) and extent of dominance and pleiotropic effects of new mutations, and 2) test the hypotheses that the rate of polygenic mutation depends on generation time, frequency of meiosis, age of expression of characters, and genetic background. The proposed species and experimental protocols have been specifically selected in order to avoid the problems that have marred previous attempts to measure the properties of polygenic mutation and to help reveal whether existing estimates of VM are biased. In conjunction with the empirical work, analytical and numerical studies will be performed in order to develop quantitative genetic models that incorporate the joint interaction of finite population size, polygenic mutation, and selection. The sensitivity of the theoretical predictions to dominance, linkage, and pleiotropy will be evaluated. The long-term practical goals of the study are to provide the quantitative information necessary to: 1) predict the expected stability of asexual and homozygous lines that are becoming increasingly utilized in biomedical research, 2) determine the optimal designs of long-term selection programs and genetic conservation programs.