Small population sizes characteristic of endangered species have several genetic consequences that can magnify the probability of extinction. This proposal is concerned primarily with the loss of fitness due to the accumulation of mildly deleterious mutations. The effectiveness of natural selection in eliminating such genes is reduced when a population declines in size, and the consequent build-up of mutation load can cause a further reduction in population size. This synergistic effect between chance effects of small population size and deleterious mutation leads to an extinction process called a mutational melt- down. Preliminary theoretical results demonstrate clearly that such a process can greatly increase the vulnerability to extinction within a fairly narrow time frame. Dr. Lynch proposes to pursue the theory further in a number of directions: the influence of the mode of density-dependent regulation of population size, the form of the fitness function, the consequences of fertility vs. viability mutations, melt-downs in organelle genomes, and the additional contribution of mutation load in the base population. This work should greatly enhance understanding of processes at the interface of population dynamics and population genetics, an area of special relevance to conservation biology that has scarcely been touched in previous studies. Application of the theory to specific problems will require quantitative information on the recurrent mutation load, which to date is only available for Drosophila. Such data are difficult to acquire, but are obtainable from self-fertilized lines maintained by single-seed descent. Dr. Lynch will perform a series of very large, long-term experiments to acquire data on the input of mutations for fitness characters, using the rapid- cycling plant Arabidopsis as a model system. The statistical theory for the analysis of data and for the optimal design of experiments has been developed.