The zebrafish will be used as a model system to estimate, for the first time, the average genetic properties of fitness mutations in a vertebrate. Zebrafish are ideal for this study because of the unique cytological techniques that have been developed for this species. Fish with identical genetic backgrounds will be produced that have either no mutations, are homozygous for induced mutations, or are heterozygous for exactly the same mutations. Comparison of the fitness of these fish will provide a novel way to estimate the average dominance of deleterious mutations, and similar manipulations will reveal whether mutations at different loci interact in a synergistic fashion.
The use of a vertebrate in this work is important since current attempts to evaluate the significance of mutation in humans, domesticated animals, and endangered species rely largely on extrapolation from data on flies. The properties of spontaneous mutations influence a number of processes of theoretical and practical importance, including the maintenance of adaptive genetic variation essential for population responses to natural selection and the accumulation of deleterious load that poses a significant risk of extinction for small populations.
