The primary focus of this project is the investigation of the relative roles of mutation, recombination, genetic drift and natural selection in shaping the levels of genetic variation observed at the DNA level. Specific experiments look for evidence of migration and population subdivision in the geographic distribution of DNA sequence variation at the Adh locus in Drosophila melanogaster. Several experiments address the fundamental question: what is the quantity and quality of molecular population genetic variation? To obtain a general answer many loci (White, yellow to achete, g-6-phd, forked, vermilion, suppressor of forked and forked) in natural populations of Drosophila have been surveyed. A specific question in these and comparative studies with other species is the consequence of large differences in the amounts of crossing over per kilobase on the molecular genetic variation. The hypothesis that environmental heavy metals have selected for duplication of the metallothionein gene in natural populations is being tested by comparing the frequencies of these variants in locations with large differences in lead and cadmium pollution.