The objective of the proposed study is to analyze the intraspecific and interspecific variation of nucleotide sequences of a phenotypically monomorphic locus to determine the important evolutionary forces that generate and maintain nucleotide diversity in natural populations. Nucleotide diversity is the ultimate source of phenotypic variation which allows organisms to adapt to new environmental challenges in natural populations such as acquiring disease resistance. Thus, it is important to understand the evolutionary forces that modulate the levels of genetic variation in natural populations. In addition, the evolutionary dynamics of a genetic locus that is phenotypically simple must be understood before the evolutionary forces that shape the pattern and organization of nucleotide diversity of phenotypically complex loci can be ascertained. The proposed study will sample the nucleotide diversity of 100 nucleotide sequences of the alcohol dehydrogenase (Adh) region, a phenotypically monomorphic locus, from five natural populations of Drosophila pseudoobscura and one population of D. persimilis to test whether this locus fits the predictions of the neutral theory of molecular evolution. A phenotypically monomorphic locus should behave according to the predictions of the neutral theory in the absence of other evolutionary forces such as natural selection. Any departures from the predictions of the neutral model seen in the Adh region of D. pseudoobscura will suggest that the action of natural selection may shape the pattern and organization of nucleotide diversity at a phenotypically monomorphic locus.