Genetic variation within populations is ultimately the source of all evolutionary change. Allozyme data were for the most part insufficient for determining the relative importance of mutation, genetic drift, recombination, and natural selection in determining the distribution of genetic variation in nature. DNA data are qualitatively different in that they provide a history of genetic variation in natural populations, thereby allowing one to make inferences regarding the type of selection acting on a locus (i.e., purifying, directional, balancing) and the variants within a locus which are a target of selection. The work outlined in this proposal is an attempt to understand patterns of selection over the distal half of the X chromosome in Drosophila malanogaster and Drosophila simulans. Previous data suggest the allozyme polymorphism at phosphogluconate dehydrogenase (pgd) is a target of selection in D. manlanogaster. It is proposed to build on these data with a molecular analysis of population variation at pgd. The molecular data will allow determination of the influence of selection and recombination on the distribution of variation at this locus and localize specific variants on which selection acts. This X-linked gene is located near the telomere, a region known to have low recombination rates. Theoretical results and preliminary data suggest that a significant fraction of DNA variation in the region could be influenced by genetic "hitchhiking" associated with the fixation of advantageous mutants. Thus, pgd may have had a complex history, with variation influenced by local and regional phenomena. Therefore, in addition to detailed study of pgd, DNA variation at several gene regions on either side of pgd will be measured in order to place the pgd data in a large context and determine the impact of selective substitutions on DNA variation over the distal portion of the X chromosome.
