The general focus of this research is to test the hypothesis that different mitochondrial genomes affect the reproductive rate or "fitness" of the fruit fly Drosophila melanogaster. The research will employ experimental population cages where flies carrying different mitochondrial DNAs (mtDNAs) are competed against one another to determine whether certain mitochondrial genotypes have consistent reproductive advantages over other genotypes. The experiments will involve genetic crosses to construct strains of flies that have the same nuclear chromosomes but differ only in their mtDNAs. Several pairwise tests of competitive ability will be conducted between strains of flies from different populations. The populations have been chosen so that the pairwise tests will involve strains of flies with little, moderate and large amounts of DNA sequence difference between the competing mitochondrial genomes. This should provide a test of the effect of DNA sequence difference on the strength of the fitness different between strains. The research also involves a complementary set of experiments to test the "fitness" of different mtDNAs inside cells. Using a microinjection technique to transplant intact mitochondria between strains of fruit flies, one can create a miniature "population cage" inside the reproductive cells of female flies. By creating reproductive cells with mixtures of different mtDNAs, one can test the hypothesis that different mitochondrial genomes have an advantage in inheritance from mother to offspring. This approach will be employed with the same strains of flies used in the population cage experiments described above. This "two-level" approach to the study of mtDNA variation will provide information on the functional significance of naturally occurring variation in mtDNA and serve as a model system to study the coevolution of nuclear and mitochondrial genomes. Furthermore, this research will test the critical assumption for many studies of population dynamics that mtDNA variation is neutral.