In Drosophila, studies of reproductive protein evolution have shown evidence of elevated levels of adaptive evolution compared to the genomic background. Few, however, have studied the molecular evolution of genes involved in the regulation of the germline stem cell (GSC). My dissertation examines the population genetics of a larger class of genes regulating the GSC, and using a comparative genomic approach to test the hypothesis that infection by the endosymbiotic bacteria Wolbachia pipientis is a selective driver causing the rapid evolution at some of the GSC genes. First, following up on previous observations of adaptive evolution of several GSC genes (particularly bam and bgcn) in D. melanogaster and D. simulans, I have studied the population genetics of these genes in D. ananassae because this species also shows evidence of infection by W. pipientis. However, despite what I show to be a comparable W. pipientis infectious history among D. melanogaster, D. simulans, and D. ananassae; neither bam nor bgcn were evolving under positive selection in D. ananassae. Thus, a simple W. pipientis driven rapid evolution at these genes was not supported by my results. Second, I expanded the population genetic analysis of GSC genes to include all genes that show evidence of involvement in D. melanogaster GSC regulation. Results for these were then compared to genes involved in neural stem cell regulation. My results showed that both germline and neural stem cell are enriched for genes with evidence of recent selective sweeps, but not long-term recurrent adaptive evolution, compared to a randomly chosen group of control genes. Further, overall inferences of rates of adaptive fixation for germline and neural stem cells showed levels comparable to most classes of genes for D. melanogaster and D. simulans. Lastly, I have used whole-genome sequencing to gain deeper insight into the evolutionary history of W. pipientis infecting D. ananassae. D. ananassae has unique evidence of the whole genome of W. pipientis integrated into the host nuclear genome. My results showed that the infectious W. pipientis genome has a stable maternally inherited evolutionary history while the integrated W. pipientis genome had become a potentially functionless pseudogenome.