A single genome appears to be a cohesive community of distinct genes with common incentives. Across development, genes collaborate to build a robust and fertile individual. Across evolution, genes accumulate adaptive mutations that build an even more robust, and even more fertile, individual. The more robust and fertile the individual, the more copies of all these genes in the next generation. In this way, our genome’s distinct genes contribute to a communal good. However, much of our DNA serves no beneficial function. Most of this DNA has minimal impact on health and fertility; consequently, natural selection fails to efficiently purge it from our genome. Some of this DNA harms us, reducing our Darwinian fitness. Extensive evolutionary theory posits that this “selfish DNA” triggers adaptive evolution of the host genome to suppress selfish DNA proliferation and its deleterious impacts on fitness. My lab seeks to define the identity, molecular mechanisms, and biological consequences of such intra-genomic conflicts. In my seminar, I will describe how we exploit inter-species gene swaps to reveal antagonistic coevolution between rapidly evolving repetitive DNA and DNA repair proteins in Drosophila. Our genetic manipulations, cell biological analysis, and evolutionary genomic data suggest that DNA repair machinery must recurrently evolve to preserve genome integrity in the face of ever-changing DNA repeats. This antagonistic coevolution reminds us that our genome is not an optimized blueprint but instead an imperfect product of our evolutionary past.