Abstract
Meiotic drivers achieve biased transmission to the next generation, often at the expense of their host. Drive is widespread in nature and can shape the evolution of genomes and species. Many drive systems target repetitive genome regions, but we know little about their mechanisms. The sperm-killing drive system Segregation Distorter ( SD ) found in natural populations of Drosophila melanogaster is one of the best studied drivers. SD is a multigene complex, frequently associated with chromosomal inversions, that kills sperm carrying a large block of satellite DNA called Responder ( Rsp ). We do not know the mechanism of drive or the role of the target satellite. Here we use transcriptomics in two SD haplotypes that diVer in their inversions to link Rsp expression to drive. We found that Rsp -derived small RNAs are underrepresented in driving testes of one SD haplotype. We used genetic experiments to show that over expressing Rsp was suVicient to reduce drive strength in the haplotype with the Rsp smRNA phenotype. We therefore shed light on mechanism of SD by making a connection between the target and driver. Our study also suggests that complex drivers, like SD , can vary in their mechanism of targeting or sperm killing.