Disruption of small RNAs and mechanistic variation in <i>Segregation Distorter—</i> a sperm-killing drive system in <i>Drosophila melanogaster</i>

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 <i>Segregation Distorter</i> ( <i>SD</i> ) found in natural populations of <i>Drosophila melanogaster</i> is one of the best studied drivers. <i>SD</i> is a multigene complex, frequently associated with chromosomal inversions, that kills sperm carrying a large block of satellite DNA called <i>Responder</i> ( <i>Rsp</i> ). We do not know the mechanism of drive or the role of the target satellite. Here we use transcriptomics in two <i>SD</i> haplotypes that diVer in their inversions to link <i>Rsp</i> expression to drive. We found that <i>Rsp</i> -derived small RNAs are underrepresented in driving testes of one <i>SD</i> haplotype. We used genetic experiments to show that over expressing <i>Rsp</i> was suVicient to reduce drive strength in the haplotype with the <i>Rsp</i> smRNA phenotype. We therefore shed light on mechanism of <i>SD</i> by making a connection between the target and driver. Our study also suggests that complex drivers, like <i>SD</i> , can vary in their mechanism of targeting or sperm killing.