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

Abstract Meiotic drivers achieve biased transmission to the next generation, often at the expense of their host. Drive is widespread and can shape the evolution of proteins, chromosome structure, and karyotype. The sperm killer Segregation Distorter (SD) in Drosophila melanogaster is a well-studied driver but like most complex drivers its mechanism remains elusive. SD is a multigene complex, frequently associated with chromosomal inversions, where the main driver locus, a truncated duplication of the gene RanGAP kills wild-type sperm containing a satellite DNA called Responder (Rsp). Functional small RNAs are frequently implicated in the mechanisms of sperm killers, and we recently showed that Rsp is a source of these RNAs. Here we use transcriptomics in two SD haplotypes to link Rsp expression and/or RNAs to drive. We found that Rsp-derived small RNAs are underrepresented in driving testes of only one of the SD haplotypes. We show that over-expressing Rsp is sufficient to reduce drive strength in the haplotype with downregulated Rsp but not the other. We therefore shed light on the mechanism of SD by making a connection between the target and the drive phenotype. Additionally, our data imply that different haplotypes of complex drivers, like SD, can vary in their mechanism. Competing Interest Statement The authors have declared no competing interest. Footnotes New RNA-seq data and analyses, additional clarification of key results, and revisions to the text and figures. The reviews and responses are posted with review commons. Data availability statement All genomic data are being deposited in NCBI’s short read archive under the accession PRJNA1375835. All code and data underlying analyses in the manuscript will be available in Dryad (https://doi.org/10.5061/dryad.v9s4mw792) and code are available on GitHub (https://github.com/LarracuenteLab/SD-RNAseq).