Pervasive suppressors halt the spread of selfish <i>Segregation Distorter</i> in a natural population

Abstract Meiotic drivers are selfish genetic elements that subvert Mendelian inheritance to increase their own transmission, yet they are typically found at low frequencies across natural populations. The factors that limit their spread remain unclear. The Segregation Distorter (SD) system, a selfish coadapted gene complex in Drosophila melanogaster, is an excellent model to study this paradox. SD biases its transmission by killing sperm carrying a homologous chromosome bearing a target locus, Responder (Rsp), which corresponds to satellite repeats. Such selfish killing impairs male fertility and imposes selective pressure on the host genome to evolve resistance, either by deleting Rsp copies, or acquiring unlinked suppressors. The interplay of these factors in natural populations is poorly understood. We studied the genetic factors contributing to drive strength in strains derived from a natural population of D. melanogaster from Raleigh, North Carolina known as Drosophila Genome Reference Panel (DGRP). Here we characterized the spectrum of Rsp alleles and the frequency of segregating suppressors in 90 DGRP strains. Our approach disentangles drive resistance at Rsp from suppression. Rather than loss of Rsp, we found that over half of the strains harbor suppressors located on the X chromosome or autosomes, but not the Y chromosome. The widespread presence of strong suppressors limited the resolution of our genome-wide association mapping; however, recombination analysis using a DGRP strain identified a strong X-linked suppressor to a ∼300 kb interval on the chromosome. Together, our findings suggest that pervasive, multilocus suppression constrains the spread of SD in natural populations.