The genetics and evolution of the Winters sex-ratio in Drosophila

Sex chromosome meiotic drive elements are selfish genes that increase in frequency in populations due to their transmission ratio advantage, causing skews in population sex ratios. Suppressors of drivers are strongly selected to restore Fisherian sex ratios. We characterize the structure, function, and evolution of an X-linked sex ratio distorter in Drosophila called the Winters sex-ratio which evolved in the ancestor of D. simulans, D. mauritiana, and D. sechellia between 2.3 million and 250,000 years ago. Distortion is caused by Distorter on the X (Dox), a gene that was created through the duplication of Mother of Dox (MDox), which is 70 kilo bases distal to Dox. Dox causes skewed progeny sex ratios by disrupting the development of Y-bearing sperm through abnormal chromosome condensation and nuclear elongation. A dominant suppressor gene, Not Much Yang (Nmy) evolved on chromosome 3R as a retrotransposed copy of Dox. We collect molecular population genetic data from D. simulans and D. mauritiana, sister species who diverged 250,000 years ago. Through structural analysis of gene regions, we show that Dox and MDox have a single origin and that each arose through non-allelic homologous recombination, mediated by 360bp satellite DNA repeat elements that flank the genes. D. simulans is polymorphic for all three genes whereas D. mauritiana has fixed MDox and Nmy, but is polymorphic for Dox. Coalescent modeling of positive selection indicates that selective sweeps have occurred at all three genes in North American populations of D. simulans in the last 100,000 years. In addition, the derived alleles in D. simulans show reduced diversity relative to ancestral null loci, which lack the gene insertions. Phylogenetic analysis is consistent with recurrent selective sweeps at Dox and Nmy in D. simulans. The high frequency of Nmy in natural populations of D. simulans likely silences Dox, and the gene has accumulated loss-of-function mutations. In contrast, Dox and MDox remain completely undifferentiated from each other in D. mauritiana, indicating that Dox has not been neo- or sub-functionalized and may be eventually lost due to genetic drift.