Strain variation identifies a neural substrate for behavioral evolution in Drosophila

Sexual selection acts on heritable differences within species, driving the parallel diversification of signal production in one sex and behavioral responses in the other. This coevolution implies that sensory preferences are themselves variable traits, yet the neural basis of such variation remains unclear. Here, we identify striking strain-specific differences in Drosophila melanogaster male mate preferences that arise from differential sensitivity to heterospecific female pheromones. We map this variation to an ascending inhibitory pathway targeting a central circuit node known to dynamically pattern courtship. Inhibitory circuits thus emerge as a key locus for shaping mate discrimination via transient suppression of a male’s pursuit. Our findings highlight how variation within sensory circuitry serves as a substrate for selection, fueling the evolution of reproductive barriers between species. RNA-seq profiling of male foreleg tissue from selective (CO13N, CS-CO13N hybrid) and promiscuous (CS, RG11N) strains of D. melanogaster.