Spontaneous Emergence and Turnover of the Sex-Determining Locus

Anisogamy is nearly universal across multicellular organisms, yet how two discrete sexes arise in genomes with many recombining autosomal loci remains unresolved. Classic models show that disruptive selection on gamete size can drive anisogamy, but their single-locus assumptions conflict with empirical evidence that sexual differentiation typically involves numerous autosomal genes whose linkage is continuously broken by recombination. Here we develop an evolutionary model of gene regulatory networks (GRNs) to show that disruptive selection favoring complementary mating phenotypes can spontaneously generate a bistable developmental architecture producing two stable sexual phenotypes, together with a master sex-determining locus that biases development toward one or the other. Once such a bistable GRN evolves, the identity of the master regulator becomes flexible, enabling turnover of sex-determining loci without disrupting sexual differentiation. Our results provide a general mechanism for the origin, robustness, and evolutionary lability of sex-determination systems, linking classical gamete-level selection with the emergence of developmental bistability through the evolution of GRNs.