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Sex-determination mechanisms and their master regulators are diverse among vertebrates. Components of downstream regulatory pathways can sometimes be co-opted as new upstream triggers. Here, we report a notable finding of cross-pathway recruitment: A gene from the female differentiation cascade was repurposed as a male master sex-determining (MSD) gene. We identify figlaY , a Y-linked truncated duplicate of the female-associated figla , as the MSD gene in Mozambique tilapia. figlaY originated through duplication and translocation in an ancestral cichlid lineage and subsequently introgressed into multiple lineages. Transposable elements facilitated figlaY ’s emergence by mediating duplication, truncation, and regulatory rewiring. Functionally, FIGLAY suppresses the zp2 promoter activated by the FIGLA/E12 heterodimer, acting as a dominant-negative regulator that inhibits ovarian differentiation and promotes testis development. This discovery reveals an unprecedented evolutionary route from female to male sex determination, i.e., a “genetic defection” from an initially female pathway. This previously unknown mechanism expands the vertebrate sex-determination toolkit.
Wang et al. (Wed,) studied this question.