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Sex determination in reptiles is a complex affair, because incubation temperature and genes interact in many species to regulate sexual development and decide sexual fate, male or female (1–4). A central question that has remained unanswered is, what molecular mechanism allows temperature to so profoundly influence the developmental pathways that determine sex? The means to identify a master sex-determining gene in species with genetic sex determination is well established—identify genes on the sex chromosomes, demonstrate which of these are differentially expressed in male and female embryos early in development, and manipulate their expression to demonstrate reversal of sex (5–7). Not so with identifying the mechanisms of temperature-dependent sex determination (TSD). Temperature could exert its effect on any of the many autosomal genes involved in sexual differentiation, even those …