Epigenetic modification and inheritance in sexual reversal of tongue-sole fish

Two major sex determining mechanisms are known to occur: Genetic (GSD) and environmental (ESD) sex determination. The genetic mechanisms behind GSD are now relatively well documented in a range of model species, but the molecular biology of ESD remains poorly understood. Using the half-smooth tongue sole fish (Cynoglossus semilaevis) , which have both ZW chromosomal GSD and temperature-dependent sex determination (TSD or ESD), we investigated the role of DNA methylation in the realization of ESD and in the interaction between GSD and ESD. We show that high temperature (28ºC) can induce sex reversal of juvenile genotypic females into phenotypic pseudo-males by epigenetically regulating genes involving the sex determination. During this process, dosage compensation occurs in a Z chromosome region in the testes of pseudo-males, enabling them to overcome insufficient gene expression relative to normal ZZ males. We further show that female-specific W chromosome genes are inhibited in ZW pseudo-males, quite possibly because their expression would be detrimental for realizing a normal male phenotype. Finally, we show that this epigenetic modification can be passed down to the ZW offspring of pseudo males without high temperature induction, so that most of these genetically female offspring become phenotypic males. We conclude that epigenetic regulation plays an important role during sexual reversal in tongue-sole fish, and that sex reversal can be inherited across generations by epigenetic mechanisms.