Genes involved in sex differentiation, epigenetic reprogramming, and cell fate regulate sex change in a wrasse

Summary statement Socially induced sex change is orchestrated by a novel combination of genes and epigenetic factors that govern sex differentiation and cell fate. Approximately 500 fish species can change sex in adulthood. The molecular basis for this astonishing transformation remains broadly unknown. Genetic regulation of embryonic sex differentiation is well established in vertebrates but also appears influential in sequential hermaphrodites. Recent work indicates that epigenetic effects and genes regulating cell fate are also important drivers of sex change. Here we use the spotty wrasse to investigate gonadal sex change at a molecular level. While the expression of some sex differentiation genes ( dmrt1, foxl2a, ctnnb1 ) in spotty wrasse follow established sex-biased patterns, others ( sox9a, znrf3, rspo1 ) oppose typical vertebrate-models. We propose that gene neofunctionalisation due to teleost whole-genome duplication may explain these counter-intuitive expression profiles. Significant epigenetic reprogramming within the transitional spotty wrasse gonad is implied through the dynamic expression of methyltransferases and the chromatin-modifying Jumonji family genes, jarid2b and kdm6bb . Furthermore, our results show that fancl and pou5f3 , two genes associated with either DNA repair pathways or stem cell pluripotency, are downregulated as sex change advances. This highlights genetic factors that may underlie a functional change of cell fate trajectory. Collectively, this work demonstrates the diversity of genetic pathways that are dynamically activated in a phased, sex-specific manner to co-ordinate vertebrate sex change.