The transformer gene of Ceratitis capitata: a paradigm for a conserved epigenetic master regulator of sex determination in insects.

The transformer gene in Ceratitis capitata (Cctra(ep)) is the founding member of a family of related SR genes that appear to act as the master epigenetic switch in sex determination in insects. A functional protein seems to be produced only in individuals with a female XX karyotype where it is required to maintain the productive mode of expression through a positive feedback loop and to direct female development by instructing the downstream target genes accordingly. When zygotic activation of this loop is prevented, male development follows. Recently, tra(ep) orthologues were isolated in more distantly related dipteran species including Musca domestica, Glossina morsitans and Lucilia cuprina and in the Hymenopterans Apis mellifera and Nasonia vitripennis. All of these tra(ep) orthologues seem to act as binary switches that govern all aspects of sexual development. Transient silencing leads to complete masculinization of individuals with a female karyotype. Reciprocally, in some systems it has been shown that transient expression of the functional TRA product is sufficient to transactivate the endogenous gene and implement female development in individuals with a male karyotype. Hence, a mechanism based on tra(ep) epigenetic autoregulation seems to represent a common and presumably ancestral single principle of sex determination in Insecta. The results of these studies will not only be important for understanding divergent evolution of basic developmental processes but also for designing new strategies to improve genetic sexing in different insect species of economical or medical importance.