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

Abstract

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.

Genomic Imprinting and Maternal Effect Genes in Haplodiploid Sex Determination

“…Moreover, prevention of maternal Nvtra mRNA did not only lead to disrupted splicing of zygotic Nvdsx pre-mRNA, but also to a disruption of Nvtra pre-mRNA splicing itself. This indicates that Nvtra female-specific splicing also establishes an autoregulatory memory loop, as has been found in several other insect species [Pane et al, 2002;Ruiz et al, 2007;Concha and Scott, 2009;Gempe et al, 2009;Salvemini et al, 2009;Hediger et al, 2010;Saccone et al, 2011]. As blocking maternal provision of female-specific Nvtra mRNA led to a complete sex-reversal of diploid offspring, surprisingly, the mother provides feminizing in addition to masculinizing information to the zygote.…”

“…The presence of such a feminizing loop has been demonstrated for both dipteran and hymenopteran species [Pane et al, 2002;Concha and Scott, 2009;Gempe et al, 2009;Salvemini et al, 2009;Hediger et al, 2010;Saccone et al, 2011]. Only in D. melanogaster this function has been taken over by Sxl [Siera and Cline, 2008].…”

Sex Determination in Insects: Variations on a Common Theme

“…Hence, the ancestral module may have consisted of tra and possibly both effectors dsx and fru to faithfully implement the sexual programs imposed by the instructive signals. Tra also plays a crucial part in maintaining the selected fate epigenetically [Saccone et al, 2011]. It acts as a cellular memory for female development, a key feature first discovered in Ceratitis .…”

Male only progeny in Anastrepha suspensa by RNAi-induced sex reversion of chromosomal females

“…In addition it has been found that Cctra and Cctra-2 play a novel epigenetic function in the medfly, being both required to maintain the female sexual fate established during embryogenesis (Saccone et al, 2011). Analogous epigenetic functions in Drosophila are controlled by the master ON/ OFF gene Sxl, and by its auxiliary splicing factor, fl(2)d (Granadino et al, 1990).…”