Fig. 1

Sex determination in insect species. Orders, suborders and families of species with identified sex determining genes reported in figure are indicated. In the model system Drosophila melanogaster, the presence of two X chromosomes in the female embryo activates the Sex-lethal gene (Sxl) which, acting as a gene-specific splicing regulator, promotes the female-specific splicing of its own pre-mRNA and of the pre-mRNA of the downstream gene transformer (tra) in the regulative cascade. Tra and the non-sex-specific auxiliary factor transformer-2 (tra-2) encode for splicing factors (TRA and TRA-2 proteins) able to control the splicing of at least two downstream target genes, responsible of sexual differentiation and courtship behaviour: doublesex (dsx) and fruitless (fru), respectively. Both genes encode for sex-specific transcription factors that potentially binds to multiple genome loci, leading to sex-specific gene expression and subsequent sexual differentiation. In male embryo, the absence of the functional SXL protein leads to the male-specific splicing of tra, dsx and fru pre-mRNAs resulting in the activation of the male development program. In Hymenoptera, Coleoptera, and Diptera (Brachycera), different primary signals set the activity state of the tra homolog able to autoregulate its own splicing in the female sex and to determine female development. In mosquitoes (Diptera, Nematocera) dsx and fru genes exhibit, as for Brachycera species, a conserved alternative splicing regulation, producing sex-specific protein isoforms. Recently, genomic/transcriptomic studies of sex determination led to the discovery of novel primary signals including the Y-linked genes Yob and Guy-1 in the malaria vectors Anopheles gambiae and An. stephensi, respectively, and the putative splicing factors Nix in the dengue vector Aedes aegypti. These primary signals are supposed to act upstream of dsx and fru genes in the sex determination cascade. However, their mechanism of action, direct or indirect, and the possible presence of an intermediate upstream regulator of dsx and fru splicing, is still an open question