EVOLUTIONARY CONSERVATION OF REGULATORY STRATEGIES FOR THE SEX DETERMINATION FACTOR TRANSFORMER-2

Sex determination in Drosophila melanogaster is regulated by a cascade of splicing factors which direct the sex-specific expression of gene products needed for male and female differentiation, The splicing fact or TRA-2 affects sex-specific splicing of multiple pre-mRNAs involved in sexual differentiation. The tra-2 gene itself expresses a complex s et of mRNAs generated through alternative processing that collectively encode three distinct protein isoforms, The expression of these isofo rms differs in the soma and germ line, In the male germ line the ratio of two isoforms present is governed by autoregulation of splicing, Ho w ever, the functional significance of multiple TRA-2 isoforms has rem ained uncertain, Here we have examined whether the structure, function , and regulation of tra-2 are conserved in Drosophila virilis, a speci es diverged from D. melanogaster by over 60 million gears. We find tha t the D. virilis homolog of tra-2 produces alternatively spliced RNAs encoding a set of protein isoforms analogous to those found in D, mela nogaster. When introduced into the genome of D, melanogaster, this hom olog can functionally replace the endogenous tra-2 gene for both norma l female sexual differentiation and spermatogenesis. Examination of al ternative mRNAs produced in D, virilis testes suggests that germ line- specific autoregulation of tra-2 function is accomplished by a strateg y similar to that used in D. melanogaster, The similarity in structure and function of the tra-2 genes in these divergent Drosophila species supports the idea that sexual differentiation in D. melanogaster and D. virilis is accomplished under the control of similar regulatory pat hways.