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Gene Review

dsx  -  doublesex

Drosophila melanogaster

Synonyms: CG11094, DSX, Dmdsx, Dmel\CG11094, Dsx, ...
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Disease relevance of dsx


Psychiatry related information on dsx

  • The position of such QTL (approximately 84A-88B) with effects on courtship and copulation aspects of mating includes the candidate sex determination gene doublesex (84E5-6) and Voila (86E1-2), a gene that affects male courtship in D. melanogaster [3].

High impact information on dsx

  • Thus, we show that fru and dsx together act as a 'switch' system regulating behavior in the context of other developmental genes, such as retn [4].
  • Current models describe male-specific fruitless (fruM) as a genetic 'switch' regulating sexual behavior in Drosophila melanogaster, and they postulate that female (F) and male (M) doublesex (dsx) products control body sexual morphology [4].
  • Male-specific deployment of FGF signaling is controlled by the sex determination regulatory gene doublesex [5].
  • Characterization of the proteins associated with affinity-purified complex formed on dsx pre-mRNA reveals the presence of Tra, Tra2, SR proteins, and additional unidentified components [6].
  • A splicing enhancer complex controls alternative splicing of doublesex pre-mRNA [6].

Biological context of dsx

  • Sex-specific splicing and polyadenylation of dsx pre-mRNA requires a sequence that binds specifically to tra-2 protein in vitro [1].
  • Furthermore, analyses of mutant constructs of dsx showed that a portion of the female-specific exon sequence was required for regulation of dsx pre-messenger RNA splicing [7].
  • Thus positive control of dsx pre-mRNA splicing requires the Tra- and Tra2-dependent assembly of a multiprotein complex on at least two distinct enhancer elements [8].
  • Use of the more downstream male-specific terminal exons does not require the activities of these genes and is thus considered the default dsx-processing pattern [9].
  • When expressed in flies, one hTRA-2 alpha isoform partially replaces the function of Drosophila TRA-2, affecting both female sexual differentiation and alternative splicing of dsx pre-mRNA [10].

Anatomical context of dsx

  • Taken together, these findings suggest that the sex-determination protein Tra has at least three different targets, dsx, fru and dsf, each of which represents the first gene in a branch of the sex-determination hierarchy functioning in a mutually-exclusive set of neuronal cells in the Drosophila central nervous system [11].
  • However, feminization of XY germ cells by Tra(F) can be blocked by the male form of the Dsx protein (Dsx(M)) [2].
  • Flies homozygous for dsx, both X/X and X/Y, have hemolymph vitellogenins, although the amount is consistently smaller in the latter [12].
  • Furthermore, downregulation of Md-dsx activity in Musca by injecting dsRNA into embryos leads to intersexual differentiation of the gonads [13].
  • The Caenorhabditis elegans hermaphrodite sequentially produces sperm and oocytes from a single pool of precursors [14].

Associations of dsx with chemical compounds

  • Using a tissue culture transfection assay, we demonstrate that the Gly residues within the Gly-rich domain, the ribonucleoprotein motifs within the RNA recognition motif RNA binding domain, and the SR domain are required for regulation of dsx splicing by RBP1 in vivo [15].
  • We have further shown that of 10 null dsx alleles, six encode proteins deficient in DNA binding activity, and that three of these alleles are the result of mutations that alter cysteine and histidine residues in the metal binding domain [16].
  • Transcription of the genes is regulated by the genes tra, tra-2 and dsx and also by the insect hormones, juvenile hormone and 20-hydroxyecdysone [17].
  • Thus, the hemolymph vitellogenins serve as an easily detectable sexually dimorphic biochemical marker.--We have examined hemolymph vitellogenins by SDS polyacrylamide gel electrophoresis in flies carrying various sex-transformation mutants (dsx, tra, tra-2 and tra-2OTF) singly and in all possible combinations [12].
  • In the present study, we show that SRm160/300 is required for a purine-rich ESE to promote the splicing of a pre-mRNA derived from the Drosophila doublesex gene [18].

Regulatory relationships of dsx

  • These and other results support the model that the tra-2+ and tra+ loci act to control the expression of the bifunctional doublesex (dsx) locus [19].
  • Most importantly, a signal from the somatic sex-determination pathway that is dependent on the male-specific isoform of the doublesex protein (DSX(M)) regulates PTB, providing evidence for the necessity of soma-germline communication in the differentiation of the male germline [20].
  • In somatic cells, the product of tra regulates the expression of the gene double sex (dsx) which can form a male-specific or a female-specific product [21].

Other interactions of dsx

  • These studies reveal that female-specific processing of dsx pre-mRNA is controlled by tra and tra-2 through the positive regulation of female-specific alternative 3'-terminal exon use [9].
  • Examination of pre-mRNAs regulated similarly to dsx shows that the requirement for Doa is substrate specific [22].
  • Fragments of the Sxl and dsx orthologous were isolated with RT-PCR [23].
  • To test this, we cloned insect and vertebrate homologs of the Drosophila gene intersex (ix), which functions together with dsx at the bottom of the hierarchy in females [24].
  • It does so by recognizing RBP1 RNA target sequences in the dsx pre-mRNA [15].

Analytical, diagnostic and therapeutic context of dsx

  • Northern blot analysis showed that the transcript levels from the dsx gene are not affected by nutrition, indicating that the response is not mediated via the dsx gene [25].
  • Using gel mobility shift experiments with sequentially deleted polypeptides, site-directed mutagenesis and spectrophotometric assays, we have shown that the two doublesex proteins share a common and novel zinc finger-related DNA binding domain distinct from any reported class of zinc binding proteins [16].
  • Expression, crystallization and preliminary X-ray characterization of the Drosophila transcription factor Doublesex [26].


  1. Sex-specific splicing and polyadenylation of dsx pre-mRNA requires a sequence that binds specifically to tra-2 protein in vitro. Hedley, M.L., Maniatis, T. Cell (1991) [Pubmed]
  2. Sex determination in the Drosophila germline is dictated by the sexual identity of the surrounding soma. Waterbury, J.A., Horabin, J.I., Bopp, D., Schedl, P. Genetics (2000) [Pubmed]
  3. The genetics of mating recognition between Drosophila simulans and D. sechellia. Civetta, A., Cantor, E.J. Genet. Res. (2003) [Pubmed]
  4. A double-switch system regulates male courtship behavior in male and female Drosophila melanogaster. Shirangi, T.R., Taylor, B.J., McKeown, M. Nat. Genet. (2006) [Pubmed]
  5. Sex-specific deployment of FGF signaling in Drosophila recruits mesodermal cells into the male genital imaginal disc. Ahmad, S.M., Baker, B.S. Cell (2002) [Pubmed]
  6. A splicing enhancer complex controls alternative splicing of doublesex pre-mRNA. Tian, M., Maniatis, T. Cell (1993) [Pubmed]
  7. Control of doublesex alternative splicing by transformer and transformer-2 in Drosophila. Hoshijima, K., Inoue, K., Higuchi, I., Sakamoto, H., Shimura, Y. Science (1991) [Pubmed]
  8. Synergistic interactions between two distinct elements of a regulated splicing enhancer. Lynch, K.W., Maniatis, T. Genes Dev. (1995) [Pubmed]
  9. Regulation of doublesex pre-mRNA processing occurs by 3'-splice site activation. Ryner, L.C., Baker, B.S. Genes Dev. (1991) [Pubmed]
  10. A human homologue of the Drosophila sex determination factor transformer-2 has conserved splicing regulatory functions. Dauwalder, B., Amaya-Manzanares, F., Mattox, W. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  11. From behavior to development: genes for sexual behavior define the neuronal sexual switch in Drosophila. Yamamoto, D., Fujitani, K., Usui, K., Ito, H., Nakano, Y. Mech. Dev. (1998) [Pubmed]
  12. Interactions between sex-transformation mutants of Drosophila melanogaster. I. Hemolymph vitellogenins and gonad morphology. Ota, T., Fukunaga, A., Kawabe, M., Oishi, K. Genetics (1981) [Pubmed]
  13. Sex determination in Drosophila melanogaster and Musca domestica converges at the level of the terminal regulator doublesex. Hediger, M., Burghardt, G., Siegenthaler, C., Buser, N., Hilfiker-Kleiner, D., Dübendorfer, A., Bopp, D. Dev. Genes Evol. (2004) [Pubmed]
  14. RNA and sex determination in Caenorhabditis elegans. Post-transcriptional regulation of the sex-determining tra-2 and fem-3 mRNAs in the Caenorhabditis elegans hermaphrodite. Puoti, A., Pugnale, P., Belfiore, M., Schläppi, A.C., Saudan, Z. EMBO Rep. (2001) [Pubmed]
  15. In vivo analysis of the functional domains of the Drosophila splicing regulator RBP1. Heinrichs, V., Baker, B.S. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  16. The Drosophila doublesex proteins share a novel zinc finger related DNA binding domain. Erdman, S.E., Burtis, K.C. EMBO J. (1993) [Pubmed]
  17. Dietary components modulate yolk protein gene transcription in Drosophila melanogaster. Bownes, M., Scott, A., Shirras, A. Development (1988) [Pubmed]
  18. The SRm160/300 splicing coactivator is required for exon-enhancer function. Eldridge, A.G., Li, Y., Sharp, P.A., Blencowe, B.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  19. Sex determination in Drosophila melanogaster: analysis of transformer-2, a sex-transforming locus. Belote, J.M., Baker, B.S. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  20. Drosophila polypyrimidine-tract binding protein (PTB) functions specifically in the male germline. Robida, M.D., Singh, R. EMBO J. (2003) [Pubmed]
  21. Sex determination of the Drosophila germ line: tra and dsx control somatic inductive signals. Steinmann-Zwicky, M. Development (1994) [Pubmed]
  22. Protein phosphorylation plays an essential role in the regulation of alternative splicing and sex determination in Drosophila. Du, C., McGuffin, M.E., Dauwalder, B., Rabinow, L., Mattox, W. Mol. Cell (1998) [Pubmed]
  23. Isolation and characterization of the Bactrocera oleae genes orthologous to the sex determining Sex-lethal and doublesex genes of Drosophila melanogaster. Lagos, D., Ruiz, M.F., Sánchez, L., Komitopoulou, K. Gene (2005) [Pubmed]
  24. Functional conservation and divergence of intersex, a gene required for female differentiation in Drosophila melanogaster. Siegal, M.L., Baker, B.S. Dev. Genes Evol. (2005) [Pubmed]
  25. Nutritional response in a Drosophila yolk protein gene promoter. Søndergaard, L., Mauchline, D., Egetoft, P., White, N., Wulff, P., Bownes, M. Mol. Gen. Genet. (1995) [Pubmed]
  26. Expression, crystallization and preliminary X-ray characterization of the Drosophila transcription factor Doublesex. Bayrer, J., Wan, Z., Li, B., Weiss, M.A. Acta Crystallogr. D Biol. Crystallogr. (2004) [Pubmed]
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