Skip to main content
SpringerLink
Log in

Sex determination in Drosophila melanogaster and Musca domestica converges at the level of the terminal regulator doublesex

  • Original Article
  • Published:
Development Genes and Evolution Aims and scope Submit manuscript

Abstract

Sex-determining cascades are supposed to have evolved in a retrograde manner from bottom to top. Wilkins’ 1995 hypothesis finds support from our comparative studies in Drosophila melanogaster and Musca domestica, two dipteran species that separated some 120 million years ago. The sex-determining cascades in these flies differ at the level of the primary sex-determining signal and their targets, Sxl in Drosophila and F in Musca. Here we present evidence that they converge at the level of the terminal regulator, doublesex (dsx), which conveys the selected sexual fate to the differentiation genes. The dsx homologue in Musca, Md-dsx, encodes male-specific (MdDSXM) and female-specific (MdDSXF) protein variants which correspond in structure to those in Drosophila. Sex-specific regulation of Md-dsx is controlled by the switch gene F via a splicing mechanism that is similar but in some relevant aspects different from that in Drosophila. MdDSXF expression can activate the vitellogenin genes in Drosophila and Musca males, and MdDSXM expression in Drosophila females can cause male-like pigmentation of posterior tergites, suggesting that these Musca dsx variants are conserved not only in structure but also in function. Furthermore, downregulation of Md-dsx activity in Musca by injecting dsRNA into embryos leads to intersexual differentiation of the gonads. These results strongly support a role of Md-dsx as the final regulatory gene in the sex-determining hierarchy of the housefly.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2a–c
Fig. 3
Fig. 4a, b
Fig. 5a, b
Fig. 6a–k
Fig. 7

Similar content being viewed by others

References

  • Agui N, Takahashi M, Wada Y, Izumi S, Tomino S (1985) The relationship between nutrition, vitellogenin, vitellin and ovarian development in the housefly, Musca domestica L. J Insect Physiol 31:715–722

    Article  Google Scholar 

  • An W, Wensink PC (1995a) Integrating sex- and tissue-specific regulation within a single Drosophila enhancer. Genes Dev 9:256–266

    CAS  PubMed  Google Scholar 

  • An W, Wensink PC (1995b) Three protein binding sites form an enhancer that regulates sex- and fat body-specific transcription of Drosophila yolk protein genes. Embo J 14:1221–1230

    CAS  PubMed  Google Scholar 

  • An W, Cho S, Ishii H, Wensink PC (1996) Sex-specific and non-sex-specific oligomerization domains in both of the doublesex transcription factors from Drosophila melanogaster. Mol Cell Biol 16:3106–3111

    CAS  PubMed  Google Scholar 

  • Baker BS, Belote JM (1983) Sex determination and dosage compensation in Drosophila melanogaster. Annu Rev Genet 17:345–393

    Article  CAS  PubMed  Google Scholar 

  • Baker BS, Ridge KA (1980) Sex and the single cell. I. On the action of major loci affecting sex determination in Drosophila melanogaster. Genetics 94:383–423

    CAS  PubMed  Google Scholar 

  • Baker BS, Burtis K, Goralski T, Mattox W, Nagoshi R (1989) Molecular genetic aspects of sex determination in Drosophila melanogaster. Genome 31:638–645

    CAS  PubMed  Google Scholar 

  • Belote JM, Baker B (1982) Sex determination in Drosophila melanogaster: analysis of transformer-2, a sex-transforming locus. Proc Natl Acad Sci USA 79:1568–1572

    CAS  PubMed  Google Scholar 

  • Brand AH, Perrimon N (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118:401–415

    CAS  PubMed  Google Scholar 

  • Burtis KC, Baker BS (1989) Drosophila doublesex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides. Cell 56:997–1010

    CAS  PubMed  Google Scholar 

  • Burtis KC, Coschigano KT, Baker BS, Wensink PC (1991) The doublesex proteins of Drosophila melanogaster bind directly to a sex-specific yolk protein gene enhancer. Embo J 10:2577–2582

    CAS  PubMed  Google Scholar 

  • Chandler DS, Qi J, Mattox W (2003) Direct repression of splicing by transformer-2. Mol Cell Biol 23:5174–5185

    Article  CAS  PubMed  Google Scholar 

  • Cho S, Wensink PC (1997) DNA binding by the male and female doublesex proteins of Drosophila melanogaster. J Biol Chem 272:3185–3189

    Article  CAS  PubMed  Google Scholar 

  • Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159

    CAS  PubMed  Google Scholar 

  • Cline TW (1993) The Drosophila sex determination signal: how do flies count to two? Trends Genet 9:385–390

    Article  CAS  PubMed  Google Scholar 

  • Coates CJ, Johnson KN, Perkins HD, Howells AJ, O’Brochta DA, Atkinson PW (1996) The hermit transposable element of the Australian sheep blowfly, Lucilia cuprina, belongs to the hAT family of transposable elements. Genetica 97:23–31

    CAS  PubMed  Google Scholar 

  • Coschigano KT, Wensink PC (1993) Sex-specific transcriptional regulation by the male and female doublesex proteins of Drosophila. Genes Dev 7:42–54

    CAS  PubMed  Google Scholar 

  • Dubendorfer A, Hediger M (1998) The female-determining gene F of the housefly, Musca domestica, acts maternally to regulate its own zygotic activity. Genetics 150:221–226

    CAS  PubMed  Google Scholar 

  • Dubendorfer A, Hilfiker-Kleiner D, Nothiger R (1992) Sex determination mechanisms in dipteran insects: the case of Musca domestica. Semin Dev Biol 3:349–356

    Google Scholar 

  • Dubendorfer A, Hediger M, Burghardt G, Bopp D (2002) Musca domestica, a window on the evolution of sex-determining mechanisms in insects. Int J Dev Biol 46:75–79

    Google Scholar 

  • Erdman SE, Burtis KC (1993) The Drosophila doublesex proteins share a novel zinc finger related DNA binding domain. Embo J 12:527–535

    CAS  PubMed  Google Scholar 

  • Erdman SE, Chen HJ, Burtis KC (1996) Functional and genetic characterization of the oligomerization and DNA binding properties of the Drosophila doublesex proteins. Genetics 144:1639–1652

    CAS  PubMed  Google Scholar 

  • Guimond N, Bideshi DK, Pinkerton AC, Atkinson PW, O’Brochta DA (2003) Patterns of Hermes transposition in Drosophila melanogaster. Mol Genet Genom 268:779–790

    CAS  Google Scholar 

  • Handler AM, Harrell RA 2nd (1999) Germline transformation of Drosophila melanogaster with the piggyBac transposon vector. Insect Mol Biol 8:449–457

    CAS  Google Scholar 

  • Hediger M, Niessen M, Wimmer EA, Dubendorfer A, Bopp D (2001) Genetic transformation of the housefly Musca domestica with the lepidopteran derived transposon piggyBac. Insect Mol Biol 10:113–119

    CAS  PubMed  Google Scholar 

  • Hedley ML, Maniatis T (1991) Sex-specific splicing and polyadenylation of dsx pre-mRNA requires a sequence that binds specifically to tra-2 protein in vitro. Cell 65:579–586

    CAS  PubMed  Google Scholar 

  • Hertel KJ, Lynch KW, Hsiao EC, Liu EH, Maniatis T (1996) Structural and functional conservation of the Drosophila doublesex splicing enhancer repeat elements. RNA 2:969–981

    CAS  PubMed  Google Scholar 

  • Hildreth PE (1964) doublesex, a recessive gene that transforms both males and females of Drosophila into intersexes. Genetics 51:659–678

    Google Scholar 

  • Hilfiker-Kleiner D, Dubendorfer A, Hilfiker A, Nothiger R (1993) Developmental analysis of two sex-determining genes, M and F, in the housefly, Musca domestica. Genetics 134:1189–1194

    Google Scholar 

  • Horn C, Wimmer EA (2000) A versatile vector set for animal transgenesis. Dev Genes Evol 210:630–637

    CAS  PubMed  Google Scholar 

  • Kopp A, Duncan I, Godt D, Carroll B (2000) Genetic control and evolution of sexually dimorphic characters in Drosophila. Nature 408:553–559

    CAS  PubMed  Google Scholar 

  • Kuhn S, Sievert V, Traut W (2000) The sex-determining gene doublesex in the fly Megaselia scalaris: conserved structure and sex-specific splicing. Genome 43:1011–1020

    Article  CAS  PubMed  Google Scholar 

  • Mattox W, Baker BS (1991) Autoregulation of the splicing of transcripts from the transformer-2 gene of Drosophila. Genes Dev 5:786–796

    CAS  PubMed  Google Scholar 

  • McDonald IC, Evenson P, Nickel CA, Johnson OA (1978) Housefly genetics: isolation of a female determining factor on chromosome 4. Ann Entomol Soc Am 71:692–694

    Google Scholar 

  • McGregor AP, Shaw PJ, Hancock JM, Bopp D, Hediger M, Wratten NS, Dover GA (2001) Rapid restructuring of bicoid-dependent hunchback promoters within and between Dipteran species: implications for molecular coevolution. Evol Dev 3:397–407

    Article  CAS  PubMed  Google Scholar 

  • Meise M, Hilfiker-Kleiner D, Dubendorfer A, Brunner C, Nothiger R, Bopp D (1998) Sex-lethal, the master sex-determining gene in Drosophila, is not sex-specifically regulated in Musca domestica. Development 125:1487–1494

    CAS  PubMed  Google Scholar 

  • Milani R (1967) The genetics of Musca domestica and of other muscoid flies. In: Wright JW, Pal R (eds) Genetics of insect vectors of disease. Elsevier, Amsterdam, pp 315–369

  • Nothiger R, Steinmann-Zwicky M (1985) A single principle for sex determination in insects. Cold Spring Harb Symp Quant Biol 50:615–621

    CAS  PubMed  Google Scholar 

  • Nothiger R, Leuthold M, Andersen N, Gerschwiler P, Gruter A, Keller W, Leist C, Roost M, Schmid H (1987) Genetic and developmental analysis of the sex-determining gene doublesex of Drosophila melanogaster. Genet Res Camb 50:113–123

    Google Scholar 

  • Ohbayashi F, Suzuki MG, Mita K, Okano K, Shimada T (2001) A homologue of the Drosophila doublesex gene is transcribed into sex-specific mRNA isoforms in the silkworm, Bombyx mori. Comp Biochem Physiol B Biochem Mol Biol 128:145–158

    Article  CAS  PubMed  Google Scholar 

  • Pane A, Salvemini M, Delli Bovi P, Polito C, Saccone G (2002) The transformer gene in Ceratitis capitata provides a genetic basis for selecting and remembering the sexual fate. Development 129:3715–3725

    CAS  PubMed  Google Scholar 

  • Pinkerton AC, Michel K, O’Brochta DA, Atkinson PW (2000) Green fluorescent protein as a genetic marker in transgenic Aedes aegypti. Insect Mol Biol 9:1–10

    Article  CAS  PubMed  Google Scholar 

  • Rubini PG, Franco MG, Vanossi Este S (1972) Polymorphisms for heterochromosomes and autosomal sex-determinants in Musca domestica L. Atti del IX Congresso Nazionale Italiano di Entomologia 341–352

  • Ryner LC, Baker BS (1991) Regulation of doublesex pre-mRNA processing occurs by 3′-splice site activation. Genes Dev 5:2071–2085

    CAS  PubMed  Google Scholar 

  • Sarkar A, Coates CJ, Whyard S, Willhoeft U, Atkinson PW, O’Brochta DA (1997) The Hermes element from Musca domestica can transpose in four families of cyclorrhaphan flies. Genetica 99:15–29

    Article  CAS  PubMed  Google Scholar 

  • Schmidt R, Hediger M, Nothiger R, Dubendorfer A (1997) The mutation masculinizer (man) defines a sex-determining gene with maternal and zygotic functions in Musca domestica L. Genetics 145:173–183

    CAS  PubMed  Google Scholar 

  • Schutt C, Nothiger R (2000) Structure, function and evolution of sex-determining systems in Dipteran insects. Development 127:667–677

    CAS  PubMed  Google Scholar 

  • Shearman DC, Frommer M (1998) The Bactrocera tryoni homologue of the Drosophila melanogaster sex-determination gene doublesex. Insect Mol Biol 7:355–366

    Article  CAS  PubMed  Google Scholar 

  • Slee R, Bownes M (1990) Sex determination in Drosophila melanogaster. Q Rev Biol 65:175–204

    CAS  PubMed  Google Scholar 

  • Suzuki MG, Ohbayashi F, Mita K, Shimada T (2001) The mechanism of sex-specific splicing at the doublesex gene is different between Drosophila melanogaster and Bombyx mori. Insect Biochem Mol Biol 31:1201–1211

    Article  CAS  PubMed  Google Scholar 

  • Suzuki MG, Funaguma S, Kanda T, Tamura T, Shimada T (2003) Analysis of the biological functions of a doublesex homologue in Bombyx mori. Dev Genes Evol 213:345–354

    CAS  PubMed  Google Scholar 

  • Tian M, Maniatis T (1993) A splicing enhancer complex controls alternative splicing of doublesex pre-mRNA. Cell 74:105–114

    CAS  PubMed  Google Scholar 

  • Tortiglione C, Bownes M (1997) Conservation and divergence in the control of yolk protein genes in dipteran insects. Dev Genes Evol 207:264–281

    Article  CAS  Google Scholar 

  • Vanossi Este S, Rovati C (1982) Inheritance of the arrhenogenic factor Ag of Musca domestica L. Boll Zool 49:269–278

    Google Scholar 

  • Waterbury JA, Jackson LL, Schedl P (1999) Analysis of the doublesex female protein in Drosophila melanogaster: role on sexual differentiation and behavior and dependence on intersex. Genetics 152:1653–1667

    Google Scholar 

  • White NM, Bownes M (1997) Cloning and characterization of three Musca domestica yolk protein genes. Insect Mol Biol 6:329–341

    Article  CAS  PubMed  Google Scholar 

  • Wilkins AS (1995) Moving up the hierarchy: a hypothesis on the evolution of a genetic sex determination pathway. Bioessays 17:71–77

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are indebted to Drs. Rolf Nöthiger and Markus Niessen for helpful advice and stimulating discussions. Drs. Antonio Pannuti and Giuseppe Saccone are gratefully acknowledged for providing degenerated primers that were used in the initial part of this work. We would also like to thank Dr. Mary Bownes for the anti-Drosophila vitellogenin polyclonal serum and Dr. T. Adams, Fargo, N.D. for his gift of anti-Musca vitellogenin antibodies. We thank Claudia Brunner for technical assistance and Raymond Grunder and Johanna Nägeli for husbandry of the Musca stocks. This work was supported by a grant of the Swiss National Foundation (3100.067993.02/1) and a Novartis fellowship to M.H.

Author information

Authors and Affiliations

  1. Zoological Institute, University Zürich, Winterthurerstrasse 190, 8057, Zurich, Switzerland

    Monika Hediger, Géza Burghardt, Christina Siegenthaler, Nathalie Buser, Denise Hilfiker-Kleiner, Andreas Dübendorfer & Daniel Bopp

Authors
  1. Monika Hediger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Géza Burghardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christina Siegenthaler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nathalie Buser
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Denise Hilfiker-Kleiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andreas Dübendorfer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Daniel Bopp
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel Bopp.

Additional information

Edited by D. Tautz

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hediger, M., Burghardt, G., Siegenthaler, C. et al. Sex determination in Drosophila melanogaster and Musca domestica converges at the level of the terminal regulator doublesex . Dev Genes Evol 214, 29–42 (2004). https://doi.org/10.1007/s00427-003-0372-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00427-003-0372-2

Keywords

Search

Navigation