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

Dev Genes Evol. 2004 Jan;214(1):29-42. doi: 10.1007/s00427-003-0372-2. Epub 2003 Dec 13.


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 (MdDSX(M)) and female-specific (MdDSX(F)) 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. MdDSX(F) expression can activate the vitellogenin genes in Drosophila and Musca males, and MdDSX(M) 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Biological Evolution
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Genetic Variation / genetics
  • Houseflies / embryology*
  • Houseflies / genetics*
  • Houseflies / metabolism
  • Insect Proteins / chemistry
  • Insect Proteins / genetics*
  • Insect Proteins / metabolism*
  • Male
  • Molecular Sequence Data
  • RNA Interference
  • RNA Splice Sites / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Regulatory Sequences, Ribonucleic Acid / genetics
  • Sequence Homology
  • Sex Characteristics
  • Sex Determination Processes*
  • Sex Differentiation / genetics
  • Vitellogenins / genetics


  • DNA-Binding Proteins
  • DSX protein, Drosophila
  • Drosophila Proteins
  • Insect Proteins
  • RNA Splice Sites
  • RNA, Messenger
  • Regulatory Sequences, Ribonucleic Acid
  • Vitellogenins