Indirect effects of ploidy suggest X chromosome dose, not the X:A ratio, signals sex in Drosophila

PLoS Biol. 2007 Dec;5(12):e332. doi: 10.1371/journal.pbio.0050332.


In the textbook view, the ratio of X chromosomes to autosome sets, X:A, is the primary signal specifying sexual fate in Drosophila. An alternative idea is that X chromosome number signals sex through the direct actions of several X-encoded signal element (XSE) proteins. In this alternative, the influence of autosome dose on X chromosome counting is largely indirect. Haploids (1X;1A), which possess the male number of X chromosomes but the female X:A of 1.0, and triploid intersexes (XX;AAA), which possess a female dose of two X chromosomes and the ambiguous X:A ratio of 0.67, represent critical tests of these hypotheses. To directly address the effects of ploidy in primary sex determination, we compared the responses of the signal target, the female-specific SxlPe promoter of the switch gene Sex-lethal, in haploid, diploid, and triploid embryos. We found that haploids activate SxlPe because an extra precellular nuclear division elevates total X chromosome numbers and XSE levels beyond those in diploid males. Conversely, triploid embryos cellularize one cycle earlier than diploids, causing premature cessation of SxlPe expression. This prevents XX;AAA embryos from fully engaging the autoregulatory mechanism that maintains subsequent Sxl expression, causing them to develop as sexual mosaics. We conclude that the X:A ratio predicts sexual fate, but does not actively specify it. Instead, the instructive X chromosome signal is more appropriately seen as collective XSE dose in the early embryo. Our findings reiterate that correlations between X:A ratios and cell fates in other organisms need not implicate the value of the ratio as an active signal.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism
  • Female
  • Gene Dosage / genetics*
  • Gene Expression Regulation, Developmental
  • Male
  • Models, Biological
  • Phenotype
  • Ploidies*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Sex Chromosomes / genetics*
  • Sex Determination Processes*
  • Time Factors
  • Transcription, Genetic / genetics


  • Drosophila Proteins
  • RNA-Binding Proteins
  • Sxl protein, Drosophila