The Drosophila sex determination signal: how do flies count to two?

Seventy years after the discovery that sex in Drosophila melanogaster is determined by the balance between X chromosomes and autosomes, we can finally identify some of the specific genes whose relative dosage is responsible for the male/female decision in somatic cells and study how they act at the molecular level. Discovery of these sex determination genes was delayed because their mutant phenotypes were unanticipated. It now seems appropriate to consider how the concept of the X/A balance may have limited thinking about the fruit fly sex determination signal.