In most organisms, sex is determined by the ratio of X and Y chromosomes. However, in some organisms, such as Drosophila and C.elegans, sex is determined by the ratio of the number of X chromosomes to the number of sets of autosomes. The Y chromosome in Drosophila is active but does not determine sex. It contains genes responsible for the production of sperms in adult flies.

Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female Drosophila has a ratio of two X chromosomes to two sets of autosomes. Any variation to the ratio of X chromosomes to autosomes leads to different sexual phenotypes, such as a metamale, a metafemale, or an intersex fly.

Interestingly, each cell in Drosophila can make an independent choice regarding sex depending on the X: A ratio. This may result in gynandromorphs - an organism with some male body parts and some female. For example, if an embryonic nucleus with XX chromosome loses one of the X chromosomes, all its progeny cells will have XO chromosomes. The cells with XX chromosomes will display female traits in such an organism, while the cells with XO chromosomes will display male characteristics.

So how does the ratio of X: A determine sex in Drosophila? The X chromosome encodes ‘numerator proteins,’ such as Sisterless, and the autosomes encode ‘denominator proteins,’ such as Deadpan. These are sex determinant proteins that display antagonistic activity inside the cell and regulate the expression of the feminizing switch gene Sex-lethal or Sxl. The differential RNA processing of the Sxl gene determines the male flies from the female flies.