Nature has evolved an astonishing variety of genetic and epigenetic sex-det
ermining systems which all achieve the same result, the generation of two s
exes. Genetic and molecular analyses, mainly performed during the last 20 y
ears, have gradually revealed the mechanisms that govern sexual differentia
tion in a few model organisms. In this review, we will introduce the sex-de
termining system of Drosophila and compare the fruitfly to the housefly Mus
ca domestica and other Dipteran insects. Despite the ostensible variety, al
l these insects use the same basic strategy: a primary genetic signal that
is different in males and females, a key gene that responds to the primary
signal, and a double-switch gene that eventually selects between two altern
ative sexual programmes. These parallels, however, do not extend to the mol
ecular level. Except for the double-switch gene doublesex at the end of the
cascade, no functional homologies were found between more distantly relate
d insects, In particular, Sex-lethal, the key gene that controls sexual dif
ferentiation in Drosophila, does not have a sex-determining function in any
other genus studied so far. These results show that sex-determining cascad
es, in comparison to other regulatory pathways, evolve much more rapidly.