Sex Determination in Drosophila Melanogaster

What makes a fruit fly become a male or female?

The process of sex determination in the fruit fly, Drosophila melanogaster, is achieved in a remarkable way by a regulated series of alternative splicing events or more precisely, a cascade of RNA splicing reactions.

Physical appearance of Drosophila melanogaster

Fruit flies have red eyes, are yellow-brown in colour, and show black rings across their abdomen. Male and female individuals look different: females (above right) are about 2.5 millimetres (0.1 inches) long; males (above left) are smaller and the back of their bodies are darker. Additionally, males have a black patch at the abdomen and they show a cluster of spiky hairs (claspers) surrounding the anus and genitals. This is used to attach to the female during mating.

Initiating the regulation pathway

The primary signal determining whether the fly develops as a male or female is the number of X chromosomes relative to the number of autosomes (non-sex chromosomes) in a cell (the X:A ratio). Individuals carrying one X chromosome and two sets of autosomes are male (X:A=0.5), whereas individuals with an equal number of X and autosomal chromosomes are female (X:A=1).

In Drosophila the Y chromosome does not play a role in sex determination like in humans!

The first response to the ratio of X:A is the activation or inactivation of the Sex-lethal gene (SXl). In the case of a female fly the gene is activated and the SXL protein is produced; in male flies the SXl gene is inactive and no SXL protein is produced.

SXL (Sex-lethal) - The major player: A protein with three responsibilities

In the female fly, the SXL protein determines all aspects of terminal differentiation. It activates a pathway of reactions that leads to female-specific gene expression. Each subsequent gene controls only one “following” gene in the cascade.

The SXL protein determines the splicing pattern of the tra (transformer) transcript in such a way as to produce an active TRA protein. The TRA protein itself is an RNA-binding protein that ensures that the following dsx (doublesex) RNA is spliced in a female-specific way.

DSX – The doublesex protein

TRA can form dimers with the TRA2 protein and causes splicing of DSX to a short form in females (DSXF). In males, where no SXL or TRA protein is made, DSX is spliced into a longer form (DSXM). DSXF triggers female gene expression and DSXM (in the male) blocks female gene expression.

The highly regulated alternative splicing pathway therefore determines whether ‘male’ or ‘female’ genes are expressed to determine the sex of the fly.