The Questions of Developmental Biology

Doublesex: The switch gene of sex determination
To do this, the Sxl protein blocks the
binding of splicing factor U2AF to the nonspecific
splice site by specifically binding to the
polypyrimidine tract adjacent to it (Figure 17.19;
Handa et al. 1999). This causes U2AF to bind to
the lower-affinity (female-specific) 3´ splice site
and generate a female-specific mRNA (Valcárcel
et al. 1993). The female-specific tra product acts
in concert with the product of the transformer-2
(tra2) gene to help generate the female phenotype.
The doublesex (dsx) gene is active in both males and females, but its primary transcript is
processed in a sex-specific manner (Baker et al. 1987). This alternative RNA processing appears
to be the result of the action of the transformer gene products on the dsx gene (see Figure 5.31).
If the Tra2 and female-specific Tra proteins are both present, the dsx transcript is processed in a
female-specific manner (Ryner and Baker 1991). The female splicing pattern produces a femalespecific
protein that activates female-specific genes (such as those of the yolk proteins) and
inhibits male development. As discussed in Chapter 5, if functional Tra is not produced, a malespecific
transcript of dsx is made. This transcript encodes an active protein that inhibits female
traits and promotes male traits.
The functions of the Doublesex proteins can be seen in the formation of the Drosophila
genitalia. Male and female genitalia in Drosophila are derived from separate cell populations.
In male (XY) flies, the female primordium is repressed, and the male primordium differentiates
into the adult genital structures. In female (XX) flies, the male primordium is repressed, and the
female primordium differentiates. If the dsx gene is absent (and thus neither transcript is made),
both the male and the female primordia develop, and intersexual genitalia are produced.
Similarly, in the fat body of Drosophila, activation of the genes for egg yolk production is
stimulated by the female Dsx protein and is inhibited by the male Dsx protein (Schüpbach et al.
1978; Coschigano and Wensink 1993; Jursnich and Burtis 1993).
According to this model (Baker 1989), the result of the sex determination cascade comes
down to what type of mRNA is going to be processed from the dsx transcript. If the X:A ratio is
1, then Sxl makes a female-specific splicing factor that causes the tra gene transcript to be spliced
in a female-specific manner. This female-specific protein interacts with the Tra2 splicing factor to
cause the doublesex pre-mRNA to be spliced in a female-specific manner. If the doublesex
transcript is not acted on in this way, it will be processed in a "default" manner to make the malespecific
message.
Environmental Sex Determination
Temperature-dependent sex determination in reptiles
While the sex of most snakes and most lizards is determined by sex chromosomes at the
time of fertilization, the sex of most turtles and all species of crocodilians is determined by the
environment after fertilization. In these reptiles, the temperature of the eggs during a certain
period of development is the deciding factor in determining sex, and small changes in
temperature can cause dramatic changes in the sex ratio (Bull 1980).