Drosophila Sex Determination
Χɴ= Drosophila Sex Determination =
In Drosophila, sex is determined by the X:autosome ratio and is independent of the Y chromosome.
XX:AA = female
X:AA = male
XX:AAA = intersex; these individuals are sexual mosaics; individual cells are either fully female or fully male
Pathway Deduction from Genetics
Phenotype examination of double mutants establish the sex determination pathway:
dsx is epistatic to tra, tra-2, Sxl
dsx and ix are indistinguishable in females; ix is placed downstream because it only effects females.
tra and tra-2 are epistatic to Sxl but not distinguishable from each other
Sex Specific Lethality
Sxl and upstream genes effect dosage compensation, thus they result in sex-specific lethality instead of transformations.
X:autosome ratio is assessed early and then no longer needed. Once Sxl is activated, it is autoregulated in females, da, sis-a, and sis-b are only needed for initial signal first.
Molecular Analysis of Drosophila Sex Determination
dsx can be alternatively spliced to give 2 RNAs differing at their 3' end (they use different splice acceptor sites.
Mutations in the splice acceptor of the female specific exon lead to default use of male-specific exons. Tra and tra-2 thus promote the female specific splice rather than inhibit the male specific splice.
tra can be alternatively spliced to give sex-nonspecific RNA and female specific RNA
Non-specific RNA includes a stop codon and produces no active product. Its splicing is regulated by Sxl and unaffected by tra-2. Sxl blocks use of the non-specific acceptor site.
Sxl has no effect on tra-2 transcripts. Sxl exerts control of somatic sex solely by effects on tra.
Tra-2 is only functionally active in the presence of tra gene product. Active product of tra-2 has homology to RNA-binding domains of splicing factors.
Like tra-2 the active product of Sxl has homology to RNA-binding domains of splicing factors. Early Sxl expression is from a different promoter which is sensitive to X:A ration. At later times, Sxl product made from this early promoter can prevent splicing to the male exon and allow the production of female-specific RNA.
sis-a and sis-b
Sis-a and sis-b function by counting X chromosomes. da and sis-b encode helix-loop-helix proteins which function as heterodimers. Da is supplied maternally in excess. Dosage of sis-b determines the amount of helix-loop-helix heterodimer that can bind to Sxl and activate it.
Hairy is another helix-loop-helix protein which, when bound to sis-b makes an inactive dimer. Sxl is no longer activated in the presence of hairy protein.