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 sex index ratio =1, normal demale =o.5, male >1, super female or meta female <0.5, super male or meta male between 0.5 to 1, intersex these are points to remember

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.

dsx
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
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.

Sxl
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
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.

quiz
{dsx can be alternatively spliced to give 2 RNAs differing at their ______ end. + 3' - 5' - middle - start
 * type="[]"}
 * Correct! The RNAs differ at their 3' end.
 * Incorrect. Review the information provided.
 * Incorrect. The RNAs differ at their 3' end.
 * Incorrect. Review the information provided.

{Mutations in the splice acceptor of the female specific exon lead to default use of ______ exons. + male-specific - female-specific - non-specific - both male and female
 * type="[]"}
 * Correct! Mutations lead to the default use of male-specific exons.
 * Incorrect. Review the information provided.
 * Incorrect. The mutations lead to male-specific exons.
 * Incorrect. Review the information provided.

{tra can be alternatively spliced to give ______ RNA and female specific RNA. + sex-nonspecific - male-specific - both male and female - none of the above
 * type="[]"}
 * Correct! tra gives sex-nonspecific RNA and female specific RNA.
 * Incorrect. Review the information provided.
 * Incorrect. tra gives sex-nonspecific and female specific RNA.
 * Incorrect. Review the information provided.

{Non-specific RNA includes a stop codon and produces no ______. + active product - inactive product - RNA product - DNA product
 * type="[]"}
 * Correct! Non-specific RNA produces no active product.
 * Incorrect. Review the information provided.
 * Incorrect. Non-specific RNA produces no active product.
 * Incorrect. Review the information provided.

{Sxl exerts control of somatic sex solely by effects on ______. + tra - tra-2 - dsx - none of the above
 * type="[]"}
 * Correct! Sxl exerts control by effects on tra.
 * Incorrect. Review the information provided.
 * Incorrect. Sxl affects tra.
 * Incorrect. Review the information provided.

{Tra-2 is only functionally active in the presence of ______ gene product. + tra - dsx - Sxl - none of the above
 * type="[]"}
 * Correct! Tra-2 is active in the presence of tra gene product.
 * Incorrect. Review the information provided.
 * Incorrect. Tra-2 is active in the presence of tra.
 * Incorrect. Review the information provided.

{Sis-a and sis-b function by ______. + counting X chromosomes - counting Y chromosomes - splicing RNA - none of the above
 * type="[]"}
 * Correct! Sis-a and sis-b function by counting X chromosomes.
 * Incorrect. Review the information provided.
 * Incorrect. Sis-a and sis-b count X chromosomes.
 * Incorrect. Review the information provided.

{Hairy is another helix-loop-helix protein which, when bound to sis-b makes an ______. + inactive dimer - active dimer - RNA product - none of the above
 * type="[]"}
 * Correct! Hairy makes an inactive dimer when bound to sis-b.
 * Incorrect. Review the information provided.
 * Incorrect. Hairy makes an inactive dimer with sis-b.
 * Incorrect. Review the information provided.