Download Sex Determination in Drosophila

Sex Determination in Drosophila
What is the Role of Sex
Chromosomes in Drosophila?
• Humans: XX = female; XY = male
• Flies:
XX = female; XY = male
• Humans: XXY = male; XO = female
• Flies:
XXY = female; XO = male
• The number of X chromosomes is important?
– Absolute or relative to the number of autosome sets
(two)?
X:Autosome Ratio is Critical
• XX = female;
XY = male
• XXY = female;
XO = male
• RULE:
– 2X : 2A --> female
– 1X : 2A --> male
How to Measure the X:A Ratio?
• Numerator proteins are encoded by X
– Sis-a, sis-b, sis-c, runt, dpn
• Denominator proteins encoded by
autosomes
– Da, her, emc, gro
• Numerator proteins are transcription factors
• Denominator proteins block numerators,
probably by forming inactive dimers
Several Mutations Affect Drosophila
Sex Determination
XX
•
•
•
•
XY
sex-lethal (Sxl)
male (dead) male
transformer (tra)
male
male
transformer 2 (tra2) male
male
doublesex (dsx) intersex
intersex
Sxl
• Master regulatory protein that controls all
aspects of sexual development
• X:A ratio controls Sxl transcription
– Brief window: early promoter
What Does Sxl Do?
• Sxl = RNA-binding protein
– Binds pre-mRNAs: sxl, tra, dsx
– Causes “female-specific” mode of splicing
Sex-specific RNA Splicing Cascade
Sex-specific RNA Splicing Cascade
Sex-specific RNA Splicing Cascade
Doublesex is Needed for Both Sexes
XX
•
•
•
•
XY
Sex-lethal (Sxl) male(dead)
male
transformer (tra)
male
male
transformer 2 (tra2) male
male
doublesex (dsx) intersex
intersex
Regulation of Somatic Sex in
Drosophila
• Female
Male
Summary Drosophila
• Calculation of X/A
• Importance of splicing controls
• Cascade of interactions
C. elegans
Worm Choice
• Somatic sex
differentiation
Hermaphrodite
– hermaphrodite or
male body?
Male
Initial Trigger is X:A ratio
Chromosomes Autosomes X:A ratio Sex
XX
2
2/2 (1)
herm
X
2
1/2 (0.5) male
XX
XXX
3
4
2/3 (0.67) male
3/4 (0.75) herm
Reading of X:A Ratio is Similar to
Fly
• Numerator proteins = X-linked genes
– fox-1 and sex-1 and others
– Prevent expression of master regulatory gene:
xol-1
• Denominator proteins (autosome-linked) still
unknown
What Are Key Downstream Genes?
XX
•
•
•
•
her-1,
tra-2
fem-1, 2, 3
tra-1
XO
Tra-1 is Critical
•
•
•
•
Last gene is tra-1
If Tra-1 active  herm
If not male
All others regulate
Genetic Analysis
• Tra-1 mutations suppress her-1 mutations
– Why?
• Her-1 is upstream
• Her-1 is on in males
her-1 --| tra-2 --| fem-1,2,3 --| tra-1  herm
--| male
Problems
• Herm needs to execute two programs after
gonad is made
– Make sperm
– Make eggs
Tra-2 Repression Needed for
Sperm Production
Tra-2 mRNA translation needs to be repressed in germ line
cells to get sperm
• 3’ region binds inhibitor of translation
– If delete 3’ region - herm -> female
– Escapes repression, no sperm production
• Translational repression of tra-2 by laf-1
• Laf-1 opposed by tra-3 in hermaphrodites
– Laf-1 expressed in embryo to allow construction of ovary and
again past L3 after sperm are made to allow egg production
Fem-3 Also Needed for Sperm
• Fem-3 needed for male somatic cells and germ line
differentiation
– But need to turn off to make eggs
• Fem-3 transcription inhibited by tra-2
– But leftover fem-3 mRNAs from spermatogenesis need to be
inhibited
– by binding of inhibitors (nanos, pumilio, FBF) to 3’ region to turn
off protein synthesis during egg formation in herm (L3) after
sperm are produced
C. elegans Summary
•
•
•
•
Calculation of X/A
Importance of translational controls
Cascade of interactions
Problem in hermaphrodite of forming both
sperm and egg as opposed to just the sperm
forming program