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 3 2/3 (0.67) male

XXX 4 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 XO

• her-1,
• tra-2
• fem-1, 2, 3
• tra-1
 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