Transcript Genetics of Sex - University of San Francisco

Genetics of Sex
Sex Determination
I.
A.
B.
C.
Evolution of Sex Chromosomes
II.
A.
B.
III.
In Drosophila
In C. elegans
In mammals
X & Y were once just another autosome…
Comparison of X & Y
X Inactivation
I. Sex determination mechanisms


Although most animals have two sexes (M/F)
there is a great variety of mechanisms that
have evolved
GSD

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
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X:A
XX/XY
ZW/ZZ
ESD
Sex Determination:
A. in Drosophila

Every cell determines its sex independently

Ratio of X chromosomes to Autosomes is
what determines sex
Early in embryonic development, a
cascade of differential (alternate) mRNA
splicing results in either female or male.
The three branches of the hierarchy govern:

1)
2)
3)
X chromosome dosage compensation
somatic sexual differentiation
male sexual behavior
=1
= 0.5
B. C. elegans – hermaphrodites or males?

Like Drosophila,
X:A = 1, enhanced expression of fox-1 & sex-1 whose products inhibits the
expression of xol-1. sdc genes are expressed, which are involved in dosage
compensation and hermaphodite development.
C. Sex determination in mammals


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Not independent for each cell
Not as simple a pathway as Drosophila or C.
elegans… not yet completely understood
Sex is determined by the presence or absence of the Y
chromosome
Gonad is bipotential

3 cell lineages present in
gonad as well as the germ cells
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Supporting cell lineage will give
rise to Sertoli cells in testis &
follicle cells in ovary
Steroidogenic cell lineage –
produce sexual hormones
Each lineage has
Mammalian gonad forms within the developing urogenital system, which
itself derives from the intermediate mesoderm.
This is divided into 3 regions:
Epithelial structures are shown in red, mesenchymal structures are shown in blue,
and the striped region denotes the genital ridge. (WD) Wolffian duct; (MT)
mesonephric tubules; (MD) Mullerian duct; (UB) ureteric bud; (CE) coelomic
epithelia.
Transcriptional control is mechanism for switch
II. Evolution of the X & Y
A. X & Y were once just another autosome…


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Evolved 300 mya, autosomal
origin
X – 1,098 genes (lowest #
compared to autosomes)
4,493 ECRs conserved between
human, mouse, rat, zebrafish &
pufferfish
Males Hemizygous –
X linked inheritance
Autosomal origin of X supported by orthologous regions from Chicken,
30 regions of homology illustrated:
B. Comparison of X & Y
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Y significantly smaller than X, few
genes shared between the two
In the Y chromosome, the shutting
down of X–Y crossing over during
evolution triggered a monotonic
decline in gene function
PAR1 homology maintained by
recombination in male meiosis,
genes in this region not subject to
dosage compensation
III. X Inactivation

Dosage compensation mechanism in mammals
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Mammalian cells have ability to count their X chromosomes
 X inactivation center (Xic) plays critical role
Xist (located in Xic) expression required for compaction of X into a
Barr body
X chromosomal controlling element (Xce) & TsiX affects the choice
of which X to be inactivated
About 15% of the genes escape effects of X inactivation
 Xist
 Pseudoautosomal genes also found on Y
 Female sex-specific genes
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http://www.hhmi.org/biointeractive/animations/x_inactivation/xinact_frames.htm