1. Genetics of Sex Sex Determination Evolution of Sex Chromosomes
In Drosophila
In C. elegans
In mammals
Evolution of Sex Chromosomes
X & Y were once just another autosome…
Comparison of X & Y
X Inactivation

2. I. Sex determination mechanisms
Although most animals have two sexes (M/F) there is a great variety of mechanisms that have evolved
GSD
X:A
XX/XY
ZW/ZZ
ESD

3. Sex Determination: A. in Drosophila
Every cell determines its sex independently
Ratio of X chromosomes to Autosomes is what determines sex

4. Early in embryonic development, a cascade of differential (alternate) mRNA splicing results in either female or male.
The three branches of the hierarchy govern:
X chromosome dosage compensation
somatic sexual differentiation
male sexual behavior

5. = 1
= 0.5

7. B. C. elegans – hermaphrodites or males?
Like Drosophila,

8. 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.

9. C. Sex determination in mammals
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

10. Gonad is bipotential
3 cell lineages present in gonad as well as the germ cells
Supporting cell lineage will give rise to Sertoli cells in testis & follicle cells in ovary
Steroidogenic cell lineage – produce sexual hormones
Each lineage has

11. This is divided into 3 regions:
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.

12. Transcriptional control is mechanism for switch

14. II. Evolution of the X & Y Evolved 300 mya, autosomal origin
A. X & Y were once just another autosome…
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

15. Autosomal origin of X supported by orthologous regions from Chicken, 30 regions of homology illustrated:

16. B. Comparison of X & Y
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

18. III. X Inactivation Dosage compensation mechanism in mammals
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