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

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

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: 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 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 Supporting cell lineage will give rise to Sertoli cells in testis & follicle cells in ovary Steroidogenic cell lineage – produce sexual hormones Each lineage has

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.

Transcriptional control is mechanism for switch

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

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

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

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 http://www.hhmi.org/biointeractive/animations/x_inactivation/xinact_frames.htm