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The Genetics of Sex

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by Jennifer Dever on 22 April 2014

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Transcript of The Genetics of Sex

The Genetics of Sex
Sex Determination
Establishing Sex is a Fundamental Developmental Decision

Although most animals have two sexes (F/M) there is a great variety of mechanisms that have evolved


Sex Determination in
C. elegans
Regulatory cascade dictated by X:A
XX = hermaphrodite (sperm & eggs), XO = male (sperm)
Regulation involves intercellular signaling (Ligand-Receptor Pathway)

Sex Determination in Mammals
Much more complex, not completely understood
Determination is controlled by presence/absence of the Y chromosome
Hormonal regulation of sexual phenotype
Sex hormones bind to specific receptors, triggering gene activation
Formation of female phenotype involves secretion of estrogen from theca cells which triggers Mullerian duct differentiation;
Estrogen secreted from fetal ovaries is sufficient to induce Mullerian differentiation
Formation of male phenotype involves secretion of testicular hormones that promote Wollfian development and cause the Mullerian duct to atrophy
AMH (aka MIS)
Testosterone: promotes formation of male reproductive structures
Dihydrotestosterone - masulinizes male urethra, prostate, penis & scrotum

Genetic switch controlled by X:A
Master Switch Xol-1
OFF - Hermaphrodite
ON - Male
X:A = 1, hermaphrodite
enhanced expression of fox-1 & sex-1
FOX-1 & SEX-1 repress xol-1
sdc genes are expressed
tra genes are expressed
Genetic Switch controlled by X:A
Directive for establishing the sexual phenotype is carried out by master regulatory switch and several sex-specific genes

Master switch sxl:
Off = MALE
On = FEMALE

X:A = 1,
sxl
ON
Functional SXL protein made
-positive feedback of Sxl
-female splicing of tra
-female splicing of dsx
-female splicing of fru
Expression of female specific genes
DSX causes repression of male specific genes
Dsf is responsible for female mating behavior
Sex Determination in
Drosophila
Involves a regulatory cascade that includes alternative splicing, dictated by
X:Autosome
Every cell determines its sex independently
each cell lineage makes sexual decision
Ratio of X chromosomes to Autosomes is what determines sex (X:A)
Y chromosome not necessary for male development but is required for fertility

Some fish exhibit genetically programmed sex change during development
Gonads are dimorphic, having both female & male areas
Protogynous = female first, protandrous = male first

X:A = 0.5, sxl OFF
Nonfunctional SXL protein made
DSX represses female-specific genes
FRU responsible for male behavior
F
M
M
Genes Involved:
Sex-lethal (
sxl
)
doublesex (
dsx
)
transformer (
tra
)
fruitless (
fru
)
~25 Genes Involved:
xol-1
,
her
-1,
tra
genes,
fem
genes,
sdc
genes
fox
-1,
sex
-1

X:A = 0.5, Male
low levels of FOX-1 & SEX-1 insufficient to block expression of xol-1
sdc genes are repressed
her-1 is expressed, TRA is blocked
fems are blocked
male development occurs (egl-1, mab-3)
SRY region on Y chromosome codes for transcription factors which determine maleness (i.e. TDF binds to DNA and regulates genes controlling the development of the testis)
endocrine hormonal system involved

Primordial germ cells migrate to the genital ridge, presence of Y determines if they will organize into testes….
Testosterone will be produced, and this hormone binds to androgen receptors which function as transcription factors
In XX individuals, absence of SRY and subsequent absence of testosterone (and presence of Wt-1/Wt-4 & DAX-1) results in female pathway

http://www.ncbi.nlm.nih.gov/mapview/maps.cgi?TAXID=9606&QSTR=6736[gene_id]&QUERY=uid(34587964)&chr=Y&maps=ugHs%2Cgenes%2Cpheno-r
3 cell lineages present in gonad as well as the germ cells
1) Supporting cell lineage will give rise to Sertoli cells in testis & follicle cells in ovary
2) Steroidogenic cell lineage – produce sexual hormones
Female = theca cells
Male = Lydig cells
3) Connective cell lineage – formation of organ as whole
Each lineage has a bipotential fate

Main Genes Identified Thus Far:
Sry
Sf-1
Wt-1, Wt-4
Dmrt-1
Sox-9
Sox-8
Dax-1
Dhh
GSD (genetic sex determination)
ESD (environmental sex determination
Dosage Compensation in
Drosophila
:

in Females: (X:A = 1) SXL causes
msl-2
to be off (histone acetylation complex does not form).
in Males: (X:A = 0.5) MSL-2 present, acyeylation occurs, genes on X are hypertranscribed.
Dosage Compensation in
C
.
elegans
:
in Hermaphrodites (X:A = 1) sdc genes are ON, SDC-2 represses transcription of X genes by half
in Males (X:A = 0.5) sdc genes OFF, X genes not repressed.
Dosage Compensation in Mammals: (X inactivation)

Xic = controls chromosome counting & choice
XIST gene - produces RNA molecule that binds all over one X chromosome
Barr Body = inactive X
http://www.nytimes.com/2014/01/21/science/seeing-x-chromosomes-in-a-new-light.html?_r=0
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