Sex

Determinati
on in
Mammals

Sex Determination

PRIMARY

SECONDARY

Gonads

Phenotype beyond
gonads

Strictly
chromosomal,
no environmental
effect

Sex hormones

Primary Sex Determination

Presence of Y chromosome key for
determining maleness
Klinefelter Syndrome
Syndrome

Turner

The Y Chromosome
Sex-determining Region of the Y
chromosome (SRY) encodes
Testis Determining Factor (TDF):
223 residues, DNA binding
domain
Transcription factor for other
maleness genes (e.g. SF1)

SRY is key for maleness

SRY transgenic XX
mice develop as males

Translocations

The Bipotential Gonad

No SRY gene:
Gonads develop into
ovaries
Ovaries release
estrogen
Estrogen develops
Mllerian duct
oviduct and uterus

The Bipotential Gonad

SRY gene transcribed
to TDF:
Gonads develop into
testes
Testes release
testosterone
Testosterone develops
Wolffian duct vas
deferens and
epididymis

Sex Reversal Genes: DAX1

SRY antagonist
Overrides
maleness!

Sex Reversal Genes: SOX9

Autosomal gene
Gene duplication in XX male
Inactivating mutation in XY female
Haplosufficient or haploinsufficient?
Message: SOX9 presumably necessary and
sufficient for maleness (regardless of
presence of SRY)
Sox9 is found in all vertebrates but Sry is
not. Does this make sense evolutionarily?

Summary of Sex Determining Genes

Androgen Insensitivity
Syndrome

A secondary sexual defect

Individuals XY w/ a functional SRY gene
Mutation in an AR gene (X-linked),
testosterone receptors not
present/functional
No physiological response to testosterone
Aromatase converts testosterone to
estrogen
Individuals will develop female secondary
sexual characteristics

Androgen Insensitivity
Syndrome
Male or Female?

Exam Questions
During DNA replication in a female meiocyte, the
Dax1 gene is accidentally duplicated on one of the
X chromosomes. The cell undergoes meiosis, and
one of the resulting gametes combines with a
normal sperm. What is the predicted ratio of males
to females in the offspring?
An XY mouse embryo contains a mutation at the
Sox9 locus. Such a mutation will make the mouse
phenotypically female. If exogenous SRY gene was
introduced into the organism before gonad
differentiation, would the mouse still develop as
female?