Download 16 sex determination

Sex determination
Dioecious: the majority of animals exist as one of two sexes, with males
producing sperm and females producing eggs.
Sexual dimorphism: in many species, the differences between sexes are not
limited to the reproductive organs, but extend to other characteristics such as
size, ornaments, and body shape.
Monoecious: all individuals of a species look alike and produce eggs and
sperm. Common in invertebrates. Individuals with both gonads are
hermaphodites.
Sex determination: the natural
event by which an individual of a
dioecious species becomes male
or female. There are two main
mechanisms for sex determination:
Environmental sex determination:
in some species, sex is determined
after fertilization by environmental
factors (temperature, population
size, or sex of others).
Genetic sex determination: sex is
determined at fertilization by the
combination of genes that the
zygote receives.
Environmental sex determination
Sex is determined by extrinsic factors after the process of fertilization. A
variety of interesting methods influence environmental sex determination:
Chance: Bonellia verdis: a marine worm, females are large and attach to rocks
in the sea; males are small. The larvae float in the ocean. When they settle
down and land on a female worm, they become male. If they land elsewhere (on
the sea floor), they become female.
Maximize number of offspring: M. incognita is a nematode plant parasite. If
nutrients are sparse, they become males. If plentiful, the worms become
females, which enhances the reproductive potential of the population.
Social: coral reef fish may start
out as one sex but later change
to the other. The trigger may be
a social change, such as the
disappearance of a dominant
male or female.
Temperature: in many reptiles (crocodiles, turtles, and some lizards) sex is
determined by incubation temperature during a brief but specific stage of
embryogenesis. Small differences in ambient temperature have amazing
differences on sex ratio.
Map turtles: the sex ratio drops from 1
(all male) to 0 (all female) when ambient
temp increases from 28 to 30°C.
Alligators: the pattern is reversed in
alligators and lizards.
Crocodiles: a third pattern exists. The
males develop at intermediate temp.
and females develop at the two
extremes of higher of lower temp.
In many other reptiles, temperature has
no effect on sex determination.
It is not clear why the temperature is
important. Presumably, the different
temp. favors either males or females.
Genotypic sex determination
In humans, as well as most other organisms, the sex ratio always remains
close to 0.5, and it is not dependent on the environment.
In mammals, individuals are heterogametic or homogametic.
Heterogametic: human males produce two types of sperm with different sets of
chromosomes, XA and YA.
Homogametic: human females produce only one type of egg, XA.
Fertilization by XA sperm yields females, YA sperm produces males. Males are
not always the heterogametic sex. In birds, the roles are reversed and females
make two types of gametes.
Differences in sex chromosomes can occur in number rather than type: in the
roundworm, C. elegans, females are all hermaphrodites and have XXAA eggs,
and males have XOAA diploid sperm.
Arrhenotoky (arrhen = male, tokos = childbirth): females arise from fertilized
eggs whereas males develop from unfertilized eggs. This method is common in
bees, ants, and wasps.
Houseflies do not have distinct sex chromosomes, but they have a specific
gene that encodes sex determination (m/m is female and m/M is male).
Genotypic sex determination systems are diverse!
Dosage compensation occurs by X chromosome inactivation
What is X chromosome inactivation?
X chromosomes contain many genes that are unrelated to sex determination,
but that are not present on the Y chromosome. A double dose of these genes in
females presents a potential imbalance in levels of gene expression. It could be
harmful.
Barr body: mammals achieve balance by inactivation of one of the two X
chromosomes. This occurs in almost all cells of females at the blastopore
stage.
Are all genes on the 2nd X chromosome inactivated?
Pseudoautosomal region: a few genes in the second X chromosome escape
inactivation. They belong to a region that is very similar to the Y chromosome.
How does inactivation occur?
X-inactive specific transcript (XIST): a product of an X-linked gene that is
necessary and sufficient to inactivate one X chromosome. Initially, XIST is
transcribed from both X chromosomes. When transcribed, the mRNA binds to
the X chromosome, making it inactive for transcription of other genes. Once
the decision is made to inactivate one of the X chromosomes, it continues to
produce XIST while the active X chromosome does not.
What causes males and females to develop differently?
Testis determining factor (TDF): maleness in mammals depends on the Y
chromosome. Thus, some gene(s) encoded by this chromosome must direct
development of the testis. Where and when does TDF act?
Gonad development: gonads develop from two major cell types.
Mesoderm forms the genital ridge on the mesonephros
Primordial germ cells migrate to the future site of the gonad from the yolk sac.
The mesoderm of the genital ridge proliferates and surrounds the germ cells by
the 6th week in humans, forming the primitive sex cords. The gonad is
undifferentiated at this point. TDF acts on the undifferentiated gonad.
TDF acts on supporting cells, not germ cells
The indifferent gonad has germ cells plus 3 types of somatic cells:
1.
Supporting cells: arise from the primitive sex cords and become Sertoli
cells in testes and follicle cells of the ovaries.
2.
Steroidal cells: differentiate to produce gonadal hormones. These are
Leydig cells in males and thecal cells in females.
3.
Connective tissue cells: form the structural framework of the gonad.
The initial change in the gonad occurs in the supporting cells and not the germ
cells. Thus, the TDF does not act directly on germ cells to induce gonadal
differentiation. It acts on the supporting cells to set up the proper environment
for differentiation into sperm or egg.
Supporting cells determine development of germ cells
TDF is only expressed in cells with the Y chromosome. Expression induces the
supporting cells to become Sertoli cells and to to form testis cords. In this
environment, meiosis of the germ cells is inhibited and they slowly develop
into spermatogonia.
TDF is not expressed in cells with
only X chromosomes. Supporting
cells develop according to the
default mode as follicle cells. In
this environment, germ cells start
meiosis and produce oocytes very
early in embryogenesis (12 weeks
in humans).
The oocytes further stimulate
follicle development.
Chimeric mice (male and female
cells) can have XX sperm or XY
oocytes, but they always have XX
supporting cells in females and
XY supporting cells in males.
Supporting cells rule sex.
Mapping and cloning TDF
The critical breakthrough for mapping TDF
on the Y chromosome came from
individuals whose sex did not match their
genotype.
Sex reversed males had 2 X chromosomes
and sex reversed females had an X and Y
chromosome.
The origin of sex reversed individuals can
be explained by rare crossover events
between the X and Y chromosomes during
meiosis in the male gametes.
If the region encoding the TDF gene is
switched, it is possible to develop an X
chromosome with TDF and a Y
chromosome with no TDF. Pairing a normal
and mutant X chromosome creates a male
with a female genotype, and pairing of
mutant Y with X creates a female with a
male genotype.
Exactly what is the TDF gene(s)?
Hybridization with sex chromosome-specific DNA probes
localized the DNA involved in crossover
To localize and identify the gene that encoded TDF, fragments of DNA from the
Y chromosome were used as probes to search for TDF in sex reversed males.
DNA was isolated from tissues of normal males, normal females, and 4 different
sex reversed males. P-32 labeled fragments of Y chromosomes (not
pseudoautosomal) were used as probes to hybridize to each type of DNA.
As expected, most probes did not cross react with either normal females or the
4 sex reversed males.
However, one fragment (35 kb)
did cross react specifically
with each of the sex reversed
males but not the normal
female.
This result provides strong
circumstantial evidence that
this DNA encodes the gene for
TDF. There was only one gene
encoded on this fragment of
DNA, SRY.
SRY was also found mutated
in sex reversed females.
The mouse SRY gene is sufficient for testes formation
To prove that the SRY gene was the key to maleness (TDF), transgenic mice
were constructed that contained SRY in all cells. Fertilized eggs were injected
with the SRY gene and allowed to develop in foster mothers.
Of 3 XX transgenic mice that were born, 2 were females and one was a sex
reversed male. This male was similar in size to the other XY males, it had
normal male genitals, and it copulated with females. However, it was sterile.
Thus, SRY was sufficient to
induce sex reversal in
female mice!
The testes were normally
developed, but there were no
germ cells undergoing
spermatogenesis.
male
Sex reversed male
The reason why only 1/3 of
mice were sex reversed is
unclear (technical problems
with transgenic experiments
or additional genes might be
important).
Hormonal control of sex differentiation in mammals
Primary sex differentiation:
mammalian sex determination is
controlled by the SRY gene. SRY
expression induces testes, lack of
SRY results in ovaries.
Secondary sex differentiation:
refers to all hormonally controlled
sex development beginning at
embryogenesis and progressing
into adulthood. This includes sex
characteristics such as external
genitalia, breasts, body build, and
behavior.
Most sex hormones are steroids
derived from cholesterol. These
include androgens (testosterone
and DHT) and female sex
hormones (estrogen and
progesterone).
The gonads are the sites of synthesis for sex hormones
Testosterone is synthesized in the Leydig cells of the testes.
Estrogens are produced via the thecal and granulosa cells in the ovary.
The adrenal glands also synthesize sex hormones.
Testosterone and estrogen stimulate secondary sex characteristics such as
larger muscles in males or breasts in females.
Testosterone acts on a portion of the mesonephros called the Wolffian duct
to form the epididymis, ductus deferens, and seminal vesicle.
Estrogen acts on the Mullerian duct to convert it into oviduct, uterus, and
upper vagina.
Female external genitalia develop as the default program. If
dihydrotestosterone (DHT) is present, there will be male external genitalia. If
DHT is absent, female genitalia are the result.
Overview of somatic sexual development in mammals
Once the embryonic gonads develop as either testes or ovaries, all
subsequent steps of sexual reproduction are controlled by sex hormones.
After 6 weeks of gestation, Mullerian and Wolffian ducts exist near the
genital ridge and kidney.
Testosterone and AMH (anti Mullerian hormone) act on the Wolffian duct to
remodel it into epididymis (where sperm mature), ductus deferens
(transport sperm), and seminal vesicle
(where seminal fluid is stored). The
Mullerian duct degenerates.
In females the default program occurs. The Mullerian duct gives rise to the
oviduct (connects ovary to uterus), the uterus (where the embryo develops),
and the upper portion of the vagina. The Wolffian duct degenerates due to a
lack of AMH and testosterone.
Androgen insensitivity syndrome
This condition confirms the important role
for sex hormones in development of
secondary sex characteristics.
This syndrome is caused by a mutation in
the gene encoding the androgen receptor.
The gene resides on the X chromosome.
Males who inherit this condition produce
testosterone and DHT but they are unable to
respond to either hormone. Hence, they
develop as phenotypic females.
These individuals have normal male
chromosomes. The low level of estrogen
that is produced by the adrenal glands is
enough to stimulate female secondary sex
characteristics.
Male and female genitalia develop from the genital tubercle
Indifferent stage: at 6 weeks of
gestation the genitalia have not
been determined. Urethral folds
on both sides of a urogenital
sinus unite to form the genital
tubercle, the precursor of the
genitalia.
In females, it forms a clitoris and
the 2 folds form the labium
minora.
In males, the folds fuse in the
middle to form the penis.
Dihydrotestosterone is the steroid
that controls which pathway is
followed.
Sex hormones control development of the brain
Males and females of any species usually differ in complex behaviors such as
mating, parenting, and aggression. How does this occur?
For each sex hormone, there is a unique distribution of receptors throughout
the brain. Androgen receptor is concentrated in areas that control aggression
and mating. Estrogen receptors are concentrated in areas that control
ovulation.
Songbirds are a good example. Male birds attract females by singing, and the
songs are learned from older males. If male birds are castrated, the amount
and quality of their singing decreases. If they are subsequently treated with
testosterone, singing resumes. Specific areas in the brain of male birds that
are associated with singing are larger than in female birds.
Interesting effects of sex hormones are seen in mammals that produce
litters of multiple offspring. The growing fetuses exchange sex hormones
via the placental circulation.
Females that develop between 2 males (2M females) are exposed to higher
levels of testosterone than siblings that develop next to 1 or no males.
These 2M females have masculinized genitals, have shorter reproductive
cycles, and are less attractive to males.
The converse effects are observed in males that develop next to 2 females.
They have smaller seminal vesicles and are less aggressive than 0F males.
baby boars
Subtle differences in non reproductive behavior are suggested by different
distributions of scores on standardized tests. Men tend to score higher on
manipulating 3D images and mathematical reasoning. Women score better
on tasks related to precision, verbal use, and perceptual speed.