Mary Lyon hypothesis: Inactivation of all but one X
chromosome (dosage compensation). This allows the dosage relationship
between # X and # autosomes to be the same in males and females. Females
(XX) do not express a sex-linked trait more markedly than hemizygous males
X Y).
Only one X chromosome required for cell to function other X chromosomes (1 in normal individuals) are
inactivated (more dense and stain darker).
Because X chromosome inactivation does not normally occur
in the very early developmental stages of germ cells, each ovum
still receives an X chromosome from the female parent.
Because approximately 15 % of X chromosome genes may escape
inactivation, sex chromosome aneuploid individuals (ex. XXY
and XXX ) can be affected by the over-expression of X chromosome
genes.
Homozygous: Ex. XAXA XaXa
Heterozygous: Ex. XAXa
Hemizygous: Having only one allele of a given gene.
Ex. XAY XaY
Mosaic phenotypes in three generations of females, all heterozygous for the X-linked
gene for ectodermal dysplasia. Stippling indicates areas in which sweat glands are
missing. The affected areas differ in each woman because the controlling gene is
inactivated randomly, even in the identical twins in generation III.
I
II
III
The inactivation of X chromosomes during development apparently occurs at random.
Early in development, the maternally-derived X is inactivated in some cells, while the
paternally-derived X is inactivated in others. Thereafter, descendants of a particular cell
have the same X inactivated. If a female is heterozygous for an X-linked gene, she is
mosaic for that trait. One of her X chromosomes is active in roughly half of her cells,
while the second X is active in her other cells.
Euploid
Having a chromosome number that is an exact multiple
of the haploid number.
Aneuploid
Having an abnormal number of chromosomes-usually the addition or loss of
one or two chromosomes. Not having a number that is a multiple of the
haploid. Autosomal-ex. Trisomy 21 (Down’s Syndrome).
Sex Chromosomal-ex. Turner’s and Klinefelter’s Syndromes.
Polyploid
Having more that two homologous sets of chromosomes
(more that 2N; ex. 3N, 4N, etc.)
Human sex chromosome
aneuploids
• 47, XXY – Klinefelter’s syndrome – One
Barr body.
• 45, XO – Turner’s syndrome – No Barr
bodies.
• 47, XXX – Super female – Two Barr
bodies.
• 47, XYY – Super male – No Barr bodies.
Model for sex determination in
mammals
• In the article “Zeroing in on the Sex Switch” that
reports the work of David Page, the gene detected
on the X chromosome that appeared similar to that
of the SRY gene on the Y chromosome, may have
been the NR0B1 gene.
• In association with the Lyon hypothesis, in which
all but one X chromosome is inactivated to a Barr
or chromatin body, an interplay between SRY and
NR0B1 genes determines sex.
Sex-determining region Y (SRY) gene
•
•
•
•
This has been positively identified as the gene encoding the testisdetermining factor (TDF). When injected into normal (XX) female
mice, it caused them to develop as males. The gene acts via two
established mechanisms:
1) The SRY protein (TDF) binds the p450 aromatase gene and inhibits
its activity. The p450 aromatase gene has a protein product that
converts the male hormone testosterone to the female hormone
estradiol.
2) The SRY protein (TDF) enhances the activity of the gene for
MÜLLERIAN-INHIBITING SUBSTANCE (MIS). MIS induces testicular
development and the digression of female reproductive ducts.
Thus, the SRY protein (TDF) points an indifferent embryo toward
maleness and the maintenance of testosterone production. This major
sex switch initiates a developmental sequence that ultimately involves
numerous genes.
PGC’S (Primordial Germ Cells; bipotential)
6 weeks (humans)
1 NR0B1 gene (DAX1) on 1
active X chromosome (XX ind.),
1 SRY gene (TDF) on Y
or 1 SRY gene (TDF) on Y
chromosome and 1NR0B1 gene
chromosome and 2 NR0B1
6-16 (DAX1) on X chromosome.
genes (DAX1) on X
weeks (sexual
chromosome (XY ind.)
differentiation)
Mullerian Duct System
(inc. ovaries)
Wolffian Duct System
(inc. testes)
Lack of male sex hormone and
presence of female sex hormone
from ovary stimulates development
of 2º sexual organs and
characteristics ( ).
Presence of male sex hormone from
testis stimulates development of 2º
sexual organs and characteristics
(
).
Problems in sex hormone secretion in accordance with genetic sex
may cause genotypic and phenotypic sex contrast.
XX = homogametic sex
XY = heterogametic sex
In some organisms [birds (chickens), moths, and some
fish], the relationship between X and Y is reversed in
comparison to that in mammals.
♂ (male) rather than ♀ (female) is the
homogametic sex [XX (ZZ)] in
these organisms.
♀ (female) rather than ♂ (male) is the
heterogametic sex [XY (ZW)] in
these organisms.
Gyandromorphs and Chimeras
• Gyandromorph: An individual that developed
from a single fertilized egg (embryo) and which is
composed of both male and female genotype cells
(sexual mosaic).
• Chimera: An individual formed from two different
cell lines or the fusion of two non-identical
fertilized eggs (embryos), but which is composed
of cells that all have the genotype of one sex (male
or female).
Hermaphrodite
An individual that possesses both male and
female gonads, with the social
environment usually controlling whether
the individual takes on a male or female
reproductive role.
Drosophila melanogaster
Bilateral Gyandromorph
“Sexual Mosaic”
2A2X
Mitotic non-disjunction
XW XW
Xw Xw
1) 2A 3X
- metafemale
2) Red eye
- XWXWXw
3) No sex comb
4) Light abdomen
11
11
11
11
11
11
1) 2AX0
- sterile male
2) white eye
- Xw0
3) Sex comb
4) Dark abdomen