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Sex Chromosomes
Chapter 5
1
Outline
• Sex chromosomes
• Sex determination
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Role of Y Chromosome
3
Klinefelter and Turner Syndromes
XXY
XO
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47, XXX Syndrome
• Also called triploid-X or triplo-X
• Many times results in normal female
• Extra X can create reproductive issues,
development, language, etc.
Note: Humans very intolerant of 3rd copy
of
autosomes
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47, XYY Condition
• Males over 6 feet tall
• High correlation with behavioral problems
(prison studies)
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Human Y Chromosome
Protein coded this gene acts as
“transcription” factor binding to DNA
and causing fetus to develop testes
27 distinct protein-coding genes
12 are exclusively expressed
in testes
95% length
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The Y-Chromosome
Y has not lost any of the genes
shared with chimps since
Human line divergence 8-10 MYBP
In fact only lost one gene since Great Apes split from
Monkeys
Inheritance of Y-Chromosome
Y-Adam lived 50,000 to 150,000 years ago
(46, XaiY)AIS: Androgen Insensitivity Syndrome
X-linked recessive (Xq11-12)
(genetically male, phenotypically female)
• Androgen hormone
interaction with the
Androgen receptor
early in fetal tissue
development regulates
proper development of
genitals.
46 XAIXai and XaiXai no effects
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Barr bodies
• Dosage compensation
• X-chromosome inactivation
• 15% of X-chromosome genes escape inactivation
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Karotypes with extra X Chromosomes
have extra Barr Bodies
Norm male
Turner’s
Syndrome
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Norm female
Klinefelter Syndrome
Lyon Hypothesis
• X-chromosome inactivation occurs randomly in
somatic cells in early embryonic development
• Can lead to mosaic expression as in female
calico cats
Calico / tabby
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Some cat fur color genes are X-linked
When an X-chromosome is Inactivated, all its subsequent
daughter cells are similarly inactivated
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Mechanism of X-inactivation
• Epigenetic memory – daugher cells of silenced cells are
also silenced
• XIC on inactivated X chromosome encodes the Xist gene
• RNA transcribed from Xist gene silences X-chromosome
genes
q arm
H
Y
P
E
R
M
E
T
H
L
A
T
E
D
Active Inactive
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Mechanism of X-inactivation
• Xist is RNA gene (no protein coded) and is part of
“XIC” X-Inactivation Center along with 2 other RNA genes
and two protein-coding genes
q arm
H
Y
P
E
R
M
E
T
H
L
A
T
E
D
Active Inactive
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Mechanism of X-inactivation
Becomes Barr Body;
Barr Body Duplicates
Later in S-phase of
Cell cycle than active X
q arm
Active Inactive
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The Inner Cell Mass will
consist of cells that are
Pre-XCI, XCI and some
never XCI
Days, weeks and months
Post conception
Random XMXP
in females
Except germ cell
production
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When a cell Inactivates One Of Its Two X-Chromosomes,
All Subsequent Daughter Cells Will Carry the Same
XM vs XP Inactivation
43 of the 233 X-linked genes escape inactivation. Some of these
are in the “PAR” region, others do not have Y-equivalents, many
on the short “p” arm.
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P
R
O
T
O
Without X-Inactivation
X-Chromosome Transcript
of males would be half that
of females
X
100 million years of mammalian evolution
P
R
O
T
O
X
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P
R
O
T
O
Without X-Inactivation
X-Chromosome Transrcipt
of males would be half that
of females
X
100 million years of mammalian evolution
P
R
O
T
O
X
Gradual Incremental X-Inactivation
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Concept: The evolutionary pressure for the Y chromosome dictated need to suppress
one of the two X chromosomes.
Why?
I like the hypothesis which starts with "the mammalian X and Y chromosomes
evolved from a pair of autosomes (widely accepted)." As the developing or
evolving Y acquired its sex-determining region (authors below describe
the evolutionary pressures) it slowly lost the genes on the "proto-X chromosome."
With each evolutionary step toward a more specialized Y chromosome a bit more
of proto-X's genes were lost. The evolutionary response to maintain gene dosage
was up-regulation of "un-partnered" genes on the X chromosome.
Over more than 100 million years of mammalian evolution the Y chromosome
became highly specialized in infinitely small subtle evolutionary steps.
To compensate for the increasing up-regulation, one of the X-chromosomes in
females (XX) needed to be silenced. Hence, X-inactivation. It too probably
evolved in small evolutionary steps.
https://www.musc.edu/mbes-ljg/Courses/Biology%20of%20Reproduction/
Paper%20pdfs/Waters%20Wallis%20Graves%202007.pdf
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