Nature of Sex Chromosomes

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Transcript Nature of Sex Chromosomes

The Nature of Sex
Ricki Lewis
Klug and Cummings
Platypus Sex Chromosome
Platypus - Echidna
Earliest type of mammal duck like bill, web feet,fur, and mammary glands
The platypus, long thought a strange creature, just got stranger
Researchers discovered that it has 10 sex chromosomes,
Some of them linked to mammals and some to birds.
Evolution of the Sex
Chromosomes - Marsupials
The Nature of Sex – The sex
chromosomes in humans
The Evolution of Y
The X and Y chromosomes diverged around 300
million years ago when some reptile, the distant
ancestor of all mammals, developed a so-called 'male
gene' - simply possessing this gene caused the
organism to be male.
The chromosome with this gene became the Y
chromosome, and a similar chromosome without it
became the X chromosome.
So initially, X and Y chromosomes were nearly
identical. Over time, genes which were beneficial for
males and harmful to (or had no effect on) females
either moved to or developed on the Y chromosome.
Recombination between X and Y
Recombination between the X and Y chromosomes
proved harmful - it resulted in males without
necessary genes formerly found on the X chromosome
 Females were found with unnecessary or even harmful
genes previously only found on the Y chromosome.
 As a result, genes beneficial to males assembled near
the sex-determining genes in order to make this less
probable. Eventually, the Y chromosome changed in
such a way as to inhibit the areas around the sex
determining genes from recombining at all with the X
The evolution of the Y
With time, larger and larger areas became
unable to recombine with the X chromosome.
 This caused its own problems: without
recombination, the removal of harmful
mutations from chromosomes becomes
increasingly difficult.
 These harmful mutations continued to damage
Y-unique genes until several finally stopped
functioning and became genetic junk; this was
eventually removed from the Y chromosome.
More about the Y chromosome
As a result of this process 95% of the human
Y chromosome is unable to recombine, the
chromosome itself contains only 83 working
 Compare this to close to 1000 working genes
on the X chromosome.
 In some animals, Y degradation is even more
severe. For example, the kangaroo Y
chromosome contains only the SRY gene
The Y chromosome
The Y chromosome
has a p and q arm
 The SRY gene
bestows the male
 The
region is on the q
Y chromosome
Short and long arm
 There are 63 pseudoautosomal genes
that cross over with the X chromosome
 Bulk of the Y chromosome is termed the
male-specific region or MSY
 The MSY lies between the two
pseudoautosomal regions
MSY and Pseudoautosomal genes
The MSY lies between the two
pseudoautosomal regions and it consista
of three classes of DNA sequences
 About 10 to 15 % of the MSY consists
of X transposed sequences that are 99
percent identical to counterparts on the
X chromosome
MSY and the other
The remainder of the MSY contains
palindrome ridden regions called
 Most of the MSY genes are vital to
Y chromosome
Although 95% of the Y chromosome lies
between the pseudoautosomal regions, fewer
than 80 genes have been found here.
 Over half of this region is genetically-barren
heterochromatin. Of the 80-odd genes found
in the euchromatin, some encode proteins
 The others encode proteins that appear to
function only in the testes. A key player in
this latter group is SRY.
The SRY encodes a transcription factor
 It sends signals to the indifferent
gonads early in the development of the
Genes on the Y chromosome
AMELY (amelogenin,Y-chromosomal)
ANT3Y (adenine nucleotide translocator-3 on the Y)
ASMTY (which stands for acetylserotonin methyltransferase)
AZF1 (azoospermia factor 1)
AZF2 (azoospermia factor 2)
BPY2 (basic protein on the Y chromosome)
CSF2RY (granulocyte-macrophage colony-stimulating factor receptor, alpha
subunit on the Y chromosome)
DAZ (deleted in azoospermia)
IL3RAY (interleukin-3 receptor)
PRKY (protein kinase, Y-linked)
RBM1 (RNA binding motif protein, Y chromosome, family 1, member A1)
RBM2 (RNA binding motif protein 2)
SRY (sex-determining region)
TDF (testis determining factor)
TSPY (testis-specific protein)
UTY (ubiquitously transcribed TPR gene on Y chromosome)
ZFY (zinc finger protein)
Human Chromosome LaunchPad
Tracing the history of the Y
indels - insertions into or deletions of the DNA at particular
locations on the chromosome. One insertion particularly useful in
population studies is the YAP, which stands for "Y chromosome
alu polymorphism." Alu is a sequence of approximately 300
letters (base pairs) which has inserted itself into a particular
region of the DNA. There have been some half a million alu
insertions in human DNA; YAP is one of the more recent.
snips - are "single nucleotide polymorphisms" in which a
particular nucleotide (an A, for example) is changed (perhaps
into a G). Stable indels and snips are relatively rare and, in the
case of the latter, so infrequent that it is reasonable to assume
they have occurred at any particular position in the genome only
once in the course of human evolution. Snips and stable alus have
been termed "unique event polymorphisms" (UEPs).
Tracing the history of the Y
microsatellites are short sequences of
nucleotides (such as GATA) repeated
over and over again a variable number of
times in tandem. The specific number of
repeats in a particular variant (or allele)
usually remains unchanged from
generation to generation but changes do
sometimes occur and the number of
repeats may increase or decrease.
Tracing the Y
The fourth polymorphism category is minisatellites,
extensively studied by Mark Jobling at the University
of Leicester. Unlike microsatellites, in which the
repeated sequences are short (often no more than 3
or 4 nucleotides),
In minisatellites they are normally 10-60 base pairs
long and the number of repeats often extends to
several dozen. Changes during the copying process
take place more frequently in minisatellites than in
microsatellites and the mechanisms may be different
in the two cases.
The Y chromosome and the
European Men
The X chromosome
Mammalian comparison
Unraveling the X
X Chromosome – related genes
Alport syndrome
Androgen insensitivity syndrome
Becker's muscular dystrophy
Centronuclear myopathy
Charcot-Marie-Tooth disease
Coffin-Lowry syndrome
Fabry disease
Fragile X syndrome
Glucose-6-phosphate dehydrogenase deficiency
Incontinentia pigmenti
Lesch-Nyhan syndrome
Menkes disease
Myotubular myopathy
Nonsyndromic deafness and X-linked nonsyndromic deafness
Ornithine transcarbamylase deficiency
Rett syndrome
Spinal and bulbar muscular atrophy
X-linked severe combined immunodeficiency (SCID)
X-linked agammaglobulinemia (XLA)
X-linked sideroblastic anemia
X and Y chromosomes
Genes on the X chromosome are
referred to as X linked
 Genes on the Y chromosome are
referred to as Y linked
X inactivation
There are two X chromosome in females
 One is inactivated early in embryological
 The inactivation is random so that only
one chromosome is active in each cell
 Females are mosaics of the X
Barr Body
The Barr Body is the
remnant of the X
Calico Cats
Sex Limited
Genes that are only expressed in one
 Antlers in male deer
 Milk production in female cows
Sex influenced
Baldness in males
 Traits that are expressed with one copy
in males and two copies in females( with
hormonal influence)
Genomic imprinting
The phenomenon of genomic imprinting is the
differential modification of the maternal and
paternal genetic contributions to the zygote,
resulting in the differential expression of parental
alleles during development and in the adult.
A disturbance in genomic imprinting in humans has
been shown to play a role in several birth defects,
genetic diseases and cancers.
In humans, the most convincing demonstration of an
imprinted region is at chromosome 15q11-q13 with a
deficiency of the maternal region resulting in the
Angelman syndrome (AS) and a deficiency of the
paternal region resulting in the Prader-Willi syndrome
Genomic imprinting
Prader Willi
short stature
small hands and feet
hypotonia and poor muscle
excess fat, especially in the
central portion of the body
narrow forehead
almond shaped eyes with
thin, down-turned lips
light skin and hair relative to
other family members
lack of complete sexual
development in adolescence
Angelman Syndrome
Angelman Syndrome
Severe developmental delay (100%)
Minimal use of words or nonverbal; receptive skills higher than expressive skills
Movement or balance disorder including, wide based gait with feet turned
outward, tremulous movement of limbs, and uncoordinated movements (100%)
Behavioral uniqueness such as frequent laughter or smiling, happy demeanor,
easily excitable often with hand flapping movements, hypermotoric behavior (can
be seen in infants as ceaseless activity), and a short attention span (100%)
Microcephaly by age 2 (>80%)
Seizures of any type by age 3 years (>80%)
Abnormal EEG (>80%)
Strabismus (20-80%)
Tongue thrusting and suck and swallow disorders (20-80%)
Feeding problems in infancy (20-80%)
Hypopigmented skin and eyes (20-80%)
Hyperactive tendon reflexes (20-80%)
Uplifted arms when walking (20-80%)
Prominent mandible (20-80%)
Wide mouth/wide spaced teeth (20-80%)