Transcript sex_chromosomes

Chapter 04
Lecture Outline
Copyright © 2016 McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.
1
2
What is true about sexual reproduction?
a. Each parent contributes a haploid gene set to
offspring.
b. Sexual reproduction consists of mitosis only.
c. Sexual reproduction involves the union of
diploid gametes.
d. Sexual reproduction produces a haploid
zygote.
e. All of the above.
4.1 Mechanisms of Sex Determination
Among Various Species

Different mechanisms of sex determination
4
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Sex determination and sex chromosomes
• Sex determination is the mechanism by which an
individual develops into a female or a male
• In many species, the process relies on sex
chromosomes that are different in males and females
– for example, X and Y
• Other mechanisms exist as well
– Environmental (temperature)
– Behavioral interactions
5
X-Y sex determination
44 +
XY
• Found in mammals, including humans
• Male is X-Y – the heterogametic sex
– Two kinds of sperm are produced
– Either X or Y plus 22 autosomes
• Female is X-X – the homogametic sex
– All eggs are the same, with X
– X plus 22 autosomes
44 +
XX
+
• The sperm determines the sex of the zygote
6
A human with an XY chromosome pair appears
female. What might explain this person’s
condition?
a.
b.
c.
d.
e.
This person suffers from Turner syndrome.
This person suffers from Klinefelter syndrome.
This person has a mutated Sry gene.
This person has an extra copy of the Sry gene.
The XY determination was an error because it is
impossible for a human XY individual to be female.
X-Y sex determination
• The Y chromosome promotes male development
– How do we know that two Xs do not directly
promote female development?
• Because XXY individuals are male
• and X0 individuals are female
• A single gene on the Y chromosome is responsible for
male development – the Sry gene
8
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
X-0 sex determination
• Found in many insects, such as
grasshoppers
• Male is X-0 (has just one X
chromosome)
– Some insects have XY males (ex:
Drosophila)
• Female is X-X
22 +
• In this system (even with XY males), it XX
is the ratio of X chromosomes to
autosomes that determines sex
– 1 X / 2n autosomes is male
– 2 X / 2n autosomes is female
22 +
X
9
Z-W sex determination
• Found in birds and some fish
76 +
ZZ
• Male is Z-Z – the homogametic sex
• Female is Z-W – the heterogametic sex
76 +
ZW
10
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Haplodiploid sex determination
• Sex is determined by the number of
sets of chromosomes
• Found in bees, wasps, and ants
• Example: The honeybee
– The male (a drone) is produced from
unfertilized eggs
that are haploid – one set of 16
chromosomes
– The females (workers and the queen) grow
from fertilized eggs that are diploid – two
chromosome sets, 32 total
– So only the female arises through
sexual reproduction
© Scott Camazine/Photo Researchers
Male honeybee (Drone)
Haploid – 16 chromosomes
© Photo by Rob Flynn/USDA
Female honeybee
Diploid – 32 chromosomes
11
Temperature-dependent sex determination
• Found in some reptiles and some fish
• Example: the American alligator
– Eggs incubated at 33oC grow into males
– If eggs are incubated a few degrees below or above
33oC, they grow into females
– Male and female alligators have the same
chromosome composition
12
Behavioral sex determination
• Behavioral interactions can determine sex
• Example: Clownfish (Amphiprion)
– Protandrous hermaphrodites – switch from male to female
– Many fish live in each anemone – one female, one male, and many
small juveniles
– When the large female dies, the male switches sex to take over the
female role, and one juvenile becomes a male
– Male and female clownfish have the same chromosome composition
13
Dioecious Plants
• Most plants produce both male and female gametes
from the same individual – called monoecious
– But some plants are dioecious – each individual
plant is either male or female
• Examples: Holly, willow, and ginkgo
• Example: White campion, Silene latifolia
– Males are XY, females are XX
– But for other species, cannot recognize different sex
chromosomes, so mechanism is mysterious
© Rolf Nussbaumer Photography/Alamy
(a) American holly (I. opaca)
Female
Male
© Arco Images GmbH/Alamy
© Arco Images GmbH/Alamy
14
(b) Female and male flowers on separate individuals in white campion
(S. latifolia)
4.2 Dosage Compensation
and X-Chromosome
Inactivation in Mammals



How dosage compensation is achieved in different animal
species
X-chromosome inactivation in mammals
How X-chromosome inactivation may affect the phenotype
of female mammals
15
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Dosage compensation
• Important genes lie on the X chromosome
– Many of these encode proteins that interact with proteins
encoded by autosomal genes
• How do both females and males keep the levels of
X chromosome genes in balance with the levels of
autosomal genes?
• Dosage compensation – the mechanism that keeps
levels of expression of X chromosome genes in balance
with those of autosomal genes for both sexes
16
• Dosage compensation mechanisms vary for different species
– Some - increased expression in heterogametics (XY)
• Example: Drosophila males increase X expression
– Others - decreased expression in homogametics (XX)
• Example: C. elegans females lower X expression
• X-Chromosome inactivation (XCI) is another way to do this, used
by mammals
17
18
X chromosome inactivation
• Mary Lyon, 1961
– Proposed that female mammals
inactivate one of their X
chromosomes in each somatic cell
• The X is chosen at random in
different cells early in
development, then maintained
– Known as the Lyon Hypothesis
– Evidence:
• Barr and Bertram saw
condensed structure in somatic
cell nuclei – the Barr body
• Female mammals often exhibit
variegation
– Such as calico cats
Barr
body
Active
X-chromosome
Barr
body
19
White fur
allele
Black fur
allele
b
B
Early embryo—
all X chromosomes
active
b
B
b
b
B
B
b
b
B
B
b
b
B
b
B
B
Random X chromosome
inactivation
Barr bodies
b
B
B
b
b
B
b
B
b
Further
development
Mouse with
patches of
black and
white fur
20
X-chromosome inactivation
• Human individuals that are not 46 (XY) or 46 (XX) still
have only one active X chromosome
– Klinefelter syndrome – XXY; one Barr body
– Turner syndrome – X0; no Barr body
– Triple X syndrome – XXX; two Barr bodies
• What is the mechanism to “count” the number of X
chromosomes in cells?
21
X-inactivation center and Xist
• Mechanism of counting relies on a region of the Xchromosome called the X-inactivation center (Xic)
– Contains the X-inactive specific transcript (Xist) gene
– Xist is active on the condensed chromosome in Barr body
• Three phases for inactivation
1. Initiation – X-chromosome is selected for inactivation
2. Spreading
• Xist expressed on chromosome to be inactivated
• Xist transcripts coat chromosome
• Proteins recruited to chromosome to condense it
3. Maintenance through mitosis and beyond
22
To be
inactivated
Xic
Xic
Initiation: Occurs during embryonic development.
The number of X-inactivation centers (Xics) is
counted and one of the X chromosomes remains
active and the other is targeted for inactivation.
Xic
Spreading: Occurs during embryonic
development. It begins at the Xic and
progresses toward both ends until the
entire chromosome is inactivated. The
Xist gene encodes an RNA that coats the
X chromosome and recruits proteins that
promote its compaction into a Barr body.
Xic
Further
spreading
Barr
body
Maintenance: Occurs from embryonic
development through adult life. The
inactivated X chromosome is maintained
as such during subsequent cell divisions.
23
4.3 Properties of the X and Y
Chromosomes in Mammals

Features of the X and Y chromosomes in mammals

How pseudoautosomal inheritance occurs
24
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Properties of mammalian X and Y
• Some genes are unique to X or Y – sex-linked genes
– Those on X only are called X-linked
– Those on Y only are called Y-linked or holandric
– Inheritance patterns different than autosomal genes
• Pseudoautosomal genes are found on both X and Y
– Inheritance patterns similar to autosomal genes
• Some regions of X and Y without genes share homology
– Help in pairing X and Y chromosomes during meiosis I
Mic2 gene
X
Mic2 gene
Y
25
4.4 Transmission Patterns
for X-Linked Genes


Morgan’s experiment localizing an eye color gene
to the X chromosome
Crosses involving X-linked genes
26
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Inheritance patterns of X-linked genes
• Inheritance patterns of X-linked genes differ from autosomal
genes
– Called X-linked inheritance
• Fathers transmit the X only to daughters, and sons receive
their X only from their mothers
• A male is said to be hemizygous for X-linked genes
– As opposed to homozygous or heterozygous
– Since there is only one copy
27
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Morgan’s Experiments with Flies
• The Chromosome Theory of Inheritance was confirmed by
Thomas Hunt Morgan in the early 1900s
– He confirmed that a particular gene was localized to a
chromosome
• Morgan induced eye color mutations in Drosophila
melanogaster
– Obtained a white-eyed fly (rather than normal red)
• Called the new mutation white
– He studied its inheritance pattern after breeding with red-eyed flies
28
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Conceptual level
Experimental level
XwY x Xw+Xw+
1. Cross the white-eyed male to a
true-breeding red-eyed female.
x
2. Record the results of the F1 generation.
This involves noting the eye color and
sexes of many offspring.
Xw+Y male offspring and Xw+Xw female
offspring, both with red eyes
Xw+Y x Xw+Xw
x
F1 generation
1 Xw+Y : 1 XwY : 1 Xw+Xw+ : Xw+Xw
1 red-eyed male : 1 white-eyed male :
2 red-eyed females
3. Cross F1 offspring with each other to
obtain F2 offspring. Also record the
eye color and sex of the F2 offspring.
F2 generation
4. In a separate experiment, perform a
testcross between a white-eyed male
and a red-eyed female from the F1
generation. Record the results.
XwY x Xw+Xw
x
From
F1 generation
1 Xw+Y : 1 XwY : 1 Xw+Xw : XwXw
1 red-eyed male : 1 white-eyed male :
1 red-eyed female : 1 white-eyed female
29
The Data
Cross
Results
Original white eyed-male F1 generation:
to red-eyed females
All red-eyed flies
F1 male to F1 females
F2 generation:
2,459 red-eyed females
1,011 red-eyed males
0 white eyed-females
782 white-eyed males
Test Cross
Results
White-eyed males to
F1 females
Testcross:
129 red-eyed females
132 red-eyed males
88 white eyed-females
86 white-eyed males
30
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Interpreting the Data
• White eyed male crossed to red eyed female produced all
red-eyed flies in F1
– Conclude that red eye is dominant
• If gene is autosomal can predict that in F2
(from cross of the F1 generation flies) should get
– 75% males with red and 25% with white eyes
– 75% females with red and 25% with white eyes
– 3:1 ratio overall of red-eyed to white-eyed flies
• BUT – he got zero white-eyed females!
31
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
As with autosomal genes, a Punnett square can be used to predict the
outcome of a mating if a gene is sex-linked
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
F1 male is Xw+Y
F1 female is Xw+Xw
Male gametes
Female gametes
Xw+
Xw+
Xw+Xw+
Y
Xw+Y
Red, female Red, male
Xw+Xw
XwY
Xw
Red, female White, male
If the gene is X-linked expect different ratios than if it was autosomal
All white-eyed flies should be male
All females should be red-eyed
3:1 ratio of red-eyed to white-eyed flies
32
• However
– The experimental ratio of red eyes to white eyes in
the F2 generation is (2,459 + 1,011):782 or about a
4.4:1 ratio instead of 3:1 ratio
– How can the lower-than-expected number of whiteeyed flies be explained?
• Decreased survival of white-eyed flies
33
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
• Sex linked traits can be confirmed by test crosses
– Testcross – a phenotypically dominant individual is
mated with recessive individual
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Testcross:
Male is XwY
F1 female is Xw+Xw
Male gametes
Female gametes
Xw
Xw+
Xw+Xw
Y
Xw+Y
Red, female Red, male
XwXw
XwY
Xw
White, female White, male
34
• Note in Morgan’s experiment:
– The observed data of the testcross are 129:132:88:86
– This ~ 1.5:1.5:1:1 ratio deviates from the predicted
1:1:1:1 ratio
– Again, lower-than-expected number of white-eyed flies
can be explained by a lower survival rate for those flies
35
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Pedigrees Can Identify X-linked Genes
• Example: Duchenne muscular dystrophy (DMD)
– Seen in both dogs and humans
– Gene for DMD is on the X chromosome
• Encodes dystrophin protein, needed for muscle structure
• Damages heart and breathing muscles
• Survival is rare beyond the early 30s
– X-linked recessive pattern
– Disease is rare in females; they may be carriers
– Carrier mothers have ~50% affected sons
• Refer to figure 4.10
36
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Pedigree of family with DMD
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Affected
with DMD
II-1
III-1
III-2
IV-1
IV-2
I-1
I-2
II-2 II-3
II-4
III-3
IV-3
III-4
IV-4
Unaffected,
presumed heterozygote
II-5
III-5
IV-5
II-6
III-6 III-7 III-8
IV-6
IV-7
37
Reciprocal Crosses
• Reciprocal cross – two crosses that differ in which sex
carries the trait
• Example: Duchenne muscular dystrophy (DMD)
– Reciprocal crosses demonstrate that it is X-linked in
dogs as well
– X-linked genes behave differently in reciprocal
crosses
• Refer to figure 4.11
38
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Reciprocal cross
XDXD
XdY
XdXd
Sperm
Xd
XDY
Sperm
XD
Y
XD
XDXd
(unaffected,
carrier)
XDY
(unaffected)
XD
XDXd
(unaffected,
carrier)
XDY
(unaffected)
Y
Xd
XdY
XDXd
(affected
(unaffected, with muscular
carrier)
dystrophy)
Xd
XdY
(affected
(unaffected, with muscular
carrier)
dystrophy)
XDXd
© AP Images.
(a) Male golden retriever with
X-linked muscular dystrophy
(b) Examples of X-linked muscular
dystrophy inheritance patterns
Figure 4.11
39