Download X w

Proof for the chromosome theory of
inheritance
Sex chromosomes
Although these were convincing correlations, actual proof of the
chromosome theory required the study of sex chromosomes.
Remember, Mendel had found that reciprocal crosses produce
equal results with respect to the progeny. In general geneticists
confirmed his results.
However exceptions arose. The most famous exception was that
discovered by Thomas Hunt Morgan in the fruit fly Drosophila
melanogaster. Drosophila eyes are normally bright red.
Morgan discovered a white-eyed male.
He performed the following crosses:
1
Morgans crosses
CROSS P1
White
Red
F1
Both males and females were Red
Red is dominant to white
Selfing
3:1 red:white
(1 gene for eye color)
All white eyed flies were male!!!!
F2
Reciprocal cross
CROSS P2
White
Red
F1
Red
F2:
White
1:1 Red:white
All females were red and males were white in the F1!!!
2
X and Y chromosomes
Somehow eye color was linked to sex
The key to understanding this pattern of inheritance arose from
work demonstrating that males and females of a given species
often differ in the chromosome constitution.
For example, they found that male and female Drosophila both
have four chromosome pairs. However in males one of the pairs
the members differed in size:
Female Drosophila:
Male Drosophila:
Sex
fourth
second
third
3
Sex chromosomes
Sex is a phenotype
Morgan realized that difference in chromosome composition was
the basis of sex differences in Drosophila:
Furthermore, females produce only X-bearing gametes, while
males produce X and Y-bearing gametes.
X
X
X
Y
XX
XY
XX
XY
2
:2
If the gene for eye color resides on a X chromosome
There is no counterpart for this gene on the Y chromosome
4
Morgans crosses
CROSS1
White
Red
Red
Selfing
3:1 red:white
All white eyed flies were male!!!!
5
Formal explanation
Females have 2 copies of the eye color gene and males have one copy
W (red) is dominant over w (white)
CROSS1
white
XwY
Red
XWXW
F1
Xw
XW
XW Xw
Red
y
XWY
Red
6
Formal explanation
Females have 2 copies of the eye color gene and males have one copy
W (red) is dominant over w (white)
Self cross
Red
XWY
Red
XWXw
F2
XW
XW
Xw
XW XW
y
XWY
Red
Red
XW Xw
XwY
Red
White
7
Morgans crosses
Reciprocal cross
CROSS2
White
Red
Red
White
All females were red and males were white in the F1!!!
8
Formal explanation
The reciprocal cross
Red
XWY
White
XwXw
F1
XW
Xw
XW Xw
Red
y
XwY
White
In the F1 all the females are red and all the males are white
9
Formal explanation
White
XwY
Red
XWXw
F2
Xw
XW
Xw
XW Xw
y
XWY
Red
Red
Xw Xw
XwY
White
50% Red and 50% white!!!
This is in effect a test cross
White
10
Equal numbers of male and female progeny are produced.
Morgan realized that he could explain the inheritance patterns of
eye color by assuming:
1.
The gene determining eye color resides on the X chromosome
(red and white eyes represent normal and mutant alleles of
this gene)
2. There is no counterpart for this gene on the Y chromosome
Thus females carry two copies of the gene, while males carry only a
single copy.
This is still Simply a Correlation!
Correlation does not equal causation!
11
Sex determination
Bridges a student of Morgan set up the cross outlined above in
large numbers
P cross:
white females
XwXw
x
x
red males
XWY
As expected, he obtained
red-eyed females (XwXW) and
white-eyed males (XwY)
BUT
About 1 in every 2500 progeny he obtained white-eyed fertile
female or a red-eyed sterile male
Cherish Your Exceptions
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Primary exception
About 1 in every 2500 progeny he obtained a white-eyed fertile
female or a red-eyed sterile male.
These were called primary exceptional progeny
How can these exceptional progeny be explained?
disjunction
Non-disjunction
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Primary exception
About 1 in every 2500 progeny he obtained a white-eyed fertile
female or a red-eyed sterile male.
These were called primary exceptional progeny
How can these exceptional progeny be explained?
autosome
X
autosome
X
disjunction
Non-disjunction
Bridges suggested that occasionally during meiosis the X
chromosomes fail to separate.
ｷ
Normal separation of the X chromosomes
produces Xw gametes
ｷ
Failure of X chromosome separation
(non disjunction) Creates XwXw and nullo gametes and
these gametes give rise to the sterile red eyed
males!
14
Bridges and non-dysjunction
white
red
XWY
XwXw
F1
XW
Xw
Xw
Xw Xw
O
y
XW Xw
XwY
Red
white
XW Xw
XwY
Red
White
XW Xw Xw
Xw XwY
Lethal
white female
fertile
XW
Red male
Sterile
Y
Lethal
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Bridges assumed that XXX and Y0 progeny die
The only two viable progeny types were XXY and X0
In this model sex is determined by the number of X
chromosomes rather than the presence or absence of the Y
chromosome
This model makes a strong prediction -Hypothesis
Genes reside on chromosome
The exceptional red-eyed males should be X0
and
The exceptional white eyed females should be XXY
How do you show this?
16
Look at the chromosomes under the microscope
THAT IS WHAT BRIDGES SAW under the microscope in
the white females!
17
Non-Dysjunction in Meiosis I
XaXA
x
XaY
Replication
XaXaXAXA
x
XaXaYY
Non Dysjunction in
Non Dysjunction in
meiosisI in mother
meiosis I in father
XaXaXAXA and O
XaXaYY and O
Normal meiosis II
XaXA
and
O
XaY
and
O
Non Dysjunction in meiosis II
XaXA
x
XaXaXAXA
Replication
x
Normal meiosisI in mom
XaXa and
XAXA
XaY
XaXaYY
Normal meiosis I in dad
XaXa
and
YY
Non Dysjunction in meiosis II
XaXa or XAXA & nullo
XaXa or YY &
nullo
Aneuploid: Having a chromosome number that is not a multiple of 1
the haploid number for the species
Answer-- Triploids
What classes of progeny would be expected if you could do the
following cross
White
XwXwY
XW
XwXw
Y
Xw
XwY
XW XwXw
lethal
XWY
Red male
XW Xw
red
XWY
Y
Y XwXw
white female
YY
lethal
Y Xw
Red female
White male
XW XwY
Y XwY
Red female
Normal females are red eyed
Normal males are white eyed
Non-disjunct females are white eyed
Non-disjunct males are red eyed
White male
20
Sex in organisms
Sex chromosomes and sex:
In Drosophila, it is the number of X's that determine sex while
in mammals it is the presence or absence of a Y chromosome
that determines sex.
Homogametic sex- Producing gametes that contain one type of
chromosome (females in mammals and insects, males in birds and
reptiles)
Heterogametic sex- Producing gametes that contain two types
of chromosomes (males in mammals and insects, females in birds
and reptiles)
Species
XX
XY
XXY
XO
Drosophila
Female
male
female
male
Human
Female
male
male
female
Non-sex chromosomes are called autosomes
Humans have 22 autosomes, Drosophila has 3
Hemizygous
Gene present in one copy in a diploid organism
Human males are hemizygous for genes on the X-chromosome
21
Karyotype
Bridges confirmed aneuploidy by visualizing abnormal
chromosome numbers in Drosophila using the microscope.
Karyotype gives species specific chromosome organization
Description of length, number, morphology of all
Chromosomes
Karyotype analysis is extremely important in medicine.
Cheap and quick way to detect chromosome loss and large
alterations in chromosomes
Centromere
Alternations in karyotypes are linked to birth defects and
many human cancers.
Chromosome arms
Telomere
Unstained chromosome
Stained chromosome
22
Chromosome characteristics
Count Number of chromosomes/chromosome pairs
Centromere
Analyze chromosome arms by inspecting banding patterns
Chromosome arms
Telomere
Unstained chromosome
Stained chromosome
23
Chromosome number/size (haploid)
Organism
Yeast (S. cerevisiae)
Mold (Dictyostelium)
Arbidopsis
Lily
Nematode (C. elegans)
Fly (Drosophila)
Mouse
Human
number
16
7
5
12
6
4
20
23
Evolutionary significance of variability in number is not known
Human Chromosome Size
Ch #
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
X
Y
Chromosome size
246.1
243.6
199.3
191.7
181.0
170.9
158.5
146.3
136.3
135.0
134.4
132.0
113.0
105.3
100.2
90.0
81.8
76.1
63.8
63.7
46.9
49.3
153.6
22.7
Chromosomes vary in size
24
Morphology of chromosomes - Banding
Chromosomes can be stained
Cells in metaphase can be fixed and stained with dyes.
Dyes stain chromosomes and each chromosome has a
characteristic banding pattern.
In a diploid, homologous chromosomes have the same banding
pattern.
Stained chromosomes are photographed, cut and arranged in
decreasing size
Telocentric
Acrocentric
Metacentric
Position of
centromere on 25
each
chromosome
Karyotype
•
The human karyogram. The chromosomes are shown with the Gbanding pattern obtained after Giemsa staining. Chromosome
numbers and band numbers
Downs Syndrome
Staining and specific banding pattern allows you to line up and
identify various chromosomes
Down's syndrome results from an individual possessing three
copies of chromosome 21 rather than the normal two. It is the
most common of all human defects and occurs in 1/200
conceptions and 1/900 births.
Females over 35 years- segregation defect leading to three
copies of chromosome 21
Karyotype analyses of fetus indicates whether the child has
Downs.
Trisomies occur with other chromosomes as well but usually lead
to the death of the fetus
Normal female
Downs Male
XXY and XYY individuals are also found.
27
Aneuploidy is only seen for chromosomes 13, 18, 21 and X/Y in
humans
Karyotyping
Karyotyping provides a rapid means to identify alterations in the
number of chromosomes
Chromosome 21
In humans a very large number of conceptions are aneuploid
Over 70% of spontaneous miscarriages and early embryonic deaths
are caused due to Aneuploidy
~5-7% of early childhood deaths are due to aneuploidy
Humans have a rate of aneuploidy that is 10 times greater than
other mammals!
Non-dysjunction in meiosisI is the primary cause
In an individual
Monosomy = one chromosome of a pair is missing
Trisomy = extra chromosome is present
Chromosome 21 trisomies survive to adulthood
Downs syndrome occurs in 1 in 200 conceptions and
1 in 900 live births.
Turner syndrome (only full monosomy disease)
28
A
Aneuploidy-Monosomy/Trisomy
A
a
A
a
A
A
a
A
A
a
A
Non-dysjunction
In MeiosisI
a
a
a
A
A
A
A
A
a
a
a
A
A
a
Non-dysjunct
In MeiosisII
a
a
a
29
Triploidy
Species that are triploid, reproduce asexually (plant species)
What are the consequences of triploidy during mitosis and
meiosis?
Haploid
Diploid
Triploid
Mitosis in triploid
30
Meiosis and triploids
MeiosisI
Meiosis I
Triploids produce
unbalanced gametes
This is for one chromosome. If there are n chromosomes in an
organism, then balanced gametes (equal copies of all
chromosomes) is very rare.
31
What happens when you cross a triploid plant to a triploid plant?
4N
3N
3N
2N
32