Transcript Foundations of Biology - Geoscience Research Institute

Matthew 18:11
11 For the Son of man is
come to save that
which was lost.
©2000 Timothy G. Standish
Chromosomal Basis
of Inheritance
Timothy G. Standish, Ph. D.
©2000 Timothy G. Standish
Introduction- Gregor Mendel
 Father
of classical genetics.
 Born 1822 to peasant family in the
Czech village of Heinzendorf, part of
the Austro-Hungarian empire at the
time.
 Austrian Augustinian monk (Actually
from Brunn which is now in the Czech
Republic).
©2000 Timothy G. Standish
Gregor Mendel - Education
 Studied
mathematics in Olmutz
college.
 Attended University of Vienna 1851 1853. Influenced by:
– Franz Unger, a plant physiologist who
believed new species could come about
via hybridization.
– Christian Doppler, physicist who
discovered the Doppler effect.
Sharpened his math skills.
©2000 Timothy G. Standish
Gregor Mendel - Work
 Studied
peas which he grew in a garden
outside of the Abbey where he lived
starting 1856 (3 years prior to
publication of Origin of Species).
 Showed that the traits he studied
behaved in a precise mathematical way
and disproved the theory of "blended
inheritance."
©2000 Timothy G. Standish
Gregor Mendel - Work Cont.
 Published
rules of transmission of
genes in 1866 (handwritten in German,
not Latin!). Work was totally ignored.
 Mendel’s work was rediscovered in
1900 by three botanists:
– Carl Correns (Germany)
– Erich von Tschermak (Austria)
– Hugo de Vries (Holland)
©2000 Timothy G. Standish
3 Reasons Mendel’s Work
Was Ignored
Mendel
was not on the ball
Biologists didn’t know
mathematics
Lack of independent
supporting discoveries
©2000 Timothy G. Standish
Reasons Mendel’s
Work Was Ignored:
1) Mendel was not on the ball
 Wrote
in an obscure journal
(Proceedings of the Natural History
Society of Brunn).
 Wrote in German, not Latin.
 Mendel was not well known and did not
persevere in his attempt to push his
ideas.
©2000 Timothy G. Standish
Reasons Mendel’s
Work Was Ignored:
2) Biologists didn’t know math
 Biologists
didn’t understand math very
well.
 Biologists were interested in the
explaining the transmission of continuous
traits like height, esp. after publication of
Origin of Species in 1859. Mendel
suggested that inherited characteristics
were discrete units (discontinuous).
©2000 Timothy G. Standish
Reasons Mendel’s
Work Was Ignored:
3) Lack of independent supporting
discoveries:
 There
was no physical element in which
Mendel’s inherited particles could be
identified.
 By the turn of the century, chromosomes
had been discovered (physical particles)
and biologists were better at math.
©2000 Timothy G. Standish
Chromosomes:
The Physical Basis of Inheritance
 1866
Mendel published his work
 1875 Mitosis was first described
 1890s Meiosis was described
 1900 Mendel's work was rediscovered
 1902 Walter Sutton, Theodore Boveri
and others noted parallels between
behavior of chromosomes and alleles.
©2000 Timothy G. Standish
Chromosomal Theory
of Inheritance
 Genes
have specific loci on
chromosomes.
 Chromosomes undergo segregation
(meiosis) and independent
assortment,
 Thus alleles of genes are
independently assorted.
©2000 Timothy G. Standish
Chromosomal Theory
of Inheritance Telophase I
E
Prophase I
Crossing Over
e
Replication
E
n
E e
n N
E
e
n
N
e
n
N
e
E
e
n
N
N
n
e
N
E
N
E
e
E
n
Telophase II
N
n
©2000 Timothy G. Standish
Independent Assortment
Eggs
As long as genes are on
different chromosomes,
they will assort
independently
Sperm
EN En
eN
en
EN
EENN
EENn
EeNN
EeNn
En
EENn
EEnn
EeNn
Eenn
eN
EeNN
EeNn
eeNN
eeNn
en
EeNn
Eenn
eeNn
eenn
©2000 Timothy G. Standish
Two Genes On One
Chromosome Telophase I
Prophase I
Replication
E
E
e
e
e
E
e
A
A
E
a
A
a
a
A
E e
A A
a a
Telophase II
a
As long as genes on the same
chromosome are located a long
distance apart, they will assort
independently due to crossing
over during Prophase I of
meiosis
E e
E
e
E
e
A
A
a
a
©2000 Timothy G. Standish
 First
Thomas Hunt Morgan
to associate a trait (gene) with a
chromosome.
 Worked with fruit flies (Drosophila
melanogaster)
 Why fruit flies?
– Short generation time (≈ 2 weeks)
– Survive and breed well in the lab
– Very large chromosomes in some cells
– Many aspects of phenotype are genetically
controlled.
©2000 Timothy G. Standish
Drosophila Nomenclature
+
= Wild type, phenotype in nature (i.e., red
eyes and round wings)
 Mutants are alternatives to the wild type
 Fruit fly genes are named after the mutant
 Dominant mutations are capitalized (i.e.,
Hairless or H and Bar or B)
 Recessive mutants are named using lower
case letters (i.e., black or b and white or w)
©2000 Timothy G. Standish
Drosophila Mutations
©2000 Timothy G. Standish
More Drosophila Mutations
Wild Type ++
ebony body ee
white eyes ww
©2000 Timothy G. Standish
Sex Determination
 Two
ways in which sex can be determined:
 Environment:
 Turtles
- Temperature of development
 Some fish - Social structure
 Chromosomes
- Three methods:
 XO
- Haploid/diploid, i.e., bees, haploid males
diploid females
 ZW - Heterogametic (ZW) females, homogametic
(ZZ) males, i.e., birds
 XY - Heterogametic (XY) males, homogametic
(XX) females, i.e., humans and Drosophila
©2000 Timothy G. Standish
X-Chromosome Human and
Drosophila Genes Are Easy To Find
 In
humans and Drosophila, males are
XY
 Thus males are haploid for the X
chromosome
 Because of this, recessive genes on the
X chromosome show up far more
commonly in male than female
phenotypes
©2000 Timothy G. Standish
Morgan’s Discovery Of An XLinked Drosophila Gene
X+ X+
A white-eyed
male was
discovered
P
X
1/4
Xw X+ Xw X+
Y
X+Y X+Y
F1
X
1/4
Xw
1/2
X+ Xw
X+
X+ X+ Xw X+
Y
X+Y XwY
F2
©2000 Timothy G. Standish
The Key To Morgan’s Discovery
The key to Morgan’s discovery was the
observation that all the white-eyed individuals in
the F2 generation were males
 Without this vital data on the association of white
eyes with being male, the gene for white eyes
could have been seen as a simple recessive trait on
an autosome
 This illustrates the importance of recording all the
data possible and being alert to the possibility of
interesting things being present in the data
 “Fate favors the prepared mind” (Louis Pasteur)

©2000 Timothy G. Standish
Human X-linked Recessive
Genes
 Brown
enamel - Tooth enamel appears
brown rather than white
 Hemophilia - Two types:
– A - Classic hemophilia, deficiency of
blood-clotting factor VIII
– B - Christmas disease, deficiency of
blood-clotting factor IX
©2000 Timothy G. Standish
X-linked Recessive Genes
Related to Sight
 Coloboma
iridis - A fissure in the eye’s iris
 Color Blindness - Two types:
– Deutan - Decreased sensitivity to green light
– Protan - Decreased sensitivity to red light
 Congenital
night blindness - Not due to a
deficiency of vitimin A
 Microphthalmia - Eyes fail to develop
 Optic atrophy - Degeneration of the optic
nerves
©2000 Timothy G. Standish
Variation In Chromosome
Number - Polyploidy


Polyploid individuals have more than two sets of
chromosomes
Many important commercial plants are polyploid:
– Roses
– Navel oranges
– Seedless watermelons

Polyploid individuals usually result from some sort of
interruption during meiosis
1n Gamete
+
Interruption
of meiosis
Pro or Metaphase I Metaphase II
2n
Gametes
3n Zygote
©2000 Timothy G. Standish
Variation In Chromosome
Number - Aneuploidy



Polyploid humans are unknown, but individuals with extra
individual chromosomes are known.
Having extra chromosomes or lacking some chromosomes
is called aneuploidy
Aneuploid individuals result from nondisjunction during
meiosis
+
Zygote
Metaphase I
Anaphase I
+
Zygote
©2000 Timothy G. Standish
Aneuploidy In Humans








Most human aneuploids spontaneously abort
The most viable variations in chromosome number are
those that deal with the sex chromosomes:
XO - Turner’s Syndrome - Phenotypically females
XXX…- “Super” females
XYY… - “Super” Males - On average tend to be larger and
less intelligent
XXY - Klinefelter’s Syndrome - Phenotypically male
Of the non-sex chromosome aneuploids, Down’s
Syndrome, extra chromosome 21, tends to be the most
viable
Down’s Syndrome is more common in children of mothers
who gave birth after age 40
©2000 Timothy G. Standish
Gene Dosage
 There
seem to be elegant mechanisms
for maintaining the correct dosage of
genetic material in each cell
 When aneuploidy causes a change in the
relative dose of one chromosome,
problems result
 Another way in which dosage of genetic
material can be changed is via
macromutations
©2000 Timothy G. Standish
Macromutations
 Four
major types of Macromutations are
recognized:
1 Deletions - Loss of chromosome sections
2 Duplications - Duplication of chromosome
sections
3 Inversions - Flipping of parts of
chromosomes
4 Translocations - Movement of one part of a
chromosome to another part
©2000 Timothy G. Standish
Macromutation - Deletion
Chromosome
Centromere
Genes
A
B
C
D
E
F
A
B
C
D
G
H
G
H
E
F
©2000 Timothy G. Standish
Macromutation - Duplication
Chromosome
Centromere
Genes
A
B
C
D
E
F
G
H
A
B
C
D
E
F
EE
FF
G
H
Duplication
©2000 Timothy G. Standish
Macromutation - Inversion
Chromosome
Centromere
Genes
A
B
C
D
E
F
A
B
C
D
F
E
Inversion
G
H
G
H
©2000 Timothy G. Standish
Macromutation - Translocation
Chromosome
Centromere
A
B
C
A
B
E
Genes
D
F
E
C
F
G
H
D
G
H
©2000 Timothy G. Standish
The Lyon Hypothesis
Having extra chromosomes causes problems (e.g.,
Down’s Syndrome)
 Men have only one X chromosome and they are
normal (at least they think so)
 Women have two X chromosomes and they are
normal
 Mary Lyon proposed that the extra dosage of X
chromosome that women have is compensated for
by turning off one of the X chromosomes.
 This turned-off chromosome can be observed as a
“Barr Body” in metaphase female nuclei

©2000 Timothy G. Standish
Consequences of X-Chromosome
Dosage Compensation
 During
early development, X chromosomes
are randomly turned off in female cells
 All daughter cells have the same X
chromosome inactivated as their parental
cell.
 Thus, females are a mosaic of patches of
cells, some patches expressing the genes on
the paternal X chromosome, other patches
expressing the maternal X chromosome
©2000 Timothy G. Standish
Consequences of X-Chromosome
Dosage Compensation
XX
Zygote
XX
XX
At some point (probably later than the 4-cell
stage) half the X chromosomes are turned off
Daughter cells inherit the mother cell’s
XX XX
mixture of off and on X chromosomes
XX
Cell division
Because of dosage
compensation, females are
thought to be a mosaic of
patches of cells with each
patch expressing the same
X chromosome, but none
expressing both
chromosomes
XX
Different patches of cells
inherit different act X
chromosomes
©2000 Timothy G. Standish
 Orange
Why Calico Cats
Are Usually Female
coat color is a sex-linked trait in
cats (it is on the X chromosome)
 A female cat heterozygous for orange,
has skin patches expressing the orange X
with the other X chromosome turned off.
In other patches the opposite occurs.
©2000 Timothy G. Standish
Problem 1
In Drosophila, vermilion (v) is recessive to red (v+)
eyes and miniature (m) wings are recessive to normal
(m+) wings. The following cross was made:
Male v+v+m+m+ x vvmm Female
A What was the phenotype of the F1 generation?
B What F2 phenotypic ratio would you expect?
C If the actual F2 phenotypic numbers were:
– 147 red-eyed normal winged
– 49 vermilion-eyed miniature winged,
– 2 red-eyed miniature winged,
– 2 vermilion-eyed normal winged,
How would you explain this?

©2000 Timothy G. Standish
Solution 1
A What was the phenotype of the F1 generation?
v+v+m+m+ makes v+m+ gametes
vvmm makes vm gametes
Thus the F1 must be v+vm+m
B What F2 phenotypic ratio would you expect?
9 red-eyed normal winged (v+_m+_)
3 red-eyed miniature winged (v+_mm)
3 vermilion-eyed normal winged (vvm+_)
1 vermilion-eyed miniature winged (vvmm)
©2000 Timothy G. Standish
Solution 1 Continued
C If the actual F2 phenotypic numbers were:
– 147 red-eyed normal winged
– 49 vermilion-eyed miniature winged,
– 2 red-eyed miniature winged,
– 2 vermilion-eyed normal winged,
How would you explain this?
v+
m+
v+
v
m
v
m
m+
v+
m+
v+
m
v
m+
0.01
0.01
v
m
0.49
0.49
F1 Gametes
©2000 Timothy G. Standish
Solution 1 Continued
v
+
v+
m+
v+
v
m
0.49
v+m+
0.49
v+m+
0.01
v +m
0.01
vm+
0.49
vm
v
0.01
v +m
0.01
vm+
m
m+
m+
0.49
v+
m
v
m+
0.01
0.01
v
m
0.49
0.49
vm
0.0049
0.2401
0.2401 v+0.0049
+
+
+
+
+
+
+
v+v+m+m+ v m m v vm m v vm m
0.74 v+_m+_
(0.74*200=148)
0.0049
0.0001
0.0001
+
+
+
+
+
v v m m v v mm v+vm+m
0.0049
v+vmm
0.01 v+_mm
(0.01*200=2)
0.0049
0.0001
0.0001
+
+
+
+
+
v vm m v vm m vvm+m+
0.0049
vvm+m
0.01 vvm+_
(0.01*200=2)
0.2401
v+vm+m
0.2401
vvmm
0.24 vvmm
(0.24*200=48)
0.0049
v+vmm
0.0049
vvm+m
©2000 Timothy G. Standish
Solution 1 Continued
v
m
1cM



Vermilion and miniature winged are closely linked
genes on the same chromosome
The distance between vermilion and miniature is 1
centimorgan
The reason numbers in the cross do not fit the
prediction of 1 centimorgan exactly is that the
numbers are the result of chance and thus would not
be expected to fit the predicted ratio perfectly
©2000 Timothy G. Standish
Problem 2

How is the gene tracked in the pedigree shown below
inherited? In other words, what is its mode of
inheritance?
Use deductive reasoning to
A.
Aa
aa
aa
Aa
A_
A_
A_
aa
aa
A_
?
A_
A_
solve this problem
Aa
A_
Aa
aa
Hypothesis 1 - Autosomal
dominant
Hypothesis 2 - Autosomal
recessive
Hypothesis 3 - Sex linked
dominant
Hypothesis 4 - Sex linked
recessive
Answer - Either sex linked recessive (most
likely) or autosomal recessive
aa
©2000 Timothy G. Standish
Problem 2

How is the gene tracked in the pedigree shown below
inherited? In other words, what is its mode of
inheritance?
B.
©2000 Timothy G. Standish
©2000 Timothy G. Standish