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Chapter 15
The Chromosomal Basis of
Inheritance
What you learned already
•
Chapter 13 : Meiosis and sexual life cycles
•
Chapter 14 : Mendel and the gene idea
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Overview: Locating Genes on Chromosomes
☞Genes ( passengers) and chromosomes ( wagon)
•
Mendel’s “hereditary factors” were genes, though this wasn’t known at the time
•
Today we can show that genes are located on chromosomes
•
Q: How to visualize that?
•
The location of a particular gene can be seen by tagging isolated chromosomes
with a fluorescent dye that highlights the gene
 Chromosomes: a physical basis for the
principles of heredity (=Mendel’s laws
of segregation and independent
assortment)

This chapter’s aim:
Is to study the chromosomal basis
for the transmission of genes from
parents to offspring
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Concept 15.1: Mendelian inheritance has its
physical basis in the behavior of chromosomes
•
Mitosis and meiosis were first described in the late 1800s
•
The chromosome theory of inheritance states:
– Mendelian genes have specific loci (positions) on chromosomes
– Chromosomes undergo segregation and independent assortment
•
The behavior of chromosomes during meiosis can account for Mendel’s laws
of segregation and independent assortment
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 15.2
P Generation
Yellow-round
seeds (YYRR)
Y
ry

R R
Y
Green-wrinkled
seeds (yyrr)
r
y
Meiosis
Fertilization
y
R Y
Gametes
r
All F1 plants produce
yellow-round seeds (YyRr).
F1 Generation
R
y
r
Y
R
r
y
Y
Meiosis
LAW OF SEGREGATION
The two alleles for each
gene separate during
gamete formation.
r
R
Y
y
r
R
LAW OF INDEPENDENT
ASSORTMENT Alleles of genes
on nonhomologous chromosomes
assort independently during
gamete formation.
Metaphase I
Y
y
1
1
R
r
R
Y
y
r
Anaphase I
Y
y
R
r
Y
y
r
R
Y
y
2
2
Gametes
Y
Y
R
R
1/
F2 Generation
3
Metaphase II
y
r
4 YR
Fertilization recombines
the R and r alleles at
random.
1/
4
Y
Y
y
r
r
r
1/
yr
4
R
3
:3
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
:3
:1
R
1/
Yr
An F1  F1 cross-fertilization
9
y
y
4
yR
Fertilization results in the
9:3:3:1 phenotypic ratio
in the F2 generation.
Figure 15.2b
All F1 plants produce
yellow-round seeds (YyRr).
F1 Generation
R
R
y
r
y
r
Y
Y
LAW OF INDEPENDENT
ASSORTMENT Alleles of
genes on nonhomologous
chromosomes assort
independently during gamete
formation.
Meiosis
LAW OF SEGREGATION
The two alleles for each
gene separate during
gamete formation.
r
R
Y
y
r
R
Metaphase I
y
Y
1
1
R
r
r
R
Y
y
Anaphase I
Y
y
r
R
2
y
Y
Y
R
R
1/
4 YR
r
1/
4
y
Y
yr
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Y
Y
y
r
R
2
y
Y
Gametes
r
Metaphase
II
r
r
1/
4
Yr
y
y
R
R
1/
4
yR
Figure 15.2c
LAW OF INDEPENDENT
ASSORTMENT
LAW OF SEGREGATION
F2 Generation
3
Fertilization
recombines the
R and r alleles
at random.
An F1  F1 cross-fertilization
9
:3
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
:3
:1
3 Fertilization results
in the 9:3:3:1
phenotypic ratio in
the F2 generation.
Summary for the chromosomal basis of Mendel’s laws
•
Law of segregation:
•
Two alleles for each gene segregate during gamete formation and end
up in different gametes
•
 Each gamete gets only one of the two alleles
•
 In terms of chromosomes, this segregation corresponds to the
distribution of homologous chromosomes to different gamete (R or r
allele; Y or y allele)
•
Law of independent assortment:
•
Alleles of genes on nonhomologous chromosomes assort
independently during gamete formation
•
 Each gamete gets one of four allele combinations (YR:Yr:yR:yr =
1:1:1:1) depending on the alternative arrangements of homologous
chromosome pairs in metaphase I
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Morgan’s Experimental Evidence for chromosomal
theory: Scientific Inquiry
•
Thomas Hunt Morgan (Embryologist at Columbia Univ. early in the 20th
century)
–
Provided the first solid evidence associating a specific gene with a
specific chromosome
–
Namely, provided convincing evidence that chromosomes
are the location of Mendel’s heritable factors
Morgan’s Choice of Experimental Organism
•
Several characteristics make fruit flies a convenient organism for genetic
studies:
–
They breed at a high rate
–
A generation can be bred every two weeks
–
They have only four pairs of chromosomes
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
•
Morgan first observed and
noted : Wild type, or normal,
phenotypes that were common
in the fly populations
•
Traits alternative to the wild
type: Are called mutant
phenotypes
•
Morgan first invented a notation
for symbolizing alleles in
Drosophila (still widely used)
–
The allele for white eyes in
flies is symbolized by w
(indicated as a mutant allele)
–
A superscript + identifies the
allele for the wild-type trait:
w+ for the allele for red eyes
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
How to Correlate Behavior of a Gene’s Alleles with
Behavior of a Chromosome Pair
•
In one experiment, Morgan
mated male flies with white
eyes (mutant) with female flies
with red eyes (wild type)
– The F1 generation all had
red eyes
– The F2 generation
showed the 3:1 red:white
eye ratio, but only males
had white eyes
•
Morgan determined that the
white-eyed mutant allele must
be located on the X
chromosome
•
Morgan’s finding supported the
chromosome theory of
inheritance
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
•
Morgan’s discovery
that transmission of
the X chromosome in
fruit flies correlates
with inheritance of the
eye-color trait
–
Was the first
solid evidence
indicating that a
specific gene is
associated with
a specific
chromosome
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
성염색체 연관 유전자의 유전현상의 특징
• Concept 15.2: Sex-linked genes exhibit
unique patterns of inheritance
What will you examine here
 We consider the role of sex chromosome in heritance
 First step: reviewing the chromosomal basis of sex determination
in humans and some other animals
The Chromosomal Basis of Sex (성결정과 염색체)
How to determine sex in an organism?
•
An organism’s sex
–
Is an inherited phenotypic character determined by the presence
or absence of certain chromosomes (sex chromosomes)
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
•
In humans and other mammals,
there are two varieties of sex
chromosomes: a larger X
chromosome and a smaller Y
chromosome
•
Only the ends of the Y
chromosome have regions that
are homologous with the X
chromosome
•
The SRY gene on the Y
chromosome codes for the
development of testes
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Different systems of sex determination
– Are found in other organisms
22 +
XX
22 +
X
In grasshoppers, cockroaches, there is
only one type of sex chromosome (the
X)
76 +
ZZ
In birds, some fishes, and some
insects, the sex chromosome present
in the egg (not the sperm) determines
the sex of offspring (Z and W)
(b) The X–0 system
76 +
ZW
(c) The Z–W system
32
16
16
(Diploid)
(Haploid)
(d) The haplo-diploid system
In most species of bees and ants, there are
no sex chromosomes. Female develop
from fertilized eggs and are thus diploid.
Males develop from unfertilized eggs and
haploid (no fathers)
Figure 15.6b–d
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Inheritance of Sex-Linked Genes
Key points to keep in mind
•
The sex chromosomes have genes for many characters unrelated to sex
•
A gene located on either sex chromosome is called a sex-linked gene
•
In humans, sex-linked usually refers to a gene on the larger X chromosome
Sex-linked trait by recessive allele on X chromosome
•
Female: has two X chromosomes
–
•
Homozygous recessive alleles : expression of phenotype
– Heterozygous: no expression of phenotype (called carrier)
Male: has only one X chromosome
–
You don’t use the terms homozygous and heterozygous: use
“hemizygous”
–
Any male receiving the recessive allele from his mother will express
the trait  far more males than females have sex-linked recessive
disorders (The freq. of sex-linked recessive disorders in male is
higher than that in female)
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
What kinds of X-lined disorders are found?
•
Some recessive alleles found on the X chromosome in humans cause
certain types of disorders
–
Color blindness:
–
Duchenne muscular dystrophy : 1/3500 males born in US;
progressive weakening of the muscles; the absence of a key
muscle protein called dystrophin
–
Hemophilia: shows delayed blood clotting due to the absence
of one or more of the proteins required for blood clotting; treated
with intravenous injections of the missing protein
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
•How do sex-lined recessive traits transmit to offspring?
XAXa
(a) A father with the disorder will transmit the mutant allele to all
daughters but to no sons. When the mother is a dominant
homozygote, the daughters will have the normal phenotype
but will be carriers of the mutation.
Figure 15.7a–c
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
•The transmission of sex-linked recessive traits
XaXA
(b) If a carrier female mates with a male of normal phenotype, there is a
50% chance that each daughter will be a carrier like her mother, and
a 50% chance that each son will have the disorder.
Figure 15.7a–c
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
•The transmission of sex-linked recessive traits
XaXa
(c) If a carrier mates with a male who has the disorder, there is a
50% chance that each child born to them will have the disorder,
regardless of sex. Daughters who do not have the disorder will be
carriers, where as males without the disorder will be completely free
of the recessive allele.
Figure 15.7a–c
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
X inactivation in Female Mammals
•
In mammalian females, one of
the two X chromosomes in
each cell is randomly
inactivated during embryonic
development
•
The inactive X condenses into
a Barr body
•
If a female is heterozygous for
a particular gene located on
the X chromosome, she will
be a mosaic for that
character
Mystery of the presence or absence of sweat glands in female skin
•
In humans, mosaicism can be observed in a recessive X-linked mutation that
prevents the development of sweat glands
•
A woman who is heterozygous for this trait has patches of normal skin and patches
of skin lacking sweat glands
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Concept 15.3: Linked genes tend to be
inherited together because they are located
near each other on the same chromosome
Each chromosome has hundreds or thousands of genes
Location of some genes on the same
chromosome is expected
The genes tend to be inherited
together in genetic crosses: are said
to be linked genes
The linked genes do not
always follow Mendel’s law
of independent assortment
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
How Linkage Affects Inheritance
•
Morgan did other
experiments with
fruit flies to see
how linkage
affects
inheritance of two
characters
•
Morgan crossed
flies that differed
in traits of body
color and wing
size
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
•
However, nonparental phenotypes
were also produced
•
The production of a small
number of offspring with
nonparental phenotypes
indicated that some mechanism
occasionally breaks the linkage
between genes on the same
chromosome
•
Understanding this result involves
exploring genetic recombination,
the production of offspring with
combinations of traits differing from
either parent
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Genetic Recombination and Linkage
What you learned in the Chapter 13
Meiosis and random fertilization generate genetic variation among
offspring of sexually reproducing organisms
•
The genetic findings of Mendel and Morgan relate to the
chromosomal basis of recombination
What will you examine next
What is the chromosomal basis of recombination in relation
to the genetic findings of Mendel and Morgan?
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Recombination of Unlinked Genes: Independent
Assortment of Chromosomes
•
Mendel observed that
combinations of traits in some
offspring differ from either
parent
•
Offspring with a phenotype
matching one of the parental
phenotypes are called
parental types
•
Offspring with nonparental
phenotypes (new combinations
of traits) are called
recombinant types, or
recombinants
•
A 50% frequency of
recombination is observed for
any two genes on different
chromosomes
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Recombination of Linked Genes: Crossing Over
•
Morgan discovered that genes can be linked, but the linkage was
incomplete, because some recombinant phenotypes were observed
•
He proposed that some process must occasionally break the
physical connection between genes on the same chromosome
•
That mechanism was the crossing over of homologous
chromosomes
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 15.10
Black body, vestigial wings
(double mutant)
Gray body, normal wings
(F1 dihybrid)
Testcross
parents
Chromosomal basis
for recombination
of linked genes:
Linked genes
exhibit RF less
than 50%
b vg
b vg
b vg
b vg
Replication
of chromosomes
Meiosis I
Replication
of chromosomes
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
Meiosis I and II
b vg
b vg
b vg
Meiosis II
Recombinant
chromosomes
bvg
b vg
b vg
b vg
Eggs
Testcross
offspring
965
Wild type
(gray-normal)
944
Blackvestigial
206
Grayvestigial
185
Blacknormal
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
Parental-type offspring
Recombinant offspring
391 recombinants
Recombination

 100  17%
frequency
2,300 total offspring
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
b vg
Sperm
Figure 15.10a
Gray body, normal wings
(F1 dihybrid)
Testcross
parents
Black body, vestigial wings
(double mutant)
b vg
b vg
b vg
b vg
Replication
of chromosomes
Meiosis I: Crossing
over between b and vg
loci produces new allele
combinations.
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
Meiosis I and II:
Even if crossing over
occurs, no new allele
combinations are
produced.
b vg
b vg
Meiosis II: Segregation
of chromatids produces
recombinant gametes
with the new allele
combinations.
bvg
Replication
of chromosomes
b vg
Recombinant
chromosomes
b vg
b vg
Eggs
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
b vg
b vg
Sperm
Figure 15.10b
Recombinant
chromosomes
Eggs
Testcross
offspring
bvg
965
Wild type
(gray-normal)
b vg
944
Blackvestigial
206
Grayvestigial
b vg
185
Blacknormal
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
Parental-type offspring
RF: the percentage
of recombinants in
the total offspring
b vg
Recombinant offspring
Recombination
391 recombinants  100  17%

frequency
2,300 total offspring
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
b vg
Sperm
Mapping the Distance Between Genes Using
Recombination Data: Scientific Inquiry
•
Alfred Sturtevant, one of Morgan’s students, constructed a genetic map,
an ordered list of the genetic loci along a particular chromosome
•
Sturtevant predicted that the farther apart two genes are, the higher
the probability that a crossover will occur between them and
therefore the higher the recombination frequency
•
A linkage map is a genetic map of a chromosome based on
recombination frequencies
•
Distances between genes can be expressed as map units; one map unit,
or centimorgan, represents a 1% recombination frequency
•
Map units indicate relative distance and order, not precise locations of
genes
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
How to construct a linkage map
Example
 Consider three genes: the body-color (b), wing-size (vg), and cinnabar
eyes (cn) [brighter red than wt eye color]
 The observed recombination frequencies between three Drosophila
gene pairs : b–cn 9%, cn–vg 9.5%, and b–vg 17%
 Make a linear order : cn is positioned about halfway between the other
two genes:
RESULTS
Recombination
frequencies
9%
Chromosome
9.5%
17%
b
Figure 15.11
b, black body color
vg, vestigial wing
cn, cinnabar eyes
cn
1st cross-over
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
vg
2nd CO
How to construct a linkage map (continued)
Example
Inquiry: The b–vg recombination frequency (17%) is slightly less
than the sum (18.5%) of the b–cn and cn–vg frequencies. Why?
 Because double crossovers are fairly likely to occur between b
and vg in matings tracking these two genes.
 A second crossover would “cancel out” the effect of the first
crossover and thus reduce the observed b–vg RF.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Canceling out of the effect of the 1st crossover by 2nd cross-over
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
•
Genes that are far apart on the same chromosome can have a
recombination frequency near 50%
•
Such genes are physically linked, but genetically unlinked, and
behave as if found on different chromosomes
•
Sturtevant used recombination
frequencies to make linkage
maps of fruit fly genes
•
Using methods like
chromosomal banding,
geneticists can develop
cytogenetic maps of
chromosomes
•
Cytogenetic maps indicate the
positions of genes with respect
to chromosomal features
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Concept 15.4: Alterations of chromosome
number or structure cause some genetic
disorders
•
Large-scale chromosomal alterations in humans and other mammals
often lead to spontaneous abortions (miscarriages) or cause a variety
of developmental disorders
•
Plants tolerate such genetic changes better than animals do
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Abnormal Chromosome Number
•
In nondisjunction,
pairs of
homologous
chromosomes do
not separate
normally during
meiosis
•
As a result, one
gamete receives
two of the same
type of
chromosome, and
another gamete
receives no copy
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The consequences of nondisjunction after fertilization?
•
Aneuploidy
–
–
Results from the fertilization of
aberrant gametes (nondisjunction
occurred) with a normal one
Chromosome number of haploid (gamete): n
•
Chromosome number of normal zygote: 2n
•
If a zygote is trisomic (2n+1 chromosomes)
•
It has three copies of a particular
chromosome
If a zygote is monosomic (2n-1 chromosomes)
–
It has only one copy of a particular
chromosome
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Polyploidy is a condition in which
an organism has more than two
complete sets of chromosomes
– Triploidy (3n) is three sets of
chromosomes
Is a condition in which offspring
have an abnormal number of a
particular chromosome
•
–
•
– Tetraploidy (4n) is four sets
of chromosomes
•
Polyploidy is common in plants, but
not animals
•
Polyploids are more normal in
appearance than aneuploids
Alterations of Chromosome Structure
•
Breakage of a chromosome
can lead to four types of
changes in chromosome
structure
– Deletion removes a
chromosomal
segment
– Duplication repeats a
segment
– Inversion reverses
orientation of a
segment within a
chromosome
– Translocation moves
a segment from one
chromosome to
another
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Human Disorders Due to Chromosomal Alterations
•
Alterations of chromosome number and structure are associated with
some serious disorders
•
Some types of aneuploidy appear to upset the genetic balance less than
others, resulting in individuals surviving to birth and beyond
•
These surviving individuals have a set of symptoms, or syndrome,
characteristic of the type of aneuploidy
Down Syndrome (Trisomy 21)
•
Down syndrome is an aneuploid
condition that results from three
copies of chromosome 21
•
It affects about one out of every
700 children born in the United
States
•
The frequency of Down syndrome
increases with the age of the
mother, a correlation that has not
been explained
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Aneuploidy of Sex Chromosomes
•
Nondisjunction of sex chromosomes produces a variety of aneuploid
conditions
•
Klinefelter syndrome is the result of an extra chromosome in a male,
producing XXY individuals
•
Monosomy X, called Turner syndrome, produces X0 females, who are
sterile; it is the only known viable monosomy in humans
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Disorders Caused by Structurally Altered
Chromosomes
•
The syndrome cri du chat
(“cry of the cat”), results
from a specific deletion in
chromosome 5
•
A child born with this
syndrome is mentally
retarded and has a catlike
cry; individuals usually die
in infancy or early
childhood
•
Certain cancers, including
chronic myelogenous
leukemia (CML), are
caused by translocations of
chromosomes
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Concept 15.5: Some inheritance patterns are
exceptions to the standard chromosome theory
•
There are two normal exceptions to Mendelian genetics
•
One exception involves genes located in the nucleus, and the
other exception involves genes located outside the nucleus
•
In both cases, the sex of the parent contributing an allele is a
factor in the pattern of inheritance
Genomic Imprinting
•
For a few mammalian traits, the phenotype depends on which parent
passed along the alleles for those traits
•
Such variation in phenotype is called genomic imprinting (Monoallelic
expression)
•
Genomic imprinting involves the silencing of certain genes that are
“stamped” with an imprint during gamete production
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Genomic imprinting
Involves the silencing of certain genes that are
“stamped” with an imprint during gamete production
A zygote expresses only one allele of an imprinted
gene (either from the mother or the father)
 The imprints are transmitted to all the body cells
during development
A gene imprinted for maternal allele expression is
always imprinted for maternal allele expression,
generation to generation
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 15.17a
Genomic imprinting of the mouse Igf2 gene.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Inheritance of Organelle Genes
•
Extranuclear genes (or cytoplasmic
genes) are found in organelles in the
cytoplasm
•
Mitochondria, chloroplasts, and
other plant plastids carry small
circular DNA molecules
•
Extranuclear genes are inherited
maternally because the zygote’s
cytoplasm comes from the egg
•
The first evidence of extranuclear
genes came from studies on the
inheritance of yellow or white
patches on leaves of an otherwise
green plant (see next slide)
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings