Download Chromosomal Genetics

Exam II Lectures and Text Pages
• I. Cell Cycles
–
Mitosis (218 – 228)
–
Meiosis (238 – 249)
• II. Mendelian Genetics
• III. Chromosomal Genetics
• IV. Molecular Genetics
–
Replication
–
Transcription and Translation
• V. Microbial Models
• VI. DNA Technology
Chromosomal Genetics
• Genes are located on chromosomes
• Chromosomes can be visualized using various
techniques
Figure 15.1
Chromosomes: The Physical Basis of Mendelian Inheritance
• Several researchers proposed in the early
1900s that genes are located on chromosomes
• The behavior of chromosomes during meiosis
was said to account for Mendel’s laws of
segregation and independent assortment
1
CHROMOSOMAL GENETICS
• Discoveries in genetics and cytology
– 1860s: Mendel - discrete inherited factors
segregate and assort independently during
gamete formation
– 1875: Cytologists worked out mitosis
– 1890s: Cytologists worked out meiosis
– 1900: Several scientists independently
rediscovered Mendel's principles
Discoveries in Genetics and Cytology
• 1902: Sutton, Boveri, and others noted parallels in
the behavior of Mendel's factors (genes) and the
behavior of chromosomes
– both are paired in diploid cells
– Both homologous chromosomes and allele pairs
segregate during meiosis
– fertilization restores the paired condition for both
• From these observations, biologists deduced the
chromosomal basis of Mendel’s Laws
Chromosome Theory of Inheritance
P Generation
Yellow-round
seeds (YYRR)
Starting with two true-breeding pea plants,
we follow two genes through the F1 and F2
generations. The two genes specify seed
color (allele Y for yellow and allele y for
green) and seed shape (allele R for round
and allele r for wrinkled). These two genes are
on different chromosomes. (Peas have seven
chromosome pairs, but only two pairs are
illustrated here.)
Green-wrinkled
seeds (yyrr)
Y
R
Y
r
R
y
r
y
Meiosis
Fertilization
Genes are found on
chromosomes.
y
R Y
Gametes
r
All F1 plants produce
yellow-round seeds (YyRr)
R
R
y
F1 Generation
y
r
r
Y
Y
Meiosis
It is the chromosomes
that segregate and
independently assort
during gamete
formation.
LAW OF SEGREGATION
1 The R and r alleles segregate
at anaphase I, yielding
two types of daughter
cells for this locus.
R
Y
y
R
Y
y
LAW OF INDEPENDENT ASSORTMENT
1
y
R
r
y
r
R
Y
y
Alleles at both loci segregate
in anaphase I, yielding four
types of daughter cells
depending on the chromosome
arrangement at metaphase I.
Compare the arrangement of
the R and r alleles in the cells
on the left and right
r
R
Metaphase II
R
R
Y
Y
r
r
Y
r
r
1 yr
4
1 yr
4
2 Each gamete gets
a long and a short
chromosome in
one of four allele
combinations.
y
y
Y
Y
1
YR
4
3 Fertilization
recombines the
R and r alleles
at random.
r
r
F2 Generation
Figure 15.2
Two equally
probable
arrangements
of chromosomes
at metaphase I
Y
Y
Gametes
r
Anaphase I
Y
2 Each gamete
gets one long
chromosome
with either the
R or r allele.
R
y
y
R
R
1
yR
4
Fertilization among the F1 plants
9
:3
:3
:1
3 Fertilization results
in the 9:3:3:1
phenotypic ratio in
the F2 generation.
2
Morgan’s Experiments Support Chromosome Theory
• Thomas Hunt Morgan (early 1900’s)
– Provided convincing evidence that
chromosomes are the location of Mendel’s
heritable factors
– He traced a gene to a specific chromosome
Morgan’s Choice of Experimental Organism
• He chose Drosophila melanogaster because
they:
• a. Are easily cultured in the laboratory
• b. Are prolific breeders
• c. Have a short generation time
• d. Have only four pairs of chromosomes;
– autosomes (II, III, and IV); and sex
chromosomes (Females XX , males XY)
Wild Types vs. Mutants and Genetic Symbols
• 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’s genetic symbols are now
convention.
• A gene’s symbol is based on the first mutant
discovered.
– If the mutant is recessive: the first letter is
lowercase.
3
Correlating Behavior of a Gene’s Alleles with
Behavior of a Chromosome Pair
• Morgan discovered a single male fly with white
eyes. He mated this mutant white-eyed male
with a red-eyed (wild-type) female.
– The F1 generation all had
red eyes (wild-type is
dominant)
Figure 15.3
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Eye Color is Linked to Sex
– The F2 generation showed the 3:1 red:white
eye ratio, but only males (1/2) had white eyes
EXPERIMENT Morgan mated a wild-type (red-eyed) female
with a mutant white-eyed male. The F1 offspring all had red eyes.
• Morgan deduced
P
Generation
– That the whiteeye mutant
allele must be
located on the
X chromosome
X
F1
Generation
Morgan then bred an F1 red-eyed female to an F1 red-eyed male to
produce the F2 generation.
RESULTS The F generation showed a typical Mendelian
2
3:1 ratio of red eyes to white eyes. However, no females displayed the
white-eye trait; they all had red eyes. Half the males had white eyes,
and half had red eyes.
F2
Generation
Figure 15.4
White-Eye Allele is on the X
CONCLUSION Since all F offspring had red eyes, the mutant
1
white-eye trait (w) must be recessive to the wild-type red-eye trait (w+).
Since the recessive trait—white eyes—was expressed only in males in
the F2 generation, Morgan hypothesized that the eye-color gene is
located on the X chromosome and that there is no corresponding locus
on the Y chromosome, as diagrammed here.
P
Generation
W+
X
X
X
Y
W+
W+
W
W
Ova
(eggs)
F1
Generation
X
W+
Sperm
W+
W
Ova
(eggs)
F2
Generation
W+
W+
Sperm
W+
W+
W+
W
W
W
W+
4
Discovery of sex-linkage
• Females (XX) carry two copies of the gene,
males (XY) have only one.
– A mutant allele recessive, white-eyed female
must have that allele on both X chromosomes,
impossible for F2 females in the experiment.
– A white-eyed male has a single copy of the
mutant allele - confers white eyes.
• Sex-linked genes: Genes on sex
chromosomes. - commonly applied only to
genes on the X.
White-Eyes: Specific Gene on a Specific Chromosome
• 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
Linked Genes
• 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
5
How Linkage Affects Inheritance
• Morgan did other experiments with fruit flies
– To see how linkage affects the inheritance of
two different characters
Two Character (Dihybrid) Crosses
• Morgan crossed flies
– That differed in traits of two different
characters
P Generation
(homozygous)
EXPERIMENT
Morgan first mated true-breeding
Wild type
wild-type flies with black, vestigial-winged flies to produce
(gray body,
heterozygous F1 dihybrids, all of which are wild-type in
appearance. He then mated wild-type F1 dihybrid females with normal wings)
b+ b+ vg+ vg+
black, vestigial-winged males, producing 2,300 F2 offspring,
which he “scored” (classified according to
F1 dihybrid
phenotype).
Double mutant
(black body,
vestigial wings)
Double mutant
(black body,
vestigial wings)
x
b b vg vg
Double mutant
(black body,
vestigial wings)
b b vg vg
Double mutant
TESTCROSS
(wild type)
(black body,
x
(gray body,
vestigial wings)
normal wings)
CONCLUSION
If these two genes were on
different chromosomes, the alleles from the F1 dihybrid
would sort into gametes independently, and we would
expect to see equal numbers of the four types of offspring.
If these two genes were on the same chromosome,
we would expect each allele combination, B+ vg+ and b vg,
to stay together as gametes formed. In this case, only
offspring with parental phenotypes would be produced.
Since most offspring had a parental phenotype, Morgan
concluded that the genes for body color and wing size
are located on the same chromosome. However, the
production of a small number of offspring with
recombinant phenotypes indicated that some mechanism
occasionally breaks the linkage between genes on the
same chromosome.
b+ b vg+ vg
RESULTS
b vg
b+vg+
b vg
965
944
Wild type
Black(gray-normal) vestigial
b+ vg
b vg+
206
Grayvestigial
185
Blacknormal
Sperm
b+ b vg+ vg b b vg vg b+ b vg vgb b vg+ vg
Parental-type Recombinant (nonparental-type)
offspring
offspring
Figure 15.5
Autosomal Linkage
• Morgan determined that
– Genes that are close together on the same
chromosome are linked and do not assort
independently
– Unlinked genes are either on separate
chromosomes or are far apart on the same
chromosome and assort independently
b+ vg+
Parents
in testcross
Most
offspring
X
b vg
b vg
b vg
b+ vg+
b vg
or
b vg
b vg
6
Recombination of Unlinked Genes:
Independent Assortment of Chromosomes
• When Mendel followed the inheritance of two
characters
– He observed that some offspring have
combinations of traits that do not match either
parent in the P generation
Gametes from yellow-round
heterozygous parent (YyRr)
YR
Gametes from greenwrinkled homozygous
recessive parent (yyrr)
yr
Yr
yR
Yyrr
yyRr
yr
YyRr
yyrr
Parentaltype offspring
Recombinant
offspring
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Recombinant (non-parental) Offspring
• Recombinant offspring
– Are those that show new combinations of the
parental traits
• When 50% of all offspring are recombinants
– Geneticists say that there is a 50% frequency
of recombination
– This correlates to assortment between
unlinked genes
Recombination of Linked Genes: Crossing Over
• Morgan discovered that genes can be linked
– Sometimes the F2 offspring in a dihybrid
testcross do NOT occur in the 1:1:1:1
phenotypic ratio expected between unlinked
genes
– With complete linkage we expect to see only
two phenotypes (the parental types) in the F2
of a dihybrid testcross
– If we see any recombinant phenotypes in a
similar cross, then the linkage appears
incomplete
7
Crossing Over Breaks Linkage
• Morgan proposed that
– Some process must occasionally break the
physical connection between genes on the
same chromosome
– Crossing over of homologous chromosomes
was the mechanism
Linked Genes
– Exhibit recombination frequencies less than 50%
b+ vg+
Gray body,
normal wings
b vg
(F1 dihybrid)
Replication of
chromosomes
vg
b+
Testcross
parents
b vg
Black body,
vestigial wings
b vg (double mutant)
Replication of
chromosomes
b vg
×
b vg
vg
b+ vg+
vg
Meiosis I: Crossing
over between b and vg
loci produces new allele
combinations.
b
b
b vg
b vg
Meiosis II: Segregation
of chromatids produces
recombinant gametes
with the new allele
combinations.
Gametes
Meiosis I and II:
Even if crossing over
occurs, no new allele
combinations are
produced.
Recombinant
chromosome
Ova
Sperm
b+vg+
b vg
b+ vg
b vg+
b vg
b+ vg+
Testcross
offspring
Sperm
b vg
Figure 15.6
b vg
944
965
BlackWild type
(gray-normal) vestigial
b+ vg+
b vg+
b vg
b vg
b+ vg
206
Grayvestigial
b+ vg+
b vg
b vg+ Ova
185
Blacknormal Recombination
b vg+ frequency
=
391 recombinants
2,300 total offspring
×
100 = 17%
b vg
Parental-type offspring Recombinant offspring
Linkage Mapping: Using Recombination
Data
• A genetic map
– Is an ordered list of the genetic loci along a
particular chromosome
– Can be developed using recombination
frequencies
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
8
Some Genes Are Linked More Tightly Than Others.
• Alfred H. Sturtevant, Morgan's student
assumed: if crossing over occurs randomly,
the probability of crossing over between two
genes is directly proportional to the distance
between them.
– He used recombination frequencies to assign
genes a linear position on a chromosome
map
– He defined one map unit (centimorgan) as
1% recombination frequency.
A Linkage Map
•
Is the actual map of a chromosome based on recombination
frequencies
•
Sturtevant crossed flies using three characters (wing shape, body color
and eye color)
APPLICATION
A linkage map shows the relative locations of genes along a chromosome.
TECHNIQUE
A linkage map is based on the assumption that the probability of a crossover between two
genetic loci is proportional to the distance separating the loci. The recombination frequencies used to construct
a linkage map for a particular chromosome are obtained from experimental crosses, such as the cross depicted
in Figure 15.6. The distances between genes are expressed as map units (centimorgans), with one map unit
equivalent to a 1% recombination frequency. Genes are arranged on the chromosome in the order that best fits the data.
RESULTS In this example, the observed recombination frequencies between three Drosophila gene pairs
(b–cn 9%, cn–vg 9.5%, and b–vg 17%) best fit a linear order in which cn is positioned about halfway between
the other two genes:
Recombination
frequencies
9.5%
9%
17%
Chromosome b
cn
vg
The b–vg recombination frequency is slightly less than the sum of the b–cn and cn–vg frequencies because double
crossovers are fairly likely to occur between b and vg in matings tracking these two genes. A second crossover
Figure 15.7 would “cancel out” the first and thus reduce the observed b–vg recombination frequency.
Incomplete Linkage
• The farther apart genes are on a chromosome
– The more likely they are to be separated
during crossing over
– Linked genes, so far apart on a chromosome
that the recombination frequency is 50%, are
indistinguishable from unlinked genes that
assort independently.
– Linked genes that are far apart can be
mapped using intermediate genes
9
Many Fruit Fly Genes
• Were mapped initially using recombination
frequencies
I
Y
II
IV
III
X
Mutant phenotypes
Short
aristae
Black
body
0
Figure 15.8
Long aristae
(appendages
on head)
Cinnabar Vestigial Brown
eyes
wings
eyes
48.5 57.5 67.0
Gray
body
Red
eyes
Normal
wings
104.5
Red
eyes
Wild-type phenotypes
Linkage Groups Correspond to Chromosomes
• Sturtevant and his coworkers mapped other
Drosophila genes in linear arrays
– Crossover data clusters known mutations into
four major linkage groups.
– Drosophila has four sets of chromosomes, so
this clustering is evidence of genes on
chromosomes.
Genetic Mapping
• Types of mapping
– Maps based on crossover gives the relative
position of linked genes.
– Cytogenetic maps: locate genes with
respect to chromosomal features, such as
stained bands that can be viewed.
– The ultimate genetic maps are constructed
by sequencing DNA; in this case, distances
between gene loci can be measured in
nucleotides.
10