Transcript Introduction and Mendelian Analysis

Prior history
To appreciate Mendels work, one must keep in mind the
prevailing theories of inheritance
Mendel ignored development, focused solely on transmission of traits
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Darwin and Heredity
Darwin: Among individuals of any species, there are
differences (variations)
Evolution cannot occur unless there are differences
among individuals
Variation is important
Mechanism of inheritance is important for
understanding evolution
Mechanism of inheritance not understood
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Pangenesis
Pangenesis: (1860s)
Whole organism reproduces itself
Gemmules
Germ cells contain gemmules
Fertilization- gemmules unite
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Cytology:
Cytology
1600s Organisms are composed of cells
1830s The most distinct structure in a cell is the
nucleus. ALL cells have a nucleus.
1840s Cells are formed by the division of preexisting cells (Mitosis)
1850s Sperm and Ovum are cells.
1873 Mitosis described in detail
1883 Fertilization in sea urchin
1885 Meiosis described
Reductional division
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Cytology’s contribution prior to Mendel
Heredity is a consequence of genetic continuity of cells
by division
Germ cells are the vehicle of transmission from one
generation to the next
Nucleus is crucial.
Fertilization involves union of sperm and eggs
Fertilization involves union of nuclei
Chromosomes do not lose their individuality.
Germ cells contain half the number of chromosomes
found in body cells.
Diploid embryo descends from maternal/paternal fusion
of haploid chromosome groups
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The origin of genetics:
The study of genetics begins when Gregor Mendel, in 1865,
addressed the question :
"How are characters passed on from one generation to the
next?”
Mendel was the first to make a serious attempt of
experimentally answering the question of heredity and not only
were his answers correct, they were a complete and compelling
proof.
Mendel published in 1866 but little attention was paid to his
work until 1900, when it was simultaneously rediscovered by
three scientists, one in Holland, one in Austria, and one in
Germany.
There are often impressions that Mendel was removed from the
scientific community, or that his papers were not well
circulated.
This was not true. Over 200 copies of Mendels papers have
been discovered in different libraries.
All three of Mendel's rediscovers had read Mendel's work prior
to publishing their own work.
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Gregor Mendel was born on either 20th or 22nd July, 1822 in
Heizendorf (today Hynice in the Czech Republic).
From 1851 to 1853, Gregor Mendel studied zoology, botany,
chemistry, and physics at the University of Vienna.
He studied botany under Prof. Unger where he learned crosses
He studied physics under Prof. Doppler where he learnt
statistics
Mendel returned to Brno and began his experiments with the
hybrid cultivation of pea plants in 1856.
After spending eight years carrying out experimental work in
the monastery garden, he reported on the results of his
observations at the meetings of the Association for Natural
Research in Brno on the evenings of February 8th and March
8th, 1865
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Model organisms
A model organism is
Model organisms are used to obtain information about other
species – including humans – that are difficult to study directly.
Genetic model organisms
Experimental model organisms
Genomic model organisms
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Model organisms
Human model organisms
Relevance of model organisms to humans.
Modern genetics:
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The Pea
Mendel chose the common garden pea to study patterns of
inheritance. This was a excellent choice as a model system
for the following reasons:
1
2
3
4
He identified over 20 traits and studied 7
Seed shape:
Seed color:
Flower color:
Pod shape:
Pod color:
Flower position:
Stem length:
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True breeding
The first two years of Mendel's work were devoted to
selecting lines that breed true (pure lines) for a particular
character or trait.
He identified over 20 traits that bred true and studied 7
Breeding True:
He identified plants that produced only round seeds and
plants that produced only wrinkled seeds.
He identified plants that produced only purple flowers and
plants that produced only white flowers.
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Mendel’s first cross
P
F1
F2
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Mendel’s first cross
P
F1
F2
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Keys to success
He did these experiments with all seven traits!!!!
The ratios obtained were between 2.82:1 and 3.15:1
This cross involving only one character, seed color, is called a
monohybrid cross.
Keys to success:
1
2
3
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Conclusions
Although others were doing similar experiments at the time,
Mendel work was unique
Results and Conclusions:
1
2
3
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Mendels monohybrid cross
YY
x
yy
Yy
x
Yy
1YY:2Yy:1yy
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Results and Conclusions:
1
In F1 all progeny showed the same trait for all
crosses
2
Males and females was not important
3
Character missing in F1, reappeared in F2
Traits did not blend in the offspring but were transmitted in
a discrete fashion and remained unchanged.
Reciprocal crosses produced the same results, this
indicated that each parent makes an equal contribution to
genetic makeup of the offspring.
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All F1 seeds were yellow but when selfed the F2 produced some
green seeds.
Mendel termed the trait that is expressed in the F1 as dominant
The trait that is hidden but re-expressed in the F2 as recessive.
The F1 plants must contain factors for green and yellow since
both are found in the F2.
With these assumptions the simplest model is that the F1 contains
two hereditary factors
One for green and another for yellow
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The parents have two factors, they produce gametes
containing only a single factor
Parent
YY
Gamete
1/2Y
F1
yy
1/2Y
1/2y
1/2y
1/2Y 1/2y
Sperm and egg randomly combine to produce F2 progeny
Mendel reasoned that without a mechanism to halve the
number of factors in each generation, that factors would
multiply with each generation and become unmanageable.
Mendel reasoned that during gamete formation the paired
factors separate and each gamete receives one of the two
factors.
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Terms
Phenotype and genotype: The parental yellow pea plants are a
pure line- they only produce yellow pea plants when selfed.
Same is true for green
However the F1 yellow pea plants produce some green pea plants
when selfed. These F1 yellow plants are different from the
parental yellow plants.
Therefore it is necessary to make the distinction between the
appearance of an organism and its genetic make-up.
Phenotype refers to appearance of an organism to the eye.
Genotype refers its genetic makeup.
Would say the parental yellow pea plants and F1 yellow pea plants
have the same phenotype but a different genotype.
P
F1
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Terms:
Dominant and recessive: All F1 seeds were yellow but when
selfed the F2 produced some green seeds.
Mendel termed the trait that is expressed in the F1 as
dominant
The trait that is hidden but re-expressed in the F2 as
recessive.
The F1 plants must contain factors for green and yellow since
both are rediscovered in the F2.
From the fact the reciprocal crosses produce the same result,
Mendel concluded that male and females contribute equally
With these assumptions the simplest model is that the F1
contains two hereditary factors
One for green and another for yellow
Mendel used the Uppercase Y to represent the dominant yellow
factor and the lower case y to represent the recessive green.
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The Principle of Segregation:
Mendel reasoned that without a mechanism to halve the number
of factors in each generation, that factors would multiple with
each generation and become unmanageable.
Mendel reasoned that during gamete formation the paired
factors separate and each gamete receives one of the two
factors.
Parent
Gamete
F1
Notice that while the parents have two factors, they produce
gametes containing only a single factor
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YY
Yellow
yy
Green
Grows into
A plant
Grows into
A plant
Generates
Gametes
Generates
Gametes
Y
Or
Y
y
Or
y
Gametes combine at Random
Yy
Yellow
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Mendel's assumption of two factors and segregation makes
a strong prediction concerning the genetic make-up of the of
F2 yellow pea plants:
F1
Y
Yy
X
y
Yy
Y
y
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Selfing
Of the yellow F2 plants, 1/3 should be YY and 2/3 Yy
How would you test this prediction?
Mendel selfed each of the green F2 plants
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Selfing
Mendel selfed each of the green F2 plants
Green
yy
F3
X
X
Green
yy
yy
green
All green plants
120 green F2 were selfed:120 green seen
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Selfing
Mendel selfed each of the yellow F2 plants
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Probability
Cross
Yy x Yy pea plants.
Chance
of Y sperm uniting with a Y egg
___chance of sperm with Y allele
___ chance of egg with Y allele
Chance of Y and Y uniting =
=
Chance
of Yy offspring
___ chance of sperm with y allele and egg
with Y allele
___ chance of sperm with Y allele and egg
with y allele
Chance
of Yy = (
x
) + (
x
) =
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Probability
Cross
Yy xYy pea plants.
Chance
of Y sperm uniting with a Y egg
(1/2) chance of sperm with Y allele
(1/2) chance of egg with Y allele (1/2)
Chance of Y and Y uniting = 0.5 x 0.5 = (1/4)
Chance
of Yy offspring
1/4 chance of sperm with y allele and egg
with Y allele
1/4 chance of sperm with Y allele and egg
with y allele
Chance of Yy = (0.5x0.5) + (0.5x0.5) = 0.5
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Test cross
If instead of selfing the F2 plants, they are crossed to
pure breeding green plants, what are the expected outcomes:
F2
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More terms:
Mendel's factors are now known as genes
Alternative forms of a gene that determine different traits are
known as __________
Individuals with two identical alleles are said to be __________
Individuals with two different forms of alleles are said to be
_____________
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The dihybrid cross and the principle of independent
assortment:
In the second set of experiments Mendel investigated the
pattern of inheritance for two sets of characters simultaneously.
A cross involving two sets of characters is called a dihybrid cross.
Pea shape: smooth, wrinkled (Smooth is dominant to wrinkled)
Cotyledons color: yellow, green (Yellow is dominant to green)
P
x
F1
selfed
F2
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The 9:3:3:1 ratio.
The 9:3:3:1 ratio is a lot more complex than the 3:1 ratios of
the monohybrid crosses.
Mendel's insight was to realize the 9:3:3:1 ratio is nothing
more than two 3:1 ratios combined at random. That is if one
examined the traits individually they formed a 3:1 ratio.
To determine the mode of inheritance of the two genes in this
dihybrid cross Mendel examined each of the traits separately:
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9:3:3:1 ----> 3:1
If we examine only seed shape (smooth, wrinkled) and ignore
cotyledon color (yellow, green), in the F2, we expect to find:
3/4 smooth and 1/4 wrinkled:
# Smooth =
#wrinkled =
In addition, if we only examine cotyledon color,
we expect 3/4 Yellow to 1/4 green.
#Yellow =
#green =
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Each trait behaves as a standard recessive found in a
monohybrid cross.
They do not affect one another
Genes segregate independently!!!!
GeneA in a gamete does not affect the segregation of geneB in
that gamete.
Parent
Gamete
F1
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In a heterozygous individual (self cross)
SsYy
x
SsYy
Genes line up in two ways during gamete formation
Gamete
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In a heterozygous individual with two traits
SsYy
x
SsYy
Genes line up in two ways during gamete formation giving rise
to 4 different gametes
SsYy
SsYy
SY
sy
Gamete
Sy
sY
or
SY
sy
Sy
sY
25%
25%
25%
25%
Mendel concluded that SsYy individuals produced the following
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gametes in a 1:1:1:1 ratio SY Sy sY sy
Independent assortment
If independent assortment is occurring, four different kinds of
gametes will be produced in equal frequencies.
The only rule is that S and s segregate to separate gametes and
Y and y segregate to separate gametes;
(that is one does not get an Ss gamete or a Yy gamete)
SsYy males and SsYy females can produce four types of gametes
in equal frequencies:
SY, Sy, sY, sy
The male and female gametes randomly combine to restore diploidy
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Mendels dihybrid cross
YYSS x
yyss
YySs
x
YySs
9Y-S-:3Y-ss:3yyS-:1yyss
Different gene pairs assort independently during gamete
formation.
The presence of a Y in a gamete does not influence the
probability of a S or s being in that gamete.
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Calculation
A heterozygous Red eyed curly winged female fly is
crossed to a heterozygous Red eyed curly winged male
fly.
What is the expected ratio for a Red eyed flat
winged male fly?
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Punnet diagram of a dihybrid cross
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Branched Diagram
If you combine the monohybrid ratios for two PHENOTYPES
you get:
3/4 smooth
1/4 wrinkled
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Probability
Yellow is dominant to green
Smooth is dominant to wrinkled
Heterozygous yellow
Heterozygous smooth
X
Heterozygous yellow
Homozygous wrinkled
Probability of yellow wrinkled?
smooth
yellow
wrinkled
green
Heterozygous yellow
Homozygous smooth
X
Heterozygous yellow
Homozygous wrinkled
Probability of yellow wrinkled?
smooth
yellow
wrinkled
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More probabilities
Yellow is dominant to green
Smooth is dominant to wrinkled
Tall is dominant to short
Heterozygous yellow
Heterozygous smooth
Heterozygous tall
X
Heterozygous yellow
Homozygous wrinkled
Heterozygous tall
Probability of green wrinkled short?
smooth
green
tall
wrinkled
short
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What is the biological significance of the 9:3:3:1 ratio?
This ratio is only produced if TWO DIFFERENT GENE PAIRS
assort independently of each other during gamete formation.
The presence of one gene in a gamete does not influence
the probability of another gene being found in that gamete
Principle of segregation: for one gene, each individual has two
copies.
These two copies segregate from one another during gamete
formation.
Independent assortment: Segregation of one gene pair is
independent of the segregation of any other pair of gene.
Hence the 9:3:3:1 ratio and the biological significance of
Mendel's second lawDifferent gene pairs assort independently during gamete
formation.
The presence of a Y in a gamete does not influence the
probability of a S or s being in that gamete.
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Mendels laws
1.
The principle of segregation: Each individual carries two
copies of a given gene and these segregate from one another
during gamete formation.
2. The principle of independent assortment: The segregation of
one pair of genes is independent of the segregation of any
other pair of genes during gamete formation
(as we will find their are important exceptions to this rule)!!!!!
By applying these rules Mendel concluded that SsYy individuals
produced the following gametes in a 1:1:1:1 ratio
SY Sy sY sy
As described above, he inferred these gamete ratios by selfing
SsYy individuals.
He could also have inferred these gamete ratios by crossing
SsYy individuals to ssyy individuals.
Crossing to the homozygous recessive individuals is known as a
test cross
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Test cross
A test cross is easier that a self cross for the F2
What are the expected genotypic and phenotypic ratios of
the progeny produced from this cross?
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Gene number
Power of Mendel phenotype ratios:
The ratio tells you the number of genes involved in determining a
phenotype
3;1 ratio (selfing) = 1 gene
9:3:3:1 ratio (selfing) = 2 genes
27:9:9:9:3:3:3:1 ratio (selfing) = 3 genes
Say seed color is controlled by two genes- GeneS and GeneT
Green seeds are sstt
All others are yellow ( if either S or T are present, the seed is yellow)
True breeding yellow
SSTT
x
F1
SsTt
(yellow)
SsTt
Self
x
true breeding green
sstt
SsTt
How many green will you get out of this cross:
These conclusions about gene number become very important when
applied to human traits like size, behavior, temperament etc. 48
Take two individuals
They both have blue eyes
They mate and produce 16 progeny
12 have blue eyes and 4 have black eyes
There is ________ gene/s for eye color
If instead you get 15 with blue eyes and 1 with black eyes
There are _______ gene/s for eye color
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Dog genome
The Dog Genome Project is an example of how basic Mendelian
principles are being used to identify genes that control
morphology and behavior.
Dr. Jasper Rine at U.C. Berkeley crossed
Newfoundlands to Border Collies.
These dogs differ extensively in size and behavior.
Newfoundlands are vigorous swimmers and weight about 140
pounds
Border Collies are herders and weigh about 50 pounds
By performing a series of Mendelian crosses one can begin to
determine how many and what kinds of genes are involved in
determining their behavior!!!!
Follow the link to Jasper's Dog genome web site (key words dog
genome will get you there)
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Dogs have been breed for specific traits for 10,000 years
About 150 breeds have been generated through selective breeding
Diversity in
Physical makeup:
Coat color
height
mass
muscle
Behavior:
herding
tracking
retrieval
Guarding
Intelligence:
The individual breeds can mate with one another and produce viable
fertile offspring
They can also mate with Cayotes and wolves
Border collies do not like water, Newfoundlands love water.
In the cross swimming is dominant!
This complex trait is likely mediated by a small number of genes (~2)
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Coat color
Coat Variation in the Domestic Dog Is Governed by
Variants in Three Genes
2 OCTOBER 2009 SCIENCE VOL 326 p150
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Specific breeds of dogs are also associated with specific diseases
Dobermans: narcolepsy
Scotties: Haemophilia
Terriers: copper metabolism (menke disease)
Labrador: hip dysplasia
Beagle: seizure risk
The ratio from a doberman cross suggests that narcolepsy is most
likely mediated by a single gene! (3:1 ratio)
Why are Mutts healthier than true breeds?
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Hybrid Vigor
Hybrid vigor:
The first cross between two purebred lines is often healthier than
either parent
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