Lecture 12 – Mendel and the
Gene Idea
In this lecture….
• What’s a gene?
• Mendel’s pea plants
• Mendel’s hypothesis
– Four laws
• Beyond Mendel
–
–
–
–
–
Different levels of dominance
Multiple alleles
One gene producing multiple phenotypes
Multiple genes producing one phenotype
Nature vs. nurture
• Genetic Testing
• Punnet Squares
– Monohybrid crosses
– Dihybrid crosses
First…let’s define these gene things
• Genome – the full complement of genetic
information
• Chromosome – a single molecule of DNA.
There are 23 chromosomes in the haploid
genome
• Gene – a single unit within the genome that
encodes for a trait
• Nucleotide – makes up genes, chromosomes,
and genomes
Genome = Book
Chromosome = the separate chapters of
the book
Gene = a single word
Nucleotide = a single letter
What a gene looks like:
1
agtgaaatat tttaagatcc ttagaaatat aatatcaata ctatgccatt ggaggattgg
61
agggttgtga aaaacaaaca agcaaacaaa aaacggagtc ttcactgctt gatggaggct
21
tttgattcag tattggaatt ctttatccag tagttatccc ctttctatat tcatttggat
181
aaagctttcc tgggtataga acccacttag cctgcaagat tccatcccag agcaattgat
614401 ttcaactctt catgtcatga tgatagcact gaagaggtca tcaatttgaa agtggactag
614461 ctg
Definition of a gene
• Evolutionary biologist: a self-replicating unit within the DNA
that is acted on by evolutionary forces as it is passed through generations
• Molecular biologist: a segment of DNA that begins and ends
with specific nucleotide sequences
• Biochemist: A portion of DNA that is translated into a protein product
• Student: that DNA stuff
For us: a gene is a word
 Discrete
 Very specific spelling
 Produces a specific sound
(protein)
Mendel was a big thinker
• Genetics is the study of inheritance, or how
genes are passed along generations
– Genomics is the study of all genes and their
interactions with themselves and their
environment
Why do we need to know about
Mendel?
• “Father of Genetics”
• Mendel laid down the basic laws of inheritance
• He did this by experimenting with pea plants
Why pea plants?
• Advantages of pea plants for genetic study
– There are many varieties with distinct heritable
features, or traits (such as flower color)
– Mating can be controlled
– Each flower has sperm-producing organs
(stamens) and egg-producing organ (carpel)
– It was easy to control the pollination of the
plants
Model Organisms
Some vocabulary
• In a typical experiment, Mendel mated two
contrasting, true-breeding varieties, a process
called hybridization
• The true-breeding parents are the P generation
• The hybrid offspring of the P generation are
called the F1 generation
• When F1 individuals self-pollinate or crosspollinate with other F1 hybrids, the F2 generation
is produced
EXPERIMENT
P Generation
(true-breeding
parents)
Figure 14.3-1
Purple
flowers
White
flowers
EXPERIMENT
P Generation
(true-breeding
parents)
F1 Generation
(hybrids)
Figure 14.3-2
Purple
flowers
White
flowers
All plants had purple flowers
Self- or cross-pollination
EXPERIMENT
P Generation
(true-breeding
parents)
Figure 14.3-3
Purple
flowers
White
flowers
F1 Generation
(hybrids)
All plants had purple flowers
Self- or cross-pollination
F2 Generation
705 purpleflowered
plants
224 white
flowered
plants
Mendel’s Observations
• Mendel saw that the white color disappeared
in the F1 generations
• However, it persisted somehow and came
back out in the F2 generation
• Mendel called the purple flower color a
dominant trait and the white flower color a
recessive trait
Mendel’s Hypothesis
• Mendel developed a hypothesis to explain the
3:1 inheritance pattern he observed in F2
offspring
• Four related concepts make up this model
• These concepts can be related to what we
now know about genes and chromosomes
Four Concepts:
Alleles
Everyone
inherits two
alleles, one
from each
parent
Dominant
and recessive
alleles
Law of
Segregation
First Concept: Alleles
• Alternative versions of genes account for
variations in inherited characters
• For example, the gene for flower color in pea
plants exists in two versions, one for purple
flowers and the other for white flowers
• These alternative versions of a gene are now
called alleles
• Each gene resides at a specific locus on a
specific chromosome
Loci
The physical location of a gene within the genome
Mouse IGH loci map
Second: Two alleles from each parent
• For each trait, an organism inherits two
alleles, one from each parent
• The two alleles at a particular locus may be
identical, as in the true-breeding plants of
Mendel’s P generation
• Alternatively, the two alleles at a locus may
differ, as in the F1 hybrids
Homozygous vs. Heterozygous
• An organism with two identical alleles for a character
is homozygous for the gene
• An organism that has two different alleles for a gene
is heterozygous for the gene
– Unlike homozygotes, heterozygotes are not true-breeding
Third: dominant and recessive alleles
• The dominant allele determines the
organism’s appearance
• The recessive allele has no noticeable effect
on appearance
– The dominant allele masks the effect of the
recessive allele
• In the flower-color example, the F1 plants had
purple flowers because the allele for that trait
is dominant
How can one allele be dominant over the other?
• There is no one-size fits all answer
– The recessive allele makes a ‘broken’ protein
– The dominant protein stops or slows down the
recessive protein
• P53 tetramers
– The dominant protein does something new, or
does its normal thing at the wrong time
Red hair and recessive alleles
• Red hair is a recessive allele
• A protein called MC1R gets rid of red-colored
protein in hair
– MC1R is a G-protein coupled receptor
– All it take is a little bit of MC1R to do this
• If the gene for MC1R is ‘broken,’ this protein
doesn’t work
• A person must have two damaged MC1Rs to have
red hair
Frequency of Dominant Alleles
• Dominant alleles are not necessarily more
common in populations than recessive alleles
• For example, one baby out of 400 in the United
States is born with extra fingers or toes
• The allele for this unusual trait is dominant to the
allele for the more common trait of five digits per
appendage
• In this example, the recessive allele is far more
prevalent than the population’s dominant allele
Polydactylyl is a dominant trait
Hemmingway Cats
Fourth: Law of Segregation
• The two alleles for a heritable character
separate (segregate) during gamete formation
and end up in different gametes
• Thus, an egg or a sperm gets only one of the
two alleles that are present in the organism
• This segregation of alleles corresponds to the
distribution of homologous chromosomes to
different gametes in meiosis
• This is called the law of segregation
Genotype vs. Phenotype
• Genotype is the genetic makeup
• Phenotype is the physical appearance
produced by the genotype
• An organism that is heterozygous for a
recessive allele, such as albinism, would
exhibit the normal phenotype (normal color)
but have the heterozygous genotype
Phenotype
3
Figure 14.6
Genotype
Purple
PP
(homozygous)
Purple
Pp
(heterozygous)
1
2
1
Purple
Pp
(heterozygous)
White
pp
(homozygous)
Ratio 3:1
Ratio 1:2:1
1
Keeping your terms straight
•
•
•
•
Homozygous – two of the same alleles
Heterozygous – two different alleles
Genotype – the genetic composition
Phenotype – the physical appearance
• A dominant allele is signified by a capital letter
– R for having functioning MC1R
• A recessive allele is signified by a lower-case letter
– r for having defective MC1R
Writing out homozygous vs. heterozygous
A human will have two alleles of a gene – one from each parent
A person homozygous recessive for red hair will have:
Genotype: aa
Phenotype: red hair
A person heterozygous for red hair will have:
Genotype: Aa
Phenotype: Brown/black hair
A person homozygous dominant for red hair will have:
Genotype: AA
Phenotype: Brown/black hair
Dominant and Recessive Traits in
Humans
• Many (in fact, most) human traits don’t follow
simple dominant and recessive patterns
• However, there are a few that do:
– Widow’s peak (dominant)
– Attached (dominant) vs. free earlobe (recessive)
– Photic sneeze reflex (dominant)
– Wet (dominant) or dry (recessive) ear wax
– Albinism (recessive)
Widow’s
peak
Wet earwax
No widow’s
peak
Attached
earlobe
Dry earwax
Free
earlobe
Your classmate’s phenotypes
Dominant
Recessive
Ear Wax
13
7
Widow’s Peak
2
20
Photic Reflex
2
20
Earlobe
2
20
Albino
22
0
Don’t Know!?
Mendel wasn’t the end of it…
• Inheritance of characters by a single gene may
deviate from simple Mendelian patterns:
– When alleles are not completely dominant or
recessive
– When a gene has more than two alleles
– When a gene produces multiple phenotypes
– When multiple genes produce one phenotype
When a gene has more than two alleles
• Most genes have more than two alleles
• There are three alleles for blood type:
– IA, IB, and I
• IA allele adds an “A” glycoprotein to the surface of
red blood cells
• IB has adds a “B” glycoprotein
• i adds no glycoprotein whatsoever
When a gene produces multiple
phenotypes
• Most genes have multiple phenotypes, a
property called pleiotropy
• Pleiotropic alleles are responsible for the
multiple symptoms of certain hereditary
diseases, such as cystic fibrosis and sickle-cell
disease
Examples of pleiotropy
• The frizzle gene in chickens
– The dominant frizzle gene in chickens produces curled feathers,
abnormal body temperatures, high metabolic rate, and high
digestive capacity
Examples of pleiotropy
• White fur and blue eyes in cats
– 40% of cats with white fur and blue eyes will be deaf
– One particular gene causes the white coat, blue eyes, and
deafness, but not all cats get their white coat and blue
eyes from this gene
– Pigmentation plays a role in maintaining fluid in ear canals.
Animals that lack the pigment also lack ear canal fluid,
which causes their ear canals to collapse
Antagonistic pleiotropy
• P53 causes damaged cells to stop reproducing
• It decreases the chance of cancer occurring,
but also prevents stem cells from dividing
• P53 increases fitness and reproductive ability
early on in life, but decreases fitness later
Different levels of dominance
• Complete dominance occurs when
phenotypes of the heterozygote and dominant
homozygote are identical
• In incomplete dominance, the phenotype of
F1 hybrids is somewhere between the
phenotypes of the two parental varieties
• In codominance, two dominant alleles affect
the phenotype in separate, distinguishable
ways
Complete dominance
• Phenotypes of the heterozygote and the
dominant homozygote are identical
• Traditional Mendelian dominance
• Polydactylyl, albinism
Incomplete dominance
• One allele is incompletely dominant over the other
• This results in a phenotype that is intermediate
between the two alleles
• Snapdragon and carnation flower coloring
Codominance
• The contributions of two alleles contribute to
the phenotype
• Blood type in humans and roan fur in cattle
Codominance in blood type
Multiple genes having one phenotype
• In epistasis, a gene at one locus alters the
phenotypic expression of a gene at a second
locus
• For example, in Labrador retrievers and many
other mammals, coat color depends on two
genes
• One gene determines the pigment color (with
alleles B for black and b for brown)
• The other gene (with alleles C for color and c for
no color) determines whether the pigment will be
deposited in the hair
Figure 14.12
BbEe
Eggs
1/
4 BE
1/ bE
4
1/
4 Be
1/
4
be
Sperm
1/
4 BE
BbEe
1/
4 bE
1/
4 Be
1/
4 be
BBEE
BbEE
BBEe
BbEe
BbEE
bbEE
BbEe
bbEe
BBEe
BbEe
BBee
Bbee
BbEe
bbEe
Bbee
bbee
9
: 3
: 4
Polygenic Inheritance
• Polygenic inheritance is the additive effect of
two or more genes on a phenotype
• Polygenic inheritance results in quantitative
traits, traits which vary along wide a spectrum
• Human skin color is a result of polygenic
inheritance
Figure 14.13
AaBbCc
AaBbCc
Sperm
1/
1/
8
8
1/
8
1/
8
1/
8
1/
8
1/
8
1/
8
1/
8
1/
8
1/
8
Eggs
1/
8
1/
8
1/
8
1/
8
1/
8
Phenotypes:
Number of
dark-skin alleles:
1/
64
6/
64
15/
64
20/
64
15/
64
0
1
2
3
4
6/
64
5
1/
64
6
The Environmental Impact on
Phenotype
• Nature vs. Nuture
• Phenotype can depend on the environment
• For example, hydrangea flowers of the same
genotype range from blue-violet to pink,
depending on soil acidity
Twin Studies
• Two identical twins separated at birth are later
reunited and compared
• Twin studies attempt to distinguish between
genetic and environmental causes
Epigenetics
• The study of heritable changes in phenotype
caused by something other than a change in
the underlying DNA sequence
• Environmental triggers may cause these
epigenetic changes
– In mice, exposure to bisphenol A in the womb
causes the growth of yellow fur and obesity
Multifactorial traits
• Multifactorial traits are those caused a
combination of genetics and environment
– Heart disease, cancer, obesity
• It is very difficult to tease out exactly how
much of a trait is caused by a gene, and how
much by the environment
Expanding our idea of a phenotype
• An organism’s phenotype includes its physical
appearance, internal anatomy, physiology, and
behavior
• An organism’s phenotype reflects its overall
genotype and unique environmental history
• Your genes are not your destiny
Mendelian genetics still applies to
humans
• ….Sometimes
• Many genetic disorders are inherited in a
recessive manner
• These range from relatively mild to lifethreatening
Recessive alleles and diseases
• Recessively inherited disorders show up only
in individuals homozygous for the allele
• Carriers are heterozygous individuals who
carry the recessive allele but are
phenotypically normal; most individuals with
recessive disorders are born to carrier parents
• Albinism is a recessive condition characterized
by a lack of pigmentation in skin and hair
Albinism is a recessive disorder
Parents
Normal
Aa
Normal
Aa
Sperm
A
a
A
AA
Normal
Aa
Normal
(carrier)
a
Aa
Normal
(carrier)
aa
Albino
Eggs
Recessive alleles and diseases
• If a recessive allele that causes a disease is rare,
then the chance of two carriers meeting and
mating is low
• Consanguineous matings (i.e., matings between
close relatives) increase the chance of mating
between two carriers of the same rare allele
• Most societies and cultures have laws or taboos
against marriages between close relatives
Inbreeding
• The royal family of Spain inbred for
generations
• Prince Charles II:
Dominant Alleles and Diseases
• Some human disorders are caused by
dominant alleles
• Dominant alleles that cause a lethal disease
are rare because they breed themselves out of
the population
• They often arise by mutation
• Achondroplasia is a form of dwarfism caused
by a rare dominant allele
Achondroplasia
• Tyrion
Huntington’s Disease
• The timing of onset of a disease significantly
affects its inheritance
• Huntington’s disease is a dominant,
degenerative disease of the nervous system
• The disease has no obvious phenotypic effects
until the individual is about 35 to 40 years of
age
• Once the deterioration of the nervous system
begins the condition is irreversible and fatal
Huntington’s Disease
• Length of repeats in the Htt gene determines
if and when the disease will strike
• Exact mechanism of pathogenesis not known
Cystic Fibrosis
• The most common lethal genetic disease in the
United States, striking one out of every 2,500
people of European descent
• The cystic fibrosis allele results in defective or
absent chloride transport channels in plasma
membranes leading to a buildup of chloride ions
outside the cell
• Symptoms include mucus buildup in some
internal organs and abnormal absorption of
nutrients in the small intestine
Cystic Fibrosis
• Body produces abnormally thick and sticky mucus
that builds up in the lungs
• A transport protein responsible for regulating sodium
and chloride transport across cell membranes is
defective
• 1 in 25 Caucasians is a carrier
• No cure except lung transplant
Sickle Cell Anemia
• Sickle-cell disease affects one out of 400
African-Americans
• The disease is caused by the substitution of a
single amino acid in the hemoglobin protein in
red blood cells
• In homozygous individuals, all hemoglobin is
abnormal (sickle-cell)
• Symptoms include physical weakness, pain,
organ damage, and even paralysis
Sickle Cell Anemia
• Heterozygotes (said to have sickle-cell trait) are
usually healthy but may suffer some symptoms
• About one out of ten African Americans has sickle
cell trait, an unusually high frequency of an allele
with detrimental effects in homozygotes
• Heterozygotes are less susceptible to the malaria
parasite, so there is an advantage to being
heterozygous
Sickle Cell Anemia
• The malaria parasite is relatively big, and has
trouble entering sickle-shaped cells
Genetic Testing and Counseling
• Genetic tests exist that can identify carriers of
a disease allele
• Genetic counselors can then work with the
person to identify their best course of action
• Testing can also be done on fetuses to
determine if any genetic abnormalities are
present
At-Home Genetic Tests
• Some companies are offering genetic tests you
can take at home
• These tests cannot tell you anything truly
useful yet
Genetics Problems
Genetics problems will ask you to predict the
genotypes/phenotypes of the offspring given the
genotypes/phenotypes of the parents
Constructing Punnet Squares lets you predict the outcome of a cross between
two parents
They show every possible genotype and phenotype between one maternal
allele and one paternal allele
Why do Punnet Squares?
• They allow you to estimate the probabilities
of seeing certain traits in subsequent
generations
• However, they have their limits
– Few human traits follow simple
dominant/recessive patterns
Types of Punnet Squares
• Monohybrid crosses
– Involve one gene
• Dihybrid crosses
– Involve two genes
• Trihybrid crosses
– Involve three genes
Monohybrid cross
Homozygous dominant
Homozygous recessive
AA x aa
1. Determine your gametes. Remember, the genotypes given above are for
diploids. Gametes are haploid, and so will have only one allele (law of
segregation)
Gametes for AA: A and A
Gametes for aa: a and a
2. Arrange your gametes across the side and top of the square
A
A
a
Aa
Aa
a
Aa
Aa
3. Combine your gametes into your new offspring
Monohybrid cross
Homozygous dominant
Homozygous recessive
AA x aa
A
A
a
Aa
Aa
a
Aa
Aa
4. Write out your new genotype and phenotype ratios
Genotype ratio 1:1:1:1 Aa
(No phenotypes were given)
Monohybrid cross
A man who is heterozygous for attached earlobes has children with a
woman who is also heterozygous for attached earlobes. What are the
possible genotypes and phenotypes of their children? Attached earlobes
are a dominant trait.
1.
2.
3.
4.
Choose the letter you want to represent for earlobe attachment
Determine the genotypes of the parents
Determine the gametes of the parents
Write out your Punnet Square
Woman
Man
Heterozygous
Ee x Ee
E
Heterozygous
e
E
EE
eE
Genotype ratio:
1:2:1, EE:Ee:ee
e
Ee
ee
Phenotype ratio:
3:1, attached earlobe: free earlobe
Dihybrid cross
AaBb x AaBb
1. Determine your gametes
Gametes for AaBb: AB, Ab, aB, ab
Gametes for AaBB: AB, Ab, aB, ab
AB
2. Write out your Punnet Square
and arrange the gametes across
the top and side
Ab
aB
ab
AB
AABB
AABb
AaBB
AaBb
Ab
AABb
AAbb
AaBb
Aabb
aB
AaBB
AaBb
aaBB
aaBb
ab
AaBb
Aabb
aaBb
aabb
Genotype ratio:
1:2:1:2:4:2:1:2:1
Phenotype ratio:
9:3:3:1
Codominance
A heterozygote for blood type A is crossed with a heterozygote for blood type
B. What are the possible genotype and phenotype ratios of their children?
Heterozygote Type A
Heterozygote Type B
IAi x IBi
IB
i
IA
IAIB
IA i
i
IBi
ii
4. Write out your new genotype and phenotype ratios
Genotype ratio 1:1:1:1, IA IB : IA i : IB i: ii
Phenotype ratio: 1:1:1:1 Type AB: Type A: Type B, Type O
Epistasis
Two Labrador retrievers that are heterozygous for two genes are crossed.
These two genes control pigment depositing and coat color. Without a
functional copy of the pigment depositing gene, the color will not be
expressed regardless of whether it is brown or black.
For example, in Labrador retrievers and many other
mammals, coat color depends on two genes
One gene determines the pigment color (with alleles B for
black and b for brown). Black is the dominant color.
The other gene (with alleles E for color and e for no color)
determines whether the pigment will be deposited in the
hair. Color depositing is the dominant trait.
Epistasis is by necessity a dihybrid cross!
Epistasis
BbEe
BbEe
BE
BE
Be
bE
be
BBEE
BbEE
BBEe
BbEe
BbEE
bbEE
BbEe
bbEe
BBEe
BbEe
BBee
Bbee
BbEe
bbEe
Bbee
bbee
bE
Be
be
9
: 3
: 4
Sex-linked traits
The trait for red-green colorblindness is sex-linked. Normal vision is
dominant to colorblindness. A normal-visioned man, whose father had redgreen colorblindness, marries a red-green colorblind woman.
Non-colorblind man
Colorblind woman
XN Y x Xn Xn
XN
Y
Xn
X NX n
XnY
Xn
X NX n
XnY
4. Write out your new genotype and phenotype ratios
Genotype ratio 2:2, XNXn : XnY
Phenotype ratio: 2:2 normal female: colorblind male
Practice Problems
• http://biology.clc.uc.edu/courses/bio105/gen
eprob.htm
Highly recommended!!!
Further Links
• Online Mendelian Inheritance in Man – the
premier database on Mendelian genetic
disorders
– http://www.ncbi.nlm.nih.gov/omim
• How MC1R causes red hair
– http://ghr.nlm.nih.gov/gene/MC1R
• More on how dominant alleles can be
dominant
– http://www.thetech.org/genetics/ask.php?id=227
Further links
• More on epigenetics
– http://learn.genetics.utah.edu/content/epigenetic
s/
• More on incomplete vs. codominance
– http://www.hobart.k12.in.us/jkousen/Biology/inc
codom.htm
• More on polydactyl cats
– http://www.messybeast.com/polycats.html#genes
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Vocabulary
Parental, F1, F2 generation
Test cross
Genome, chromosome, gene, nucleotide
Dominant, recessive
Genotype, phenotype
Pleiotropy
Complete dominance
Incomplete dominance
Codominance
Epistasis
Polygenic inheritance
Quantitative characteristics