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Chapter
4. Extensions of Mendelian Inheritance.
Simple
Mendelian inheritance is when a trait is affected by one gene with one
allele dominant over another.
The
inheritance patterns readily follow Mendels laws.
In
this chapter:
Molecular
expression of genes.
Explore
traits that do not produce the expected ratios. Doesnt mean Mendel was wrong it is just more complex.
Inheritance
patterns of single genes.
Types
of Mendelian inheritance patterns.
Recessive
alleles often cause a reduction in amount or function of the encoded
protein.
The most prevalent
allele in a population is often considered the wild-type allele.
Usually
this wild-type allele encodes for a normally functional protein and for
the proper amount.
Alleles that have
been altered by mutation are called mutant alleles.
What
are examples?
More
common for a mutant allele to have altered function or amount. »
Often
defective.
Most
genetic disorders are caused by recessive mutant alleles.
Since
diploid organisms have two copies of every gene the wild-type allele will
mask the loss of function allele in many instances. »
Not
all instances.
Heterozygotes
can sometimes be thought as having 50% function or amount of the protein. »
This
is very general and not always accurate.
For
many genes, 50% is enough for a normal phenotype.
An allele that
causes death to an organism is called a lethal allele.
Of
yeasts approximately 6,000 genes 1,200-1,500 are thought to be essential.
Nonessential
genes are not
absolutely required for survival.
Can
result in other phenotypes: like temperature sensitivity, slow growth
susceptibility to environmental factors etc.
Lethal alleles can
have varied effects including: cell cycle and environmental factors.
Ex:
Huntington's is a slow degenerative disease of the nervous system the age
of onset is not until later in life (30-50).
Others may only kill
the organism under certain conditions (conditional lethal alleles).
Ex:
oxidants, temperature and pH. Semilethal alleles will only affect certain individuals.
Incomplete
dominance
occurs when alleles produce an intermediate phenotype.
First discovered in
flower color by Carl Correns.
Crossed homozygous
red flowers with homozygous white flowers.
The
result of the F2 was Ό Red, Ό white and ½ pink.
What
do you think the genotypes of these flowers are?
Why do you think
there is incomplete dominance in this situation?
Unlike
other heterozygotes 50% of the protein is not enough to have a normal
phenotype.
Ex:
Mendels round or wrinkled seeds. »
To
the unaided eye Both heterozygous and homozygous dominant seeds look
round. »
However,
using a microscope to look at starch deposits, there is a definite
phenotypic difference between the homozygous dominant and heterozygous
peas. »
The
amount of starch deposits is different. »
So
it may depend on the phenotype examined.
Some genes
have more than two alleles.
Ex: Coat color in
rabbits:
Four
alleles C, cch, ch and c. »
C
is dominant to cch, ch and c. »
Cch
is recessive to C but dominant to ch and c. »
ch
is recessive to C
and cch but dominant to c. »
c
is recessive to C, cch and ch.
Interesting
phenotypes of the alleles: »
C
is the allele for full coat color. »
Cch
is the allele for chinchilla coat color. »
Ch
is the allele for Himalayan coat color; expresses only in certain portions
of the body, temperature-sensitive conditional allele gene only
functions at the extremities. »
C
is the allele for albino coat color; produces a nonfunctional pigment
protein. CC, Ccch, Cch or Cc are genotypes leading to full coat color.
Alleles of
ABO blood group can be dominant, recessive or codominant.
These
are the substances that are recognized by antibodies.
Three
possible antigens A, B and O. »
Three
alleles control the production of these antigens IA, IB
and i respectively. »
AB
individuals express both antigens and are codominant. »
O
individuals produce antigens that are recognized by all blood types- they
are universal donors.
Experiment
4A: Gene dosage effect on Drosophila eye color.
Early experiment (T.
Morgan again) showing that the amount of protein can play an important
role of phenotype.
Through analyzing
thousands of flies found red-eyed (Dom.), white-eyed (recessive) and a
mutation called eosin.
Males
with the eosin allele have pinkish yellow eye color and females have
yellowish pink (more intense color). »
What
do you think a possible reason could be?
Morgan and Bridges
proposed that this variation may be to X-chromosome number.
Female
has more eosin eye-color due to having two genes (due to two
X-chromosomes).
This
is an example of a gene dosage effect. »
In
this case two copies (thus two doses) of the allele provide more color
than one copy (male). Hypothesis: Phenotypic effects of the eosin eye-color allele are related to the number of copies of the allele.
Interpretation
of the Data:
Crosses
involving homozygous females for a certain eye color and males hemizygous
for a different eye color a 1:1 ratio was always observed.
Consistent with
X-linked alleles that are allelic.
Ex:
All flies with a genotype for red eyes had the same color red whether it
was 1 or 2 gene dosages. »
Xw+Xw+
phenotype (red-eyes were indistinguishable) was equal to Xw+Xw-e,
Xw+Y or Xw+Xw) »
No
gene dosage effect the red allele is dominant to white or eosin.
Unlike red-eye color
the eosin phenotype is affected by gene dosage (Xw-e allele).
Homozygous
females with two copies had eosin eyes.
Heterozygous
females and hemizygous males (Xw-e Xw, Xw-eY)
had light eosin eyes.
Morgan
and Bridges said the Xw allele of the heterozygous female was
having a dilution effect. »
Another
way to think of that is?
Supports
the idea of the amount of gene product influencing the trait.
The heterozygote may
be larger disease resistant or better able to withstand harsh
environmental conditions.
Also called heterozygote
advantage.
Ex: Sickle cell
anemia: a recessive disorder of the blood that produces an abnormal
hemoglobin protein.
Normal
alleles is HbA while individuals affected are homozygous HbS
the heterozygote HbAHbS is resistant to malaria.
Plasmodium sp. which are the causitive agent of malaria do not survive well
within HbAHbS cells.
At the molecular
level overdominance is due to two alleles that produce two protein
subunits.
A
protein that is composed of two subunits is a dimer if the subunits
are encoded by the same gene it is a homodimer.
If
a mixture of two subunits encoded by different alleles of the same gene
function better than either homozygous homodimer then you get
overdominance. »
The
heterozygous homodimer may function over a wider range of conditions or be
more stable. »
Each
different subunit may also function under different conditions like
temperature. Ex:
Used
in plant and animal breeding.
Incomplete penetrance occurs when some dominant traits skip a generation.
Individuals
occasionally will carry a dominant allele for a trait and not show the
phenotype.
The term incomplete
penetrance means that a the dominant allele does not always
penetrate into the phenotype of the individual.
Ex:
if 60% of the heterozygotes showed the dominant trait then the allele
would have 60% penetrance.
Must also evaluate
how much the trait is expressed.
Expressivity
is the variation of how the trait is expressed.
No
expression of a dominant trait is incomplete penetrance.
Ex:
polydactyly an individual may have a single extra digit or multiple (hands
or feet). »
If
they have the dominant allele and have no phenotype it is due to
incomplete penetrance.
Trait
expression may be due to environmental factors and modifier genes.
Environmental
factors like sunlight and temperature can effect the expression of a
trait.
Ex: PKU and
snapdragon flower color.
90%
of babies are tested for PKU costing a few million treatment would cost
hundreds of millions. »
Alleviates
suffering as well.
Gender
can influence traits.
Women who are
homozygous for the baldness allele (bb) often just show thinning of the
hair very late in life.
A heterozygous
female (Bb) can be completely bald if she has an adrenal tumor that is
producing male testosterone.
Bald men have about
50% bald sons this is higher if the father is homozygous or the mother
carries the allele.
Sex-limited
traits are extreme examples of gender influence on traits.
Ex: breast
development in females beard development in males.
In birds males often
have more ornate plumage, larger comb and wattles and a longer neck and
tail.
Ex:
Expression of cock feathering is due to the presence or absence of sex
hormone.
Hen feathering is
controlled by a dominant allele that is expressed in males and females.
Cock feathering is
controlled by the recessive allele and is only expressed in males.
A
female hh with her ovary removed is indistinguishable from a male
Gene
Interactions:
Traits can
be affected by the outcomes of two or more genes.
Ex: Height, weight,
growth rate and pigmentation.
Ex:
Pea Plant height; there are actually many genes that can affect plant
height Mendel only studied one.
We will
discuss three examples of two genes with two alleles.
Focus
on the outcome of a cross between two individuals AaBb X AaBb.
If these genes
governed different traits, we would expect a 9:3:3:1 ratio among the
offspring.
In
our examples the two genes will affect the same trait.
Watch
how the alleles interact to affect the trait and how it affects the
9:3:3:1 ratio.
Ex:1
Two-gene interaction can give a 9:3:3:1 ratio when four phenotypes are
produced.
First case of two
genes interacting to affect a single trait was described by Bateson and
Punnett (1906).
Four different comb
morphologies in chickens: Rose, Pea, Walnut and Single.
Crossed Rose X Pea
and the F1 was all walnut comb.
The F1
generation was crossed and there were four combs found in the F2
generation.
9
Walnut: 3 rose: 3 pea: 1 single.
Punnett and Bateson
reasoned that a single trait (comb morphology) is determined by two
different genes.
R
(rose comb) is dominant to r.
P
(pea comb) is dominant to p.
R
and P are codominant (walnut comb).
rrpp
produces single comb.
9:7 ratio
occurs when the two genes are epistatic to one another.
Bateson and Punnett
studied sweet pea plant flower color.
Found
that purple and white flower color followed Mendelian inheritance
patterns.
However,
when two varieties of white flower producing pea plants where crossed all
the offspring of the F1 generation had purple flowers.
After
allowing the F1 offspring to self-fertilize they recovered a 9
purple: 7 white ratio of flower color in the F2 offspring.
C
(one purple-color allele) allele is dominant to c (white).
P
(another purple-color producing) allele is dominant to p (white).
cc
or pp masks the P or C alleles producing white color.
A plant homozygous
for either recessive white allele will produce white flowers no matter if
there are purple producing alleles from the other gene.
Ex:
cc or pp masks any purple producing alleles.
Lose
function in either enzyme (homozygous recessive) and you do not get purple
color.
Exp. 4B
Bridges observed an 8:4:3:1 ratio in crosses of fruit flies when he found
that the cream-eye allele can modify phenotypic expression of the eosin
allele and but not red or white alleles.
Bridges found flies
with cream-colored eyes.
Could
be from two sources: »
1)
New allele, cream is from a mutation in eosin. »
2)
Mutation in a different gene is modifying the expression of the eosin
allele.
Bridges carried out
crosses to distinguish these two possibilities.
He
knew that the eosin allele was X-linked but wanted to know if cream-color
was allelic or if it was on a completely different chromosome.
C
will represent the normal allele and ca will be the eosin
modifying allele.
Hypothesis:
Cream-colored eyes in fruit flies are due to the effect of a second
gene that modifies the expression of the eosin allele.
Interpreting
the Data:
F2
generation indicates that it is not allelic to the eosin allele.
Males
would have only had cream eye color.
Their
would have been no eosin eye color at all, because males were cream and
females were homozygous reds.
Consistent with the
idea that P generation flies had alleles for both eosin and cream color.
Bridges stated that
the cream color allele was a specific modifier of the eosin eye color. Cream-color allele (ca) is an autosomal recessive allele.
Examining the
Punnett square and the phenotypic outcome you can see that the ca
allele affected eosin expression but not red.
Furthermore, this
only occurs when the offspring is homozygous for the ca allele.
The predicted
8:4:3:1 agrees reasonably well with his results.
Bridges concluded:
Specific
modifications are clear and simple cases of multiple genes. Each is
the result of the coaction of a specific modifying gene (ca),
which by itself produces little or no visible affect, and of a particular
gene (eosin) that is necessary as a base or differentiator.
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