Download Extensions to Mendelism

Extensions to Mendel’s Genetic Model
• Mendel's pea experiments used a very simple genetic
system: each gene had 2 alleles, one dominant and one
recessive, and genes did not interact with each other.
• We are going to look at some variations: different forms
of dominance, multiple alleles, interactions between
genes, and environmental effects.
• “Dominance” refers to the phenotype of the
heterozygote.
• Mendel studied complete dominance: the heterozygote
looks exactly like the dominant homozygote.
Partial (Incomplete) Dominance
• In partial dominance, the
heterozygote has phenotype
intermediate between the two
homozygotes.
• Example: Four o'clock plants.
Red flowers x white flowers
gives pink F1's. Pink is
intermediate between red and
white.
• Selfing the F1's gives 1/4 red
(RR), 1/2 pink (Rr), and 1/4
white (rr)
Co-dominance
• In co-dominance, both parental alleles
are expressed in the heterozygote.
• Example: blood groups. A glycoprotein
antigen on the surface of red blood
cells cause them to clot in the
presence of the corresponding
antibody.
• The MN blood group antigens are
coded for by the L gene: the 2 alleles
are called LM and LN.
– A LM LM homozygote has the M blood type:
blood clots in the presence of anti-M
antiserum, but not in the presence of anti-N
serum.
– Similarly, a LN LN homozygote has the N
blood type: blood clots in the presence of
anti-N antiserum, but not in the presence of
anti-M serum.
– The LM LN heterozygote has the MN blood
type: it clots with both anti-M and anti-N
antiserum. These red blood cells have both
antigens on their surface. Thus, the MN
blood group alleles are co-dominant.
Electrophoresis
• When an organism's DNA or proteins are
examined closely, almost all genes are codominant. Both alleles of the gene are
present, even if they don't contribute equally
to the phenotype.
• Electrophoresis is a way of separating DNA
or proteins on the basis of how fast they
move in an electric field.
– DNA and RNA have one negative charge per
nucleotide.
– Most proteins also have a net negative charge,
caused by 2 of the 20 amino acids, which have a
negative charge.
– Since opposite charges attract, most nucleic acids
and proteins move towards the positive pole.
• The speed the molecules move is
proportional to their charge and inversely
proportional to their size: small, highly
charged molecules move faster than large,
less charged molecules.
• Electrophoresis is done in a gel matrix, to
prevent diffusion from confusing the results.
More Electrophoresis
•
As an example, consider hemoglobin, the
oxygen-carrying protein in the blood.
– Hemoglobin has 4 polypeptide subunits: 2
alpha and 2 beta.
•
•
Most people are homozygous for the HbA
beta subunit.
The HbS allele is common in West Africa (it
confers malaria resistance).
– HbS has an uncharged valine in place of the
negatively charged glutamic acid found in HbA.
– Thus, hemoglobin containing HbS migrates
more slowly in electrophoresis than
hemoglobin containing HbA.
•
Heterozygotes have some hemoglobin with
HbA and some with HbS. This means that
both the HbA and the HbS bands appear on
the electrophoresis gel. (co-dominant)
Multiple Alleles
• Mendel used only 2 alleles per gene. Any
change in the DNA sequence of a gene is a
different allele, so there are millions of possible
alleles for any gene.
• In reality, many genes have several common
alleles: they are polymorphic. Some genes are
constrained by natural selection to have only a
single allele: they are monomorphic.
– Having 2 alleles, as in Mendel’s genes, is called
dimorphic.
• Genes with multiple alleles can have a variety of
dominance patterns between the alleles.
ABO Blood Group
• The ABO blood group is a common
multiple allele system. The gene
itself is called I, and it has 3 alleles:
IA, IB, and iO.
• IA and IB are co-dominant, and both
IA and IB are dominant to iO.
– Thus, IA IA homozygotes and IA iO
heterozygotes have type A blood.
• Similarly, IB IB homozygotes and IB iO
heterozygotes have type B blood.
• Because IA and IB are co-dominant,
IA IB heterozygotes have AB blood.
• Type O blood occurs in people with
the iO iO genotype.
– Note: O is the most common blood type.
Frequency in the population is not related to
dominance.
Major Histocompatibility Locus
• The MHC is the primary determinant of human
tissue type, which determines whether organs
can be transplanted between people without
rejection by the immune system.
• The MHC consists of 6 major genes lying close
together on one chromosome. These genes are
usually inherited as a single unit, called a
haplotype. Taken together, the MHC genes are
probably the most polymorphic region of the
human genome. There are thousands of known
haplotypes.
• Most people have 2 different haplotypes, one
inherited from each parent. Similarly, mates
usually have different haplotypes. The result of
this is that each person has one haplotype in
common with each parent and one haplotype
different. However, a person has a 1/4 chance of
having both of the same haplotypes as his/her
sibling. Thus, organ transplants between siblings
are usually the easiest to perform.
Lethal Alleles
• Many alleles that cause
genetic diseases are called
"dominant" because
heterozygotes are affected. A
common example is
achondroplasia, the most
common form of dwarfism, with
a normal length body trunk but
shortened limbs. Another in
the Manx cat, which doesn't
have a tail.
• In fact, these genes would be
better described as partially
dominant, because the
homozygotes are quite
different from the
heterozygotes: homozygotes
are lethal.
More Lethal Alleles
• Lethal alleles give an unusual inheritance ratio. Consider
a mating between two Manx cats. Each is heterozygous
Tt, with T the dominant tailless allele and t the recessive
normal tail allele.
• Using Mendel's Law of Segregation, we see that zygotes
form in the ratio of 1/4 TT, 1/2 Tt, and 1/4 tt.
• However, all the TT embryos die at a very early stage,
and only the Tt (tailless) and tt (tailed) cats are born.
• Because there are twice as many Tt as tt, the ratio of
offspring in the Tt x Tt cross is 2/3 Tt (tailless) to 1/3 tt
(tailled).
• Note that pure breeding lines of Manx cats (and
achondroplastic dwarves) can't exist, because 1/3 of their
offspring are of the incorrect type.
Phenotype Ratios for Multiple
Genes
• For more than 2 genes, Punnett squares get unwieldy.
To calculate the ratio of offspring, we use a different
method, the forked-line approach.
• To do these problems, 3 steps are involved:
1. Determine the ratio of phenotypes for each gene separately.
These ratios depend on the type of dominance as well as the
genotypes of the two parents.
2. Draw a forked line diagram of the offspring, splitting each line
for each separate gene, showing the ratio of phenotypes.
3. Combine the phenotypes and multiply the phenotype ratios
along each branch to get the final proportions of each type of
offspring.
Interactions between Two Genes
• More than one gene can affect the same
trait. Lots of possible interactions: we will
look at a few, using only 2 genes and
complete dominance for both.
Two Genes
• 1. Two dominant alleles necessary for the trait.
Example: pea purple vs. white flowers. Mendel looked at
one gene, but there is another that is also necessary.
• Call the genes A and B. Both have two alleles: A and a,
B and b. To get a purple flower, the plant must have
both a A allele and a B allele.
• Selfing a double heterozygote Aa Bb gives 9/16 A_ B_,
3/16 A_ bb, 3/16 aa B_, and 1/16 aa bb. Only the 9/16
A_ B_ have both an A allele and a B allele: these are
purple. The rest are white.
• The final ratio is thus 9/16 purple to 7/16 white.
• Also worth noting: AA bb x aa BB is a cross between
two white plants. However, the offspring are all Aa Bb =
purple.
Two Genes
• 2. Duplicate genes. The
dominant allele from at least
one of the two genes is
needed to give the dominant
phenotype.
• Example: the plant "shepherd's
purse" (Capsella bursapastoris, in the mustard
family). To get a triangular
seed pod, you must have a
dominant allele from either the
A gene or the B gene. The
alternative is an ovoid seed
capsule.
• Thus, the offspring of a selfed
Aa Bb plant give 15/16
triangular (9/16 A_ B_, 3/16 A_
bb, 3/16 aa B_) and 1/16 ovoid
(aa bb).
Two Genes
• 3. Two genes with
different effects on the
trait. Chicken comb
types.
• Here we have: top left =
"pea" comb, from aa B_
genotype. Top right =
"rose comb", from A_ bb
genotype. Bottom left =
"single comb", from aa bb
genotype. Bottom right =
"walnut comb", from A_
B_ genotype.
Two Genes
• Epistasis: one gene controls the expression of another
gene.
• Example: albinism and coat color in dogs. An albino dog
lacks all pigment, so it is white. The albinism gene has
two alleles: C (normal color) and c (albino). Another
gene controls black vs. brown: B is the dominant black
allele, and b is the recessive brown allele.
• If two Bb Cc dogs are mated (both are black), 9/16 of the
offspring are B_ C_ (black), 3/16 are bb C_ (brown), and
4/16 are __ cc (white). The cc dogs can be BB, Bb, or
bb: it doesn't matter because the expression of the coat
color gene is controlled by the albino gene.
Penetrance and Expressivity
• Expression of many genes is affected by the
environment or by "background" genetic influences. Two
closely related concepts are used to describe this.
• Penetrance is the percentage of offspring with the
mutant genotype that express the mutant phenotype.
• Expressivity is the degree to which the mutant
phenotype is expressed.
• Example. Polydactyly is having extra fingers and toes.
There are several forms of this condition. For one form,
polydactyly is 65% penetrant: 65% of those who carry
the dominant polydactyly allele have extra digits.
Examining these people, there is a range of expression:
some have 1 extra digit, some have 2, etc. Also, some
of the digits are functional: have proper bones, muscles
and nerves, while others are missing vital components or
connections.
Polydactyly
• Antonio Alfonseca
"The Six Shooter",
former Chicago
Cubs relief pitcher.
• Six fingers and toes
on each hand, all
functional.
Environmental Effects
• Many traits are affected
by the environment as
well as by genetics.
• For example, the
hydrangea flower color is
controlled first by flower
color genes similar to
those in the pea: purple
vs. white with complete
dominance. But, pink vs.
purple is controlled by the
acidity of the soil in which
the plants grow.
Phenocopies
• A phenocopy is an organism that has a mutant
phenotype but a normal (wild type) genotype. It
got the mutant appearance through an
environmental cause.
• Drugs that cause birth defects are a common
cause. Nothing is genetically wrong with the
child, but it was exposed in utero to toxic
chemicals
• Another example: my cat Angel, whose tail got
run over by a car, looks like a Manx cat
(genetically tailless), even though she started
out with a normal tail.
The Sad Tail Tale
Pleiotropy
• Pleiotropy is one gene affecting
several traits. This is quite
common: genes make proteins
and often affect the overall
phenotype in subtle ways that
affect many different body
systems.
• Example: sickle cell anemia
causes enlarged spleen,
muscle pain, low red blood cell
count, resistance to malaria,
and early death. All of this is
caused by a single mutation in
one of the hemoglobin genes.