Transcript Extensions to Mendelism • Mendel's pea experiments used a very simple genetic system: each gene had 2 alleles, one dominant and one recessive, and.

Extensions to Mendelism
• 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.
Partial (Incomplete) Dominance
• Mendel studied complete dominance: the
heterozygote looks exactly like the dominant
homozygote.
• 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. Antigens 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 codominant.
Electrophoresis
• When an organism's DNA or proteins are examined closely, almost
all genes are co-dominant. Both alleles of the gene are present,
even if they don't contribute equally to the phenotype.
• Electrophoresis is a way of separating the DNA of the genes or the
proteins the genes produce.
• Electrophoresis depends on a fundamental physical property:
charged objects 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, the enzyme "phosphatase" removes phosphate
groups from other molecules. When an extract is made of the
proteins in an organism, it is possible to separate the proteins by
electrophoresis and then stain the gel so only the phosphatase will
appear.
• In this example, there are 2 alleles of the gene that makes
phosphatase. One allele puts more negatively charged amino acids
on the protein's surface than the other allele does. Thus, one allele
produces a more highly charged protein that moves faster in
electrophoresis than the less charged protein from the other allele.
These two alleles are called F (Fast) and S (Slow).
• After electrophoresis and staining of the gel, an FF homozygote
shows a single band, far down the gel. The SS homozygote shows
a single band that has only moved a little ways down the gel. The
FS heterozygote shows both the F band and the S band. This
means that the phosphatase gene is co-dominant: the heterozygote
shows both parental types.
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 Mendels’ 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.
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
• Alfredo 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.
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.