BIL 104 - Lecture 6

GENE INTERACTIONS Many people studying genetics for the first time have a tendency to "forget" that we study the inheritance of one trait in a set of offspring (hair color, eye color, hemophilia, color blindness, etc.), there are literally thousands of other genes separating, segregating and assorting along with the gene you happen to be examining.

In fact, MOST phentypic traits are produced by the interaction of more than one gene, and the effect of the environment on the expression of those genes can complicate things even more.

And of course, we have terminology for these phenomena.
And of course, you have to learn it.

PLEIOTROPY - a single gene affects the phenotype of more than one different character.

Example: Albinism.
A single defect in one of the enzymes catalyzing tyrosine (through many intermediate products) to melanin can affect multiple phenotypic characters, from eye color to skin color to hair color.
Another Example - Sickle Cell Anemia
The mutation which changes the 6th amino acid from the terminal end of the Beta-protein chain is changed from glutamate to valine, making the chain hydrophobic rather than hydrophilic. Because the mutant hemoglobin precipitates readily in slightly acid conditions (as when the sufferer undergoes physical exertion, dissolving CO2 in the blood), and the malformed rbc's clog the capillaries, causing multiple phenotypic problems:
- malformed rbc's
- slowed blood flow due to malformed rbc's
- "tower skull" phenotype due to hypertrophy of red marrow in the cranium
- stunted growth
Recall the silver lining, however:
There's a silver lining to every cloud...
Homozygous normal people have a high incidence of malaria, which can be fatal.
Homozygous recessive sickle cell sufferers die of the fatal anemia, but do not contract malaria.
Heterozygotes suffer neither the symptoms of sickle cell anemia NOR contract malaria, as the abnormal blood cells somehow make an inhospitable environment for the protozoan parasite, Plasmodium
This is one form of HETEROZYGOTE ADVANTAGE.

EPISTASIS - Multiple genes, each with more than one allele, interact to produce unexpected phenotypes.

Example: Inheritance of comb shape in chickens
- Rose gene: R or r
- Pea gene: P or p
  - Rose gene, if present in RR or Rr will produce a "rose type" comb-- but ONLY if Pea gene is present in pp condition.
  - Pea gene, if present in PP or Pp will produce a "pea type" comb-- but ONLY if Rose gene is present in rr condition.
  - If one dominant allele is present for BOTH pea and rose, a "walnut type" comb results. R_P_ will give "walnut" comb.
  - If both alleles are present in double recessive condition, (rrpp), the WILD TYPE, single comb results.

POLYGENIC TRAIT - the expression of a single phenotypic trait is affected by the action of more than one gene.

There are too many examples to list, since most traits (beyond the expression of an enzyme itself) are, at least to some degree, polygenic.

One cute example is the inheritance of fruit color in bell peppers. There are at least three genes involved here:

Y - timing of chlorophyll elimination (Y - early; y - normal)
R - color of carotenoids (R - red; r - yellow)
C - regulation of carotenoid deposition (C - normal; c1, c2 - lowered concentration)
This leads to a few possible genotypes producing interesting phenotypes:
- Y- rr c1c2 - pale yellow
- Y- rr Cc2 - darker yellow
- yy rr CC - green
- Y- R- CC - red
- yy Rr CC - purple
- Y- Rr Cc2 - pale yellow

Sometimes, the alleles of a single gene can interact in ways that result in phenotypic ratios in offspring that are not predicted by Mendel's Laws. Two such phenomena, not to be confused with one another are

INCOMPLETE DOMINANCE and

CODOMINANCE

In INCOMPLETE DOMINANCE the two alleles both produce proteins, but one is non-functional. This results in heterozygotes producing only half the amount of protein produced by a homozygous dominant individual.

Mirabilis jalapa

There are two alleles of a gene for flower petal color.

R1: red pigment produced
R2: no pigment produced
R1R1: red petals
R2R2: white flowers
R1R2: pink flowers

The wild type R1 allele codes for an enzyme vital for the conversion of the precursor in the flower into the xanthophyll pigment.

The mutant R2 allele produces an enzyme incapable of catalyzing the reaction.

This recalls the importance of Inborn Errors of Metabolism:

normal (wild type) allele - functional enzyme
mutant allele - nonfunctional enzyme

Another example of incomplete dominance: Tay Sachs disease in humans.

HEXOSAMINIDASE-A is responsible for breaking down lipids. In its absence, sphingolipids accumulate in the developing brain and peripheral nervous system of affected fetuses/young children

Result: brain damage, retardation, death by age five.

TT: normal
Tt: half the amount of enzyme produced, but sufficient for normal development
tt: no functional enzyme; expression of Tay Sachs disease.
This is Incomplete Dominance because both alleles are expressed (i.e., a protein is made from each allele), but only one is functional.

In CODOMINANCE, both alleles are expressed, and both products are functional, though they may be different.

If you know anything about human blood types, then you probably know...

People with blood type AB are universal recipients
People with blood type A are can receive from type A or type O
People with blood type B are can receive from type B or type O
People with blood type O are universal donors

Ever wonder why? (Too bad. I'm going to tell you anyway.)

An ANTIBODY is a substance produced by an organism's immune system that helps it to fight invasion by a foreign object, such as a virus, bacterium or proteins from another organism (either of the same species or different species).

An ANTIGEN is any foreign substance that causes an immune response in an individual organism.

This means that what's an antigen to me might not be an antigen to you! For example, your body recognizes its own proteins and under normal circumstances will never mount an immune system attack against them. However, if you are exposed to foreign proteins (or to a virus or bacterium or other pathogen that your body doesn't recognize as "self"--then the immune system attacks!

Our genes tell us to insert certain proteins into the plasma membranes of particular cells, and because each of us has different genes, those proteins vary from individual to individual.

FOR EXAMPLE...

Humans with type AB blood have two different immunoglobins (I^A and I^B) inserted into the blood cell membrane.
Humans with type A blood have only I^A immunoglobin.
Humans with type B blood have only I^B immunoglobin.
Humans with type O blood have neither I^A nor I^B immunoglobin.

The A & B alleles operate by modifying the wild type (type O) mucopolysaccharide terminal sugars on the ABO immunoglobin protein inserted into the plasma membrane of all red blood cells.

type O:

fucose--galactose--N-acetylglucosamine (glunac)...

type A individuals have a modified enzyme (alpha-3-N-acetyl-D-galactosaminyl transferase), which modifies the terminal sugars like so:

type B individuals produce alpha-3-D galactosyl tranferase, which modifies the terminal sugars of the "o" type like so::

Because the immune system of people with type AB immunoglobins recognizes both I^A and I^B as "self", they don't produce antibodies against them. They can receive blood of any other type (A, B, or O)

But people with type A blood LACK I^B. Therefore, their bodies recognize I^B as "foreign" and launch an immune system attack if any cells with I^B enter the body. This results in blood clotting and other problems.

The same thing is true in reverse for people with type B blood. They lack I^A, and so recognize it as "foreign" and attack it.

Type O people have neither I^A nor I^B on their red blood cells, so if they are exposed to I^A nor I^B, their immune system recognizes it as foreign, and mounts an attack. Therefore, type O people can receive blood only from type O individuals.

NOTE: Antibodies to a particular antigen are usually not present at all times, nor are they present in large quantities in the blood unless the blood has recently been exposed to a SENSITIZING AGENT (an antigen that elicits an immune response).
So even if a type AB person receives blood from a type O person (who is able to manufacture antibodies against both I^A and I^B), there may be one or two A or B antibodies floating around in the donated blood, but without the type O immune system to back it up, these won't cause any lasting harm.

A summary of ABO blood types and genotypes...

blood phenotype	antigens on RBC	plasma antibodies	possible genotypes	can receive blood type(s)
A	A	anti-B	IAIA; IAio
B	B	anti-A	IBIB; IBio
AB	AB	none	IAIB
o	none	anti-A, anti-B	ioio