Download Mendelian genetics At the beginning of the last section, we

Mendelian genetics
At the beginning of the last section, we mentioned that while you may resemble your parents, you're
not an exact copy.
Knowing what we do about mitosis and meiosis, we're now ready to figure this out.
Inheritance has a long history. The ancient Greeks were some of the first to give it serious thought;
they has some interesting ideas (e.g., “blending), but it wasn't until the mid 1800's that real progress
was made.
Gregor Mendel
An Augustinian Monk working in Austria (today part of the Czech Republic).
Had training in chemistry, physics & mathematics.
Worked with garden peas to deduce how inheritance worked.
Was experienced with these from childhood - AND he could control their breeding
(i.e., which plant bred with which).
Picked seven characteristics of pea plants to study how these characteristics were passed on
from one generation to the next [OVERHEAD, fig. 9.2D, p. 155].
Started with pure breeding strains of plants
For example, made sure he started with a plant that only produced purple flowers
though several generations.
Started by hybridizing these pure-bred strains.
For example, what would happen if he crossed a plant that produced purple flowers
with one that produced white flowers?
Some terminology:
P - parent generation
F1 - first offspring generation
F2 - offspring from F1
etc.
Single characteristics (in pea plants) [OVERHEAD, fig. 9.3A, p. 156]:
Starting with plants that only produced purple flowers (pure strain purple) and plants that only
produced white flowers (pure strain white):
Mendel discovered that the F1 generation was all purple (notice we're not saying they
were a pure strain of purple).
What happened to white? Notice also that Mendel disproved the “blending”
hypothesis that some people were considering (as far back as the Greeks).
Mendel took the F1 generation and bred it with itself (i.e., crossed plants from F1 with other
plants from F1).
Result was F2, but in F2, approximately ¾ of the flowers were purple, and ¼ were
white.
What was going on? Where did white suddenly come from?
This should be no surprise - some of the characteristics about you may quite possibly
come from your grand parents, and not your parents.
Nevertheless, what's happening?
Mendel developed four hypotheses based on his research.
Mendel's four hypotheses:
1) There are alternative forms of “heritable factors” (what we now call genes).
Alternative forms are called alleles. In our flowers we have two alleles for color,
purple and white.
2) Each individual inherits two copies of these alleles. These may be two of the same
(e.g., two alleles for purple), or two different ones (one for white, one for purple).
If an individual has two of the same alleles, it is termed “homozygous”
If an individual has two different alleles, it is “heterozygous”.
3) If the two alleles are different (the individual is a heterozygote), then one of the
alleles will determine the individual's appearance. This is the "dominant" allele.
The other allele essentially has no effect on the individual, and is called
“recessive”.
Note that this hypothesis is not always true (more later).
4) a gamete (sperm or egg) carries only 1 allele for each trait (because alleles separate
from each other during production of gametes (meiosis)).
Sometimes known as the law of segregation.
When gametes come together (fertilization), there are again two copies of each
allele.
Mendel's explanation of the observed events [OVERHEAD, fig. 9.3B, p. 156]:
Using Mendel's first two hypotheses, we can say:
One of the parent flowers (P plants) has two purple alleles,
The other has two white alleles
Thus, the gametes from the P generation are either P (purple) or p (white).
(Note that unfortunately your text uses P for both the “P” generation and
the P (purple) allele - they mean two different things).
All the offspring from the parents got one P (purple) and one p (white).
Putting these together, we use hypothesis 3 and conclude that the reason all the
F1 plants are purple is due to the fact that P (purple) is dominant.
p (white) is recessive.
When looking at two alleles where one is dominant and the other
recessive, we often use capital letters for the dominant allele, and lower
case letters for the recessive.
Finally, we can also explain the F2 generation. We know that all the F1 generation must
have one P and one p (they're all Pp). Half of the sperm from F1 will be P, half p.
Similarly, half of the eggs will be P, and half p.
If we now combine eggs and sperm, we can get four possible results:
Egg with P and sperm with p (Result = Pp)
Egg with P and sperm with P (Result = PP)
Egg with p and sperm with p (Result = pp)
Egg with p and sperm with P (Result = Pp)
The Punnett square illustrates a better way of doing this (we put all possible
sperms on one side, and all possible eggs on the other)
I either case, notice we now have:
¾ purple (both PP and Pp are purple), and ¼ white (pp)
Tis finally explains Mendel's results for F2.
Notice that the phenotypes and genotypes are different [OVERHEAD, not in book].
Phenotype - the physical appearance of our organism
(Due to genetic AND environmental effects, though we won't worry too
much about environmental effects right now).
Our phenotype ratio is 3 purple : 1 white (¾ purple, ¼ white).
Genotype - the genetic makeup of our organism
Our genotype ratio is 1 PP : 2 Pp : 1 pp (or ¼ PP, ½ Pp, ¼ pp).
Mendel noticed that all of his other characteristics also worked the same way.
Incidentally, statisticians have proved that Mendel cheated a little with his
results.
His results were better than one would expect (his ratios were way too
good).
Nevertheless, he had the right ideas, and interpreted his data correctly
(he just made it look a little better).
Some final remarks on Mendel:
He published his results, which were promptly forgotten (Darwin had a copy,
but didn't know what to do with it).
He tried some crosses with animals (bees), but had difficulty controlling the
crosses.
Eventually he was elected abbot, and after that spent most of his time
administrating the monastery.
Mendel's research was eventually re-discovered and acknowledged about the
turn of the century (1900).
Review of gene loci [OVERHEAD, fig. 9.4, p. 157]
Where are these alleles? Alleles for a particular trait are at the same loci on homologous
chromosomes.
Remember that during meiosis I, our homologous chromosomes go their separate
ways, so our alleles go their separate ways (which is why Mendel's hypothesis 4
works).
Working with more than one trait at a time [OVERHEAD, fig. 9.5A, p. 158].
Often, when we look at more than one trait, it turns out these traits are on different
chromosomes (not homologous pairs). For example:
Seed color (yellow and green) and seed shape (round and wrinkled)
Y (yellow) is dominant, and R (round) is dominant (Mendel deduced this from
previous crosses).
So if we now take an individual that's homozygous for yellow and round
(YYRR) and cross with an individual that's homozygous for green and
wrinkled (yyrr), as expected, all the offspring are:
YyRr (yellow and round).
The question becomes, what happens when we cross this F1 generation with
itself (YyRr x YyRr)?
Two possible results. If Y and R always go together, and y and r always
go together, we expect the results on the left hand side of the figure.
(Four possible genotypes, two possible phenotypes)
On the other hand, if Y and R each do their own thing (Y doesn't care
what R is doing and vice versa), we get the result on the right hand side
of the figure. (Nine possible genotypes, four possible phenotypes).
The results were consistent with the second hypothesis. Thus we have the “law
of independent assortment”.
This states that each pair of alleles segregates (separates) independently
of every other pair [OVERHEAD, fig. 9.16, p. 171].
(For some silly reason your text puts this figure no where near
the previous one).
As it turns out, this is only true if the traits are on different
chromosomes (i.e., on non-homologous chromosomes).
There are situations where this obviously doesn't hold. (Not all
traits are independent).
Remember - this is why we get many different combinations of chromosomes
in our gametes (fig. 9.16).
Another example is coat color in Labrador retrievers [OVERHEAD, fig. 9.5B, p. 159]
Testcrosses:
How can we find out if someone is PP (purple) or Pp (also purple)?
A testcross can be used. Cross the individual with a homozygous recessive:
If the individual is PP, all offspring will be purple (why?)
If the individual is Pp, ½ of the offspring will be purple, the other half yellow.
[OVERHEAD, fig. 9.6, p. 159] uses our labs as an example.
Probability:
Be aware that most of what we're doing can be modeled using the laws of probability.
I would love to go through this material (I'm a statistician after all!), but I don't see how it
adds much to the discussion.
Most of the problems here or in lab can be solved using Punnett squares & logic.
Human genetic traits:
[OVERHEAD, fig. 9.8A, p. 161]
Freckles / no freckles
Widow's peak / no widow's peak
Free earlobe / attached earlobe
Important: notice that a dominant trait does NOT mean it's more common (Purple
kernels are dominant in corn - how much purple corn is there?)
More on this soon (when we do Hardy-Weinberg).
Some of these human traits can be diseases (this topic also introduces “family trees”) [OVERHEAD,
not in book]
A deaf boy was born to two normal parents. Deaf is recessive (in this kind of deafness)
[OVERHEAD, fig. 9.9A, p. 162].
Implies that both parents were heterozygous (only in that way could Jonathan have inherited
two recessive alleles).
Also, notice that Jonathan had deaf children. He only passed on ONE allele for deafness.
The other must have come from his wife.
Implies that one of his wife's parents must have been heterozygous, but we can't say
which one.
Many genetic diseases are caused by a single gene (and one defective allele).
[OVERHEAD, table 9.9, p. 163]
Most serious genetic diseases are recessive
If a genetic disease is dominant, it usually is not passed on to the offspring.
Children die before being able to pass on the disease, so the disease
does not “survive”.
Recessive diseases can be carried without ill effects by heterozygotes. These
are often termed “carriers”.
But some dominant genetic diseases exist:
Huntington's disease
Does not strike until middle age. The parents have already had children,
so the disease can be passed on.
Inbreeding often increases the incidence of the disease
Briefly, related individuals are more likely to both be carriers, and so pass on
the disease to their children.
This is easy to see with siblings, but even with 1st or 2nd cousins, the
probability is still higher than normal. One can actually calculate this
using some of the probability we skipped over.
Expansions / variations on Mendel.
Mendel's hypotheses and laws do not account for everything. Some common exceptions:
Incomplete dominance
In this case, neither allele is “dominant”. The individual has traits “in between” the
two alleles.
The result is often a “blending” of the characteristics of both parents.
[OVERHEAD, fig. 9.11A, p. 166]
Flowers are red, white, or pink.
BUT, in F2, we get back to pure white or red, which wouldn't happen if the old
“blending” hypothesis were correct.
Blending pink and pink should yield just more pink.
Hypercholesterolemia is another example
HH -> normal
Hh -> cholesterol levels about twice normal
hh -> very high cholesterol levels.
There is also co-dominance, where both alleles are expressed - the difference between this and
incomplete dominance is subtle.
Co-dominance means both alleles are expressed (the result is not “in between”).
Blood groups are an example.
A and B are both expressed - blood type AB is not a “mix” of types A and B.
More than two alleles and more on blood types and co-dominance:
Many traits can have more than two alleles. Blood groups are a good example. There
are three alleles:
Type A, type B, and type O.
Types A and B are dominant to type O:
AO & AA are essentially the same
BO and BB are essentially the same
OO is the only way to be type O
Types A & B are co-dominant.
People have some blood cells with type A characteristics, and some
blood cells with type B characteristics.
Note that AB is not a “blending” of types A and B.
The reason one has to be careful with blood transfusions [OVERHEAD, fig.
9.12, p. 167]:
Types A have cell identifiers for type A. Type B has different cell
identifiers and is attacked.
The same goes for type B (type A cells are attacked).
In type AB, the body knows about both types of cells, so neither is
attacked.
Type O has no cell identifiers, so type O can be given to anybody
(types A, B, or AB do not recognize O (no identifiers), and do not
attack it).
On the other hand, type O individuals will recognize both types A and
B as foreign (type O individuals don't recognize any cell identifiers, so
all cell identifiers are considered foreign).
O is the universal donor, AB the universal recpipient.
This presentation is just a little different than the book, but they both wind up
in the same place (the book might be marginally more accurate, this might be a
little easier to understand).
Pleiotropy
Simply put, this is where one allele will have multiple effects.
[OVERHEAD, fig. 9.13, p. 168]
Sickle cell anemia is a good example.
Notice that this (as mentioned) is also an example of incomplete dominance.
Heterozygotes are generally normal but much more resistant to malaria. Their cells
will sickle under poor oxygen conditions, or when attacked by the malaria parasite
(and the infected cells get destroyed!).
Homozygous individuals either:
Don't get sickle cell (but get malaria)
Get sickle cell (which is often fatal)
We may mention this again when we do evolution, but being heterozygote is a distinct
advantage.
Malaria kills 2/3 of a million people every year.
It's a strange situation, since both homozygote conditions are at a disadvantage.
Many genes can influence a single character (kind of the opposite of pleiotropy).
[OVERHEAD, fig. 9.14, p. 169]
Three genes all contribute to skin color (book mentions it's at least three, maybe more).
Dominant in each case contributes some pigment.
We can go from 0 to 6 (7 levels) of pigment.
Environmental influences:
Environmental influences can determine a lot about our appearance
Exercise, diet, altitude, sunlight, etc.
(Mendel used characteristics that were generally not influenced by the environment).
Genetic testing:
There are many tests that can determine if some of these genetic diseases are present.
Specific disease causing alleles can be detected.
Depending on what is found, a couple may decide not to have children, for example (if
both parents are carriers for a nasty disease).
We need to be careful we don't use this information to make decisions about getting
life insurance, etc.
See also section 9.10 for more on genetic testing and some of the ethical issues raised.
Exceptions to the law of independent assortment
If the genes we are considering are on the same chromosomes, then “independent assortment”
may not work as Mendel described.
[OVERHEAD, fig. 9.17, p. 172]
Purple and long pollen are on the same chromosome.
Crossing PpLl x PpLl did not yield the expected ratio of 9:3:3:1
Instead we got “almost” our 3:1 ratio of 3 purple-long: 1 red-round.
P and L are on the same chromosome, and p and l are on the same
chromosome, so we get 3 dominant : 1 recessive (a “typical” monohybrid
cross).
These are also known as “linked” genes.
Crossing over produced the few exceptions to our 3:1 ratio.
Review: [OVERHEAD, fig. 9.18A, p. 173]
Crossing over was first hypothesized working with fruit flies:
[OVERHEAD, fig. 9.18C, p. 173]
A fly that was known to be heterozygous for two different traits (body color
and wing length) was crossed with a fly recessive for both traits (black body
and vestigial wings).
A dihybrid cross in which the genes are on different chromosomes
(independent assortment) would produce a 1:1:1:1 ratio:
¼ gray, normal, ¼ gray, vestigial, ¼ black, normal, ¼ black,
vestigial.
Instead, most (but not all!) of the flies were “gray, normal” or “black,
vestigial”.
The hypothesis was developed that these genes are linked (i.e.
on the same chromosome), but that “some mechanism”
sometimes broke the linkage to produce the other two varieties.
This “some mechanism” was later shown to be crossing
over.
It turns out, crossing over can be used to identify the location of genes (to “map” genes).
The further apart to genes (on the same chromosome) are, the more likely it is that
they will undergo crossing over.
If two genes are far apart, there are many points between them where crossing
over can occur.
If two genes are close together, there are only a few points between them
where crossing over can occur.
Incidentally, all points on a chromosome are not “equally” likely to be
involved in crossing over, but the general principle holds. The greater the
distance, the more likely crossing over will occur between genes.
So, by looking at how often genes recombine through crossing over, we can get an
idea of how far genes are physically apart on the chromosome.
[OVERHEAD, fig. 9.19 A & B, p. 174].
Sex and chromosomes
As described, for many animals, chromosomes determine sex. In humans, we use X and Y
(named due to the shape of the chromosomes).
XY -> male, XX -> female [OVERHEAD, fig. 9.20 B - E, p. 175].
A gene on the Y chromosome codes for the development of testes.
The exact process is not yet understood,
Other systems:
XX -> female, XO -> male (where O means “no” chromosome)
Found in some insects like grasshoppers.
Note that in both the XY and XO systems it's the male that determines sex:
Sperm can be either X or Y (humans), or X or O (some insects like
grasshoppers).
ZW -> female, ZZ -> male
In some birds, fish, butterflies.
Notice that it is the female that has two different chromosomes.
Therefore, it's the female that determines sex:
Eggs can be either Z or W, males can only make sperm with Z.
Some insects use chromosome number:
diploid --> female, haploid --> male
Some animals (some turtles, crocodiles) have temperature determined sex:
The temperature of their eggs determines if the individual will be male
or female.
There is lots of variation in determining sex.
And, of course, many organisms are hermaphrodites (have male and
female parts); for them this is irrelevant.
Sex linked traits
If genes (alleles) are being carried on the sex chromosomes, strange things can
happen.
In humans, for example, the Y chromosome does not carry many genes. So if
genetic information is being carried on the sex chromosomes, men get only one
allele (from the X chromosome).
Genes carried on the sex chromosomes are often referred to as sex linked.
Let's take a look to see what can happen. We'll look at fruit flies (again).
White eyes is a recessive trait.
Further, it's carried on the sex chromosomes (fruit flies have a XY system for
determining sex).
We have:
XR XR -> red female
XR Xr -> red female
Xr Xr -> white female
XR Y -> red male (notice males only have one allele)
Xr Y
-> white male
As you might expect, it's easier to get white males than white females.
Three examples [OVERHEAD, fig. 9.21 B - D, p. 176]:
Crossing XR XR with Xr Y:
½ XR Xr, ½ XR Y
(All males must get XR from the mother)
Crossing XR Xr with XR Y
¼ XR XR, ¼ XR Y, ¼ Xr XR, ¼ Xr Y
(Notice that only males can be white, for a female to be white,
she MUST get Xr from the father (the father does not have Xr)).
Crossing XR Xr with Xr Y
¼ XR Xr, ¼ XR Y, ¼ Xr Xr, ¼ Xr Y
(This time, the female offspring can get one Xr from the mother
and one Xr from the father, so we do get white females).
Due to this phenomenon, sex linked recessive traits show up more commonly in males
than in females (males only need one recessive allele, females need two).
If this trait is also a disease, this can have devastating consequences for males
(they're more likely to get the disease).
Red-green color blindness is more common in men
One type of hemophilia is more common in men
[OVERHEAD, fig. 9.22, p. 177]
Duchenne muscular dystrophy is more common in men
A disease that causes muscle weakening and loss of
coordination. Often fatal by the early 20's (in age).
All three diseases are more common in men because all three are carried on the
sex chromosome (the X chromosome, not the Y).