Sarah Margareta Ibrahim▯ Friday, January 11th 2013
BIOL 202 - Basic Genetics
Lecture 3 - Chromosomal Theory of Inheritance
Reading: Ch. 2 p.47-65
Left off last time with Mendel who did work ahead of its time and gave a presentation about it.
He wrote to the foremost authorities on hybridization at the time - a man by the name of Carl
Nageli but Nageli said that he was wrong and told people to work with the plant that he was
working with. The only problem was, the plant that he was working with was asexual and didnʼt
go through meiosis so it didnʼt get him very far. And then, Mendel just gave up on science.
People were still interested in science though and they studied the mechanisms of cells and the
behavior of chromosomes during meiosis. People began to think that he was right and so then
three scientists independently came up with these crosses and this 3:1 ratio - and then they
discovered Mendelʼs paper.
The Discovery of Sex Chromosomes
• Sex chromosomes were not known at the time that Mendel worked. The discovery due to a
careful series of observations by Nettie Stevens.
• Stevens worked with the mealworm. These mealworms also have sex chromosomes (theyʼre
actually beetles - the worm is the larva stage but you donʼt have to know mealworm life cycle)
• These sex chromosomes (X and Y) play a central role in
pinning down the connection between Mendelʼs factors and
• Thomas Hunt Morgan (from Columbia!) was a
developmental biologists and he needed an experimental
organism and he worked with fruit ﬂies. We work with these
a lot today (think: Hutt!) Why? Because they replicate quickly
(about 2 weeks) so you can grow many generations in a
year (more than peas), theyʼre well known organisms and
you can grow thousands of them very easily so you just give
them yeast and theyʼll live. Theyʼre also easy to cross.
• This was a wise choice as well because there are only four
pairs of chromosomes in the fruit ﬂy.
• Morgan was the ﬁrst one to establish a large genetics program
using fruit ﬂies.
• There is natural variation in fruit ﬂies. There is discrete
variation which is useful in genetics.
• One day, Morgan was looking in the lab and he discovered
something interesting. The normal eye type for fruit ﬂies was
red but he discovered one with a white eye (see the gross
picture to the right). So what did he do? He created pure
breading lines and then crossed them.
• Fruit ﬂies have an X and a Y. However, where it differs from
humans is that itʼs not the presence of Y that determines
whether itʼs a male or a female - itʼs the dosage of the X
chromosome. There are no sex determining factors on the Y
chromosomes. So a single X or XY would give you a male fruit
ﬂy. The female on the other hand has to have two Xʼs (XX).
▯ 1 Sarah Margareta Ibrahim▯ Friday, January 11th 2013
• So Morgan crossed these pure breeding line. He had a cross in which the parents were a pure
breeding red female (P1 Red) and a pure breeding white male
(P1 white). And in the F1 he got what you would expect if white
was recessive to red - everything was red regardless of the
• He expected (if this was simple type Mendelian Inheritance) to
ﬁnd this 3:1 ratio of red to white in the F2 when he crossed the
F1 - if this had been completely without regards to sex. But this
was not what he found. What he observed was 3:1 red to white
BUT the only ﬂies with white eyes were male. So he was on to
• He came up with an explanation that involved chromosomes to
explain this result and the connection between Mendelʼs factors
and chromosomes was made.
• So in the ﬁrst cross, he hypothesized that the red female was
homozygous for the wild type (obviously) and the male was
homozygous but it was linked to sex so the male had the X and
Y chromosome and on the X chromosome was this mutation
for white eyes. Why is there no mutation for white eyes on the
Y chromosome? Itʼs too small (see image on the right). Nettie
Stevens observed that the Y chromosomes tended to be small
so we expected them not to carry many genes. Then for the
male you have two types of gametes that can be produced and
of course the female can only produce a single type of gamete
(green cells in the second box). If you intercross the two red
cells (the F1 kids), you now see the 3:1 ratio is there and only
the white male had that chromosomal makeup.
• Heʼs made a connection between chromosomes and the
behavior of chromosomes in determining sex or gender and
the behavior of chromosomes in determining a phenotype
which has linked up those genes with those chromosomes.
▯ 2 Sarah Margareta Ibrahim▯ Friday, January 11th 2013
• So to test his hypothesis, he did a second cross which was
the reciprocal cross. He had a white female and red male both
with pure breeding lines.8
• He produced the F1 in this case and it behaved just as the
model would predict. You see a 1:1 segregation in the F1.
• Morgan used the term genes. There was however some
shred of doubt and it took one other experiment to drive home
the chromosomal theory.
• This discovery was made by Calvin Bridges - he worked in
Morganʼs lab and he discovered in this second cross and
exceptional result - just the opposite of what is in the image
on the right. Instead of seeing red females and white males,
he found just the opposite. He came up an explanation for
• What he hypothesized was that in the female, occasionally (about 1 out of 2000 times), thereʼs
something going wrong with meiosis. What happens is that the Xʼs fail to segregate into
different mitotic products and so you end up with an egg that has two Xʼs and the other egg is
missing a sex chromosome (itʼs not missing the other chromosomes, just the X). This is called
non-disjunction of chromosomes at meiosis.
• The two darker boxes (the female with three X chromosomes and the male with only one Y
chromosome) usually donʼt survive. So you end up with a red eyed male and a white eyed
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• You can go in and look at the chromosomes on them (in a microscope) and this is exactly what
• What to know: Know about sex-linked inheritance and why itʼs
important in the history of genetics (important in nailing down the
• Morgan was the ﬁrst North American to receive the nobel prize
for his work.
• In humans: We have what we call autosomes (non-sex