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Lecture 3

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McGill University
Biology (Sci)
BIOL 202
Daniel Schoen

Sarah Margareta Ibrahim▯ Friday, January 11th 2013 BIOL 202 - Basic Genetics Lecture 3 - Chromosomal Theory of Inheritance Reading: Ch. 2 p.47-65 Quick Recap 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 chromosomes. • 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 sex. • 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 something. • 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 this: • 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 female. ▯ 3 Sarah Margareta Ibrahim▯ Friday, January 11th 2013 • You can go in and look at the chromosomes on them (in a microscope) and this is exactly what you see. • What to know: Know about sex-linked inheritance and why itʼs important in the history of genetics (important in nailing down the chromosomal theory) • Morgan was the first North American to receive the nobel prize for his work. • In humans: We have what we call autosomes (non-sex chromosomes) and
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