Lecture 9: Human Genetics | Video Lectures | Introduction …

I want to go back a second to the end of last time because in the closing moments there, we, or at least I, got a little bit lost, and where the plusses and minuses were at a certain table.

And, I want to go back and make sure we've got that straight.

We were talking about a situation where we were trying to use genetics, and the phenotypes that might be observed in mutants to try to understand the biochemical pathway because we're beginning to try to unite the geneticist's point of view who looks only at mutants, and the biochemist's point of view who looks at pathways and proteins. And, I had hypothesized that there was some biochemists who had thought up a possible pathway for the synthesis of arginine that involved some precursor, alpha, beta, gamma, where alpha is turned into beta; beta is turned into gamma; and gamma is used to turn into arginine.

And, hypothetically, there would be some enzymes: enzyme A that converts alpha, enzyme B that converts beta, and enzyme C that converts gamma. And, we were just thinking about, what would the phenotypes look like of different arginine auxotrophs that had blocks at different stages in the pathway. If I had an arginine auxotroph that had a block here because let's say a mutation in a gene affecting this enzyme, or at a block here at a mutation affecting, say, the gene that encodes enzyme C, how would I be able to tell very simply that they were in different genes? Last time, we found that we could tell they were in different genes by doing a cross between a mutant that had the first mutation, and a mutant that had the second mutation, and looking at the double heterozygote, right? And, if in the double heterozygote you had a wild type or a normal phenotype, then they had to be in different genes, OK? Remember that?

That was called a test of complementation. That was how we were able to sort out which mutations were in the same gene, and which mutations were in different genes. Now we can go a step further. When we've established that they're in different genes, we can try to begin to think, how do these genes relate to a biochemical pathway? I wanted to begin to introduce, because it'll be relevant for today, this notion: so, suppose I had a mutation that affected enzyme A so that this enzymatic step couldn't be carried out.

Such a mutant, when I just try to grow it on minimal medium won't be able to grow. If I give it the substrate alpha, it doesn't do it any good because it hasn't got the enzyme to convert alpha. So, given alpha, it won't grow. But if I give it beta, what will happen? It can grow because I've bypassed the defect. What about if I give it gamma? Arginine?

Now, if instead the mutation were affecting enzymatic step here, then if I give it on minimal it won't grow, alpha won't suffice. If I give it beta, it won't suffice. If I give it gamma, however, I've bypassed the defect and it will grow. So, that's a very different phenotype. The ability tor grow, here, given beta, in this strain here. The inability to grow, this has an inability to grow on beta, but it can grow on gamma. What about this last line?

If I have a mutation and the last enzymatic step, minimal medium can't grow with alpha, can't grow with beta, can't even grow with gamma. But, it can grow with arginine because I've bypassed that step. So, I get a different phenotype, the inability to grow even on gamma, but I can grow on arginine. Now, here, if I put together those mutants and make a double mutant, a double homozygote, let's say, that's defective in both A and B, which will it look like? Will it be able to grow on minimal medium? Will it be able to grow on alpha? Will it be able to grow on beta?

Will it be able to grow on gamma and arginine? What about if I have a double mutant in B and C, minus, minus, minus, minus, plus? So this looks the same as that. This looks the same as that. And so, by looking at different mutant combinations, I can see that the phenotype of B here is what occurs in the double mutant. So, this phenotype is epistatic to this phenotype.

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Lecture 9: Human Genetics | Video Lectures | Introduction ...