10 lecture - Epistatic interactions: ordering genes in a...

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Epistatic interactions: ordering genes in a signaling pathway As you have already seen, genes can be ordered based on the genetic interactions. Examples from the cell cycle in yeast and metabolic pathways in microorganisms show that in double mutants, the upstream gene in the pathway is epistatic to the downstream gene: the double mutant has the mutant phenotype of the upstream gene. When considering signaling pathways, the logic is reversed. The downstream gene is epistatic to the upstream gene. Let’s see why. We will consider examples in vulval development. In these cases, some cells will adopt one fate, the vulval fate, and other cells a different fate, the nonvulval fate. The signaling pathway, the EGF pathway in this case, promotes the vulval fate, and in its absence the nonvulval fate. Mutations can affect the pathway in one of two ways. They can disrupt a gene that is required for the pathway to function, eliminating pathway function in all cells and resulting in the vulvaless phenotype, or they can cause the pathway to be constitutively active in all cells, resulting in the multivulval phenotype.
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Positive regulation In a positive regulatory step, the product of one gene activates the product of a second gene. Let’s consider a generic example, where a signal turns on a pathway and this leads to a positive regulatory step. In this case, the signal activates gene 1, which activates gene 2, which then results in a particular phenotype because the pathway is on. Loss-of-function mutations in either of the two genes, 1 or 2, results in the same phenotype because the pathway is off, and making double mutants is not informative because the double mutant looks like a single mutant. For this type of pathway, sometimes gain-of-function mutations can be used to order genes. In the example below, and activating mutation in gene to causes the pathway to be on, and results in a unique phenotype whether gene 1 is wild-type or mutant: the double mutant, gene 1 loss-of- function, gene 2 gain-of-function, has the gene 2 gain-of-function
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This note was uploaded on 09/03/2010 for the course MCB 104 taught by Professor Urnov during the Spring '09 term at University of California, Berkeley.

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10 lecture - Epistatic interactions: ordering genes in a...

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