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| Keywords: The fundamental difference between physical and “genetic” interactions. Topology of pathways. | |||||||
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Deliverables: Time management: Before you begin, estimate how long it will take you to complete this unit. Then, record in your course journal: the number of hours you estimated, the number of hours you worked on the unit, and the amount of time that passed between start and completion of this unit. Journal: Document your progress in your Course Journal. Some tasks may ask you to include specific items in your journal. Don’t overlook these. Insights: If you find something particularly noteworthy about this unit, make a note in your insights! page. |
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This unit discusses how “genetic interactions” are measured and can be used to infer pathway topologies.
Genetic interactions are very different from physicl interactions. Here the word interaction is used in an entirely different sense: it is not synonymous with contact it is synonymous with influence. In fact, most proteins that display genetic interactions would not be expected to interact physically as well. (Why? Think.) It is important not to mix up the two.
To understand what genetic interactions imply, think of the following analogy. If I were to break the wrist of my right arm, my survival would probably not be affected. My left arm would provide sufficient redundancy for most tasks. What about breaking the right index finger, or spraining the elbow as well? Painful, but functionally not much worse than breaking the wrist alone. What about indigestion, bunyons, cancer, or Alzheimers in addition to the fracture? Annoying, but really not significantly more so with or without a broken wrist. What about a broken left wrist? That would be bad. Losing the function of both hands is much, much worse than losing the function of only one hand. This is the kind of functional ordering that genetic interactions achieve: if two genes are active in the same system (like the right wrist and index finger) they will not display genetic interaction. The pathway is blocked and it matters little whether it is blocked in one or two points. If two genes work in completely different systems, they will also not show genetic interactions (like a fracture, combined with indigestion). Only if two genes affect parallel, mutually redundant pathways (left and right arm) will their joint deletion cause a critical situation for the affected organism. If the organism dies, we call this a synthetic lethal effect.
Genetic interactions can be observed in high-throughput experiments that systematically explore all pairs of gene-deletions in an organism, and the results provide insight how pathways can be topologically ordered according to shared objectives!
Task…
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