ch11im - The Relationship Between Genes and Proteins

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The Relationship Between Genes and Proteins I. Archibald Garrod (Scottish physician, 1908) – reported that certain rare inherited diseases were caused by the absence of specific enzymes A. Alcaptonuria - urine gets dark upon exposure to air; they lack enzyme that oxidizes homogentisic acid 1. 2. B. He called such diseases inborn errors of metabolism - ignored for decades even though he had discovered connection between a genetic defect, a specific enzyme, and a specific metabolic condition II. George Beadle & Edward Tatum (Caltech, 1940s) – resurrected the idea that genes direct the production of enzymes A. Used Neurospora, a tropical bread mold, which grows in a very simple medium containing a single 1. It was presumed to make all its required metabolites & they reasoned that an organism with such broad synthetic capacity should be very sensitive to enzymatic deficiencies 2. These deficiencies should be easily detected with the right experimental protocol B. Beadle & Tatum's protocol – started with irradiation, which destroys the ability to make some enzymes & screen them for mutations that caused cells to lack a particular enzyme 1. Irradiate mold spores, creating individual cell populations with mutated genes 2. Screen them for mutation by growing spores on minimal medium that lacked essential compounds known to be synthesized by this organism (Neurospora) 3. If spore cannot grow in minimal medium, but can in medium supplemented with certain coenzyme (e.g., coenzyme A's pantothenic acid), it has enzymatic deficiency halting this compound's synthesis 4. Found specific metabolic deficiencies resulting from such enzyme deficiencies 5. Suggested that a gene carries the information for the construction of a particular enzyme C. 1. Two cells proved unable to grow on minimal medium: one needed pyridoxine (vitamin B 6 ) & the other needed thiamine (vitamin B 1 ) 2. 3. Each mutant had a gene defect causing enzyme deficiency, preventing cells from catalyzing a particular metabolic reaction —> clearly a gene carries information for making a particular enzyme D. This conclusion became known as the "one gene - one enzyme" hypothesis 1. Since enzymes often have >1 chain each of which is encoded by its own gene, the hypothesis was modified to one gene - one polypeptide hypothesis; still good approximation of basic gene function 2. One gene now shown to be able to be spliced differently to generate a variety of related polypeptides so one gene – one polypeptide hypothesis had to be modified III. Vernon Ingram (Cambridge Univ., 1956) - reported on molecular consequence of sickle cell anemia
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This note was uploaded on 09/10/2008 for the course BIO 201 taught by Professor Janicke during the Spring '08 term at SUNY Buffalo.

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ch11im - The Relationship Between Genes and Proteins

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