Lecture 6- the genetic code

Lecture 6- the genetic code - From the structure of the...

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From the structure of the DNA, as deduced by Watson and Crick, it seemed clear that the genetic information must be encoded in the sequence of the nucleotide pairs that form the ladder rungs of the double helix. The trick was to crack the code. But to do that, one had to first know what the code was coding for. It obviously was not an encoded message in english (or any other language) saying "make a person with red hair". So what is it saying? The code is telling the cell what proteins to make. The first evidence for this conclusion came from Garrod. He studied patients with alkaptonuria, a disease that, in addition to causing arthritis, makes your urine turn black when exposed to air. He proposed that alkaptouria is hereditary and that it is autosomal recessive. More importantly though, he proposed that the problem was an "inborn error of metabolism" caused by the absence of an enzyme that metabolizes tyrosine. It was eventually found the genetic error results in the specific loss of one enzyme (homogentisate 1,2 dioxygenase (HGD)).
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However, it was Beadle and Tatum that really clarified the relationship between genotype and phenotype. Working with the mold Neurospora, they isolated mutants that required certain metabolic precursors in order to grow. These mutants were called auxotrophs as opposed to the wild type prototrophs. The reason these mutants couldn't grow was because they lacked enzymes that were part of a metabolic pathway. Therefore, the mutants had to be fed the metabolite that they couldn't make for themselves. In a sense, these metabolites became like vitamins for the mutants. By looking at what precursors the
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different mutants required in order to grow, they were able to deduce what enzyme in the metabolic pathway each of the mutants was missing. This led to the one-gene, one enzyme hypothesis (which has been modified to the one- gene, one-protein hypothesis since some enzymes have more than one protein component and some proteins aren't enzymes) About this time Fred Sanger determined the first peptide sequence of a protein, insulin. Clearly the unique properties of a protein were determined by its unique amino acid
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Lecture 6- the genetic code - From the structure of the...

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