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Chapter 15

by: Rachael Couch

Chapter 15 Biol 2311

Rachael Couch
GPA 3.9
Introduction to Biology
John Burr

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I am a TA for this class this year. Study my notes and you WILL do well!
Introduction to Biology
John Burr
Class Notes
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This 0 page Class Notes was uploaded by Rachael Couch on Thursday November 12, 2015. The Class Notes belongs to Biol 2311 at University of Texas at Dallas taught by John Burr in Fall 2014. Since its upload, it has received 22 views.


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Date Created: 11/12/15
Chapter 15 Genes Garrod 1902 I As early as 1902 Archibald Garrod proposed that some diseases might be caused by a hereditary defect in the ability to synthesize a particular enzyme in a metabolic pathway 0 In the disease alkaptonuria patients excrete large quantities of homogentisic acid in their urine turning it black 0 Garrod proposed that the enzyme that normally converts homogentisic acid to a different acid is missing in these patients 0 He called these genetic defects inborn errors of metabolism Beadle amp Tatum 1941 I 1941Beadle and Tatum stated their conclusion that genes code for proteins I In particular they proposed that genes code for the enzymes that catalyze the steps in a metabolic pathway 0 Their general approach to research was to make a gene defective and study the effect on the nowmutant organism 0 They studied common bread mold Neurospora crassa mutants that were defective in the synthesis of the amino acid arginine 0 They identified 3 classes of Arg mutants based on their ability or lack thereof to grow on minimal medium supplemented with one of the three intermediates in arginine biosynthesis I From this they deduced that each class of mutant was unable to carry out a different one of the three steps in the arginine pathway 3step synthesis I This was because each classed lacked the enzyme that catalyzed that step I Therefore they could conclude that Gene A the defect gene in class 1 arg mutants coded for Enzyme A the enzyme that the arg 1 mutants lacked while Gene B the defect gene in class 2 arg mutants coded for Enzyme B the enzyme that the class 2 arg mutants were missing etc I From this they concluded that each gene in an organism is responsible for making a different enzyme 0 This was often referred to as the one geneone enzyme hypothesis 0 Later broadened in the late 1940s to the one geneone protein hypothesis Nucleotide Sequence I Amino Acid Sequence 0 After Watson amp Crick discovered the DNA structure in 1953 the question about genes became How does the sequence of nucleotides in a DNA molecule direct the assembly of a sequence of amino acids in a protein 0 Early idea Amino acids directly interact with the nucleotides in the DNA molecule Crick proposed instead that the sequence of nucleotide bases in DNA act as some sort of code ie DNA was only an informationstorage molecule 195 8 Arthur Pardee working with Jacob amp Monod performed an experiment that used features of bacterial mating to study the regulation of gene expression 0 This was called the PaJaMo experiment and it provided the key to understanding the role of ribosome and mRNA in protein synthesis Brenner and Crick first realized that an implication of PaJaMo was that there must be a special kind of short lived RNA called messenger RNA that serves as a link between the DNA in the nucleus of a cell and the proteinsynthesizing ribosomes stable long lived RNA in the cytoplasm O Shortly thereafter Hurwitz amp Furth purified mRNA molecules and then went on to isolate the enzyme RNA polymerase that synthesizes mRNA molecules off a DNA template At this point it seemed likely that the sequence of bases in DNA was serving as a code for a sequence of amino acids and that mRNA molecules carried the code from the DNA to the ribosomes The next step was to decipher the code Deciphering Nucleotide Code George Gamow argued a priori that each amino acid is coded for by three nucleotides in the DNA 0 His argument was based off of the fact that at the time there were 20 known amino acids in proteins If each of the four different bases coded for one amino acid then there would only be 4 amino acids If it was a 2 base code there could be only 16 42 But with a 3 base code there could be 64 different amino acids 43 This hypothesis was proved experimentally by Crick and Brenner in 1961 by treating cells with pro avin which mimics a nucleotide pair and resulted in errors in DNA synthesis that lead to insertion of deletion of a nucleotide O Crick and Brenner were the first to realize that it caused insertion or deletion of a nucleotide and that this in turn could cause a reading frame shift I Consequently a nonsense sequence of amino acids would arise following the frameshift mutation and the protein would be completely inactive I A compensatory nucleotide subtraction or addition could then bring the reading frame back to its original order If this occurred soon enough after the original mutation the protein would be active Crick amp Brenner tested their ideas by taking advantage of a genetic system worked out by Benzer with a gene called the rII locus of the bacteriophage T4 0 The great advantage of this system was that many billions of individual phage progeny can be observed and even very rare mutations and rare recombinational events can be detected Crick amp Brenner realized that if the code was a triplet of nucleotides then a mutant gene with a single shift event could be corrected if recombined with other mutants each with a frame shift in the same direction which is what they observed I the triple mutants recovered the ability to encode a protein The next discovery Which bases code for which amino acids 0 Nirenberg amp Matthaei discovered that UUU is phenylalanine 0 Set up cellfree protein synthesizing system 0 Synthesized an RNA molecule that was just a string of Uridine residues polyU O The polyU in their proteinsynthesizing system formed a string of phenylalanine 0 Similarly CCCCC encoded protein ProProProPro so 0 CCC codes for Proline Pro 0 AAA codes for Lysine Lys and O GGG codes for Glycine Gly 0 This opened the door to a series of similar experiments 0 Final solution of the code Nirenberg and Leder found that one could use synthetic mRNA with just one trial trinucleotide codon at a time to ribosomes and the ribosomes would then bind the correct tRNA charged with its radiolabeled amino acid 0 The code was essentially all worked out in the next 5 years 0 The code is degenerate meaning that there is more than one codon for most amino acids ex CCC proline CCU CCA or CCG also proline 0 3 codons are nonsense or stop codon and one codon AUG is a start codon and codes for methionine 0 All proteins begin with the amino acid methionine Using the genetic code to predict an amino acid sequence The DNA sequence is transcribed as and translated as The Central Dogma 0 So by the end of the 1960s What was termed by Crick as the central dogma was well established DNA codes for mRNA and mRNA in turn codes for protein 0 The term transcription came to be used for the process of copying mRNA off of the DNA template 0 The term translation came to be used for the process of converting the information on mRNA into protein using ribosomes and tRNA 0 DNA sequences define the genotype proteins create the phenotype


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