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Biology Chapter 15.docx

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McMaster University
Lovaye Kajiura

Biology Chapter 15: How Genes Work Bernard Ho November 13, 2010 What Genes Do − George Beadle and Edward Tatum studied how genes work − Beadle said, “one ought to be able to discover what genes do by making them defective” − The idea was to knock out a gene by damaging it and then infer what the gene does by observing the phenotype of the mutant individual − Today, alleles that do not function at all are called knock-out mutants, null mutants or loss-of-function mutants − Their experiments on N. crassa inspired their one-gene, one-enzyme hypothesis − They proposed that the mutant N. crassa individual could not make pyridoxine because it lacked an enzyme required to synthesize the compound and that the lack of enzyme was due to a genetic defect − Based on analyses of knock-out mutants, the one-gene, one-enzyme hypothesis claimed that genes contain the information needed to make proteins, many of which function as enzymes − Later work by Adrian Srb and Norman Horowitz on N. crassa supported the one- gene, one-enzyme hypothesis − Also showed that genes are responsible for all the different types of proteins produced by cells, not just enzymes The Central Dogma of Molecular Biology − The question was, how does a gene specify the production of a protein? − Given DNA’s structure, it appeared extremely unlikely that DNA directly catalyzed the reactions that produced proteins − Its shape was too regular to suggest that it could bind a wide variety of substrate molecules and lower the activation energy for chemical reactions − Instead, Crick proposed that the sequence of DNA might act as a code − The idea was that DNA was only an information-storage molecule − The instructions it contained would have to be read and then translated into proteins − Crick’s idea was that different combinations of bases could specify the 20 amino acids just as different combinations of dots and dashes specify the 26 letters of the alphabet − A particular stretch of DNA could then contain the information needed to specify the amino acid sequence of a particular enzyme − It soon became apparent, however, that the information encoded in the base sequence of DNA is not translated into the amino acid sequence of proteins directly − Instead, the link between DNA as information repository and proteins as cellular machines is indirect − RNA as the Intermediary between Genes and Proteins o DNA is enclosed within the nucleus o However, ribosomes, where protein synthesis takes place, are outside the nucleus, in the cytoplasm o Francois Jacob and Jacques Monod suggested that RNA molecules act as a link between genes and the protein-manufacturing centres o They predicted that short-lived molecules of RNA, called messenger RNA or mRNA, carry information from DNA to the site of protein synthesis o Follow-up research confirmed that the mRNA hypothesis is correct o One particular piece of evidence was the discovery of an enzyme that catalyzes the synthesis of RNA o This protein is called RNA polymerase because it polymerizes Ribonucleotides into strands of RNA o The key observation was that RNA polymerase synthesizes RNA molecules according to the information provided by the sequence of bases in a particular stretch of DNA o Unlike DNA polymerase, RNA polymerase does not require a primer to begin adding Ribonucleotides to a growing strand of RNA − The Central Dogma o The central dogma summarizes the flow of information in cells o It simply states that DNA codes for RNA, which codes for protein o DNA  RNA  proteins o DNA is the hereditary material o Genes consist of specific stretches of DNA that code for products used in the cell o The sequence of bases in DNA specifies the sequences of bases in an RNA molecule, which specifies the sequence of amino acids in a protein o In this way, genes ultimately code for proteins o Biologists used specialized vocabulary to summarize the sequence of events encapsulated in the central dogma o For example, biologists say that DNA is transcribed to RNA o In everyday English, the word transcription simply means making a copy of information o The scientific use of the term is appropriate because DNA acts as a permanent record, an archive or blueprint containing the information needed to build and run the cell o This permanent record is copied, via transcription, to the short-lived form called mRNA o The information is then transferred to a new molecular form, a sequence of amino acids o In everyday English, the word translation refers to the transferring of information from one language to another o In biology, the synthesis of protein from mRNA is called translation o Translation is the transferring of information from one type of molecule to another o DNA (information storage) (transcription) mRNA (information carrier) (translation) Proteins (active cell machinery) o According to the central dogma, an organism’s genotype is determined by the sequence of bases in its DNA while its phenotype is a product of the protein it produces o Later work revealed that alleles of the same gene differ in
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