LS3-1_Lecture2H

LS3-1_Lecture2H - #2 The Molecular Nature of Genes 1.The...

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#2 The Molecular Nature of Genes 1.The nature of genetic material 2.DNA structure 3.Physicochemical properties of DNA 4.The size of DNA, genes, and genome
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Two dilemmas in “designing” a gene in evolution 1. Size vs stability Genes need to be small enough to fit into a tiny cell, but genes also need to be very accurately copied from generation to generation: e.g. with the estimated mutation frequency of less than one aa (amino acid) change per 200,000 years for a 400 aa protein. The dilemma is that the smaller the molecule the easier it is to undergo change or mutation. 2. Complexity vs simplicity Genetic materials need to be complex enough to specify all aspects of complex features and functions of a living organism (e.g. to study LS3), yet they need to be simple enough to be copied rapidly (e.g. <20 min in E. coli).
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Discovery of DNA DNA was first discovered by a biochemist Fredrich Miescher in 1869 in Germany. He isolated an acid and alkali-soluble material from white blood cells found in pus in surgical bandages. He found it contained some very large acidic molecule rich in phosphorus, and he called the material nuclein (now we know they are DNA-protrein mixture). The term “nucleic acid” was coined in 1889 by one of Miescher’s student Richard Altmann It took almost another half century for scientists to recognize the function and importance of DNA
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1. Experiments important for answering some fundamental questions in molecular biology Griffith experiment (1928) Avery-Macleod-McCarty experiment (1944) Hershey-Chase experiment (1952) These three experiments addressed the question: what was the genetic material ? Beadle-Tatum experiment (1941) Jacob et al experiment (1961) These two experiments addressed the question how does genetic information go from genes to proteins ?
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Griffith studied bacterium Streptococcus peneumoniae -The S strain causes pneumonia and it is lethal to mouse (virulent) -The R strain can be recognized by animal immune system, so it is avirulent. Question : why the difference? What did we know by the late 1920’s? 1. Genetic materials are located on chromosomes in the nucleus 2. Chromosomes are composed of DNA and proteins 3. The structure of proteins are much more complex than DNA 4. Although DNA was first suggested to be the genetic material by a botanist E. Zacharias in 1884, protein being genetic material was the prevailing view at the time S (virulent) R (avirulent) (1) Friedrich Griffith experiment (1928)
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a) virulent S strain bacteria infected and killed the host b) avirulent R strain did not infect the host c) Heat-killed S strain was no longer infectious or virulent d) When the avirulent R strain was mixed with heat-killed S strain, some R were “transformed” to become the virulent S strain! Griffith’s hypothesis: there was a “ S substance ” or transformation principle ” of the S strain. The S substance can be released by the dead S cells, which was taken up by R cell (avirulent) and transformed the R cell to the S cell (virulent).
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