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GENETICS 603 Outline and Key Topics for Lecture 1 DNA Genes are made of DNA 1928 Griffith showed that a mixture of heat-killed SIII (smooth, virulent) Pnuemcoccal bacteria and live RII (rough, avirulent) bacteria could lead to pneumonia in mice and recovery of live SIII colonies from lungs. Since neither the boiled SIII or RII bacteria alone could cause disease, he concluded that the genetic information needed to make the SIII-type polysaccharide shell was "transforming" the RII bacteria; that is changing their genotype to allow them to make the SIII polysaccharide 1944 Avery, MaCleod and McCarty showed that DNA could cause the transformation; treatment with protease to destroy protein did not eliminate transformation, but treatment with DNAase did. Thus, they had succeeded in showing that the "transforming principle" (the agent that caused transformation) is DNA. 1952 Hershey and Chase showed that the DNA packed into the head of bacteriophage T2 is required for phage reproduction and is present in progeny, but that the protein components are not. They took advantage of radioisotopes to differentially label DNA and protein. 1956 Fraenkel-Conrat showed that the RNA present in TMV, not the protein coat, determined the type of progeny produced. The structure of DNA 1947 Chargaff showed that different species have different percentqges of the 4 nucleotides that make up DNA, but in all cases, within the limits of experimental error, the amount of A was equal to the amount of T, and that G = C. Thus the ratio of purines (A&G) to pyrimidines (T&C) in DNA is 1. X-ray diffraction studies by Wilkins and Franklin showed that DNA exists in a helix. 1953 Watson and Crick published the "double helix" model of DNA in which two strands, running in opposite directions, were held together by Hydrogen bonds between the base pairs A and T, and G and C. The base pairs are in the center of the molecule like the steps of a spiral staircase, with the phosphatesugar (deoxyribose) backbones of the two strands forming the frame. 1957 Meselson and Stahl used non-radioactive isotopes (N-14 and N-15) to show that DNA replication fits a semi-conservative model as predicted by the WatsonCrick double helix.