I.    Historical perspective
    A.  Thought genetic material must be protein
        1.  More complex (20 amino acids vs. 4 bases)
        2.  Both protein and DNA in nucleus
    B.  P. Levene, W. Jacobs and others
        1.  RNA - ribose + four bases
        2.  DNA - deoxyribose + four bases
        3.  Bases appeared in approximately equal proportions
        4.  Tetranucleotide hypothesis: DNA was boring repetitive molecule
    C.  Transforming principle - Griffiths 1928
        1.  Three types of capsules I, II, III
             a.  If mutation, don't form capsule
             b.  Visible as rough colonies
        2.  R type + heat-killed S converts R to S
    D.  Identity of transforming principle - Avery, MacLeod & McCarty 1944
        1.  Digest molecules with enzymes
        2.  Only when DNA destroyed is transformation prevented
        3.  Additional support
            a.  Ultracentrifugation: high molecular weight
            b.  Electrophoresis: highly mobile (characteristic of DNA)
            c.  UV absorption spectrophotometry: absorption of DNA
            d.  Elementary chemical analysis: N/P ratio of 1.67 (DNA, not higher value expected of protein)
    E.  Chargaff 1950
        1.  A+G = T+C
        2.  A=T
        3.  G=C
        4.  But G-C content varied among species
        5.  Disproved tetranucleotide hypothesis
    F.  Blender experiment - Hershey & Chase 1952 [date in book incorrect]
        1.  Label proteins or nucleic acids
        2.  Only labeled nucleic acid enters cell
   G.  Fraenkel-Conrat and Williams
       1.  RNA virus (TMV)
       2.  Reassociated; phenotype depended on source of RNA
       3.  RNA can also be genetic material
II.  Structure of nucleic acids
    A.  Pentose
        1.  Deoxyribose (DNA)
        2.  Ribose (RNA)
    B.  Nitrogenous bases
       1.  Purines
           a.  Adenine
           b.  Guanine
       2.  Pyrimidines
           a.  Cytosine
           b.  Thymine (DNA)
           c.  Uracil (RNA)
    C.  Sugar-phosphate backbone
        1.  Phosphodiester bonds
        2.  Antiparallel
        3.  5' phosphate
        4.  3' OH
    D.  A = T, G = C, A + G = T + C 'Chargaff's rule' 1952
    E.  Franklin and Wilkins 1953
        1.  DNA is double helix
        2.  Right handed
        3.  Major and minor grooves
        4.  Sugar-phosphate backbone on outside
      F.  Watson and Crick 1953
        1.  Antiparallel
        2.  Hydrogen bonding, A pairs with T, G pairs with C
            a.  A-T 2 H-bonds
            b.  G-C 3 H-bonds
            c.  Unequal spacing of two strands
                (1).  major groove
                (2).  minor groove
    G.  A-, B- and Z-DNA
        1.  See table, p. 212
        2.  B DNA is found in cell
        3.  Z DNA may be involved in regulation