30 THE BIOSYNTHESIS OF PROTEINS 



Comparison of the analytical data obtained on a great many specimens 

 of DNA brought to light a striking regularity or common principle of DNA 

 composition: whatever the origin of the DNA samples, the number of 

 adenine molecules was found to be equal to the number of thymine 

 residues, and guanine and cytosine on the other hand were always present 

 in equimolecular amounts (Chargaff, 1950). The fundamental significance 

 of this rule was fully realized only \vhen a satisfactory model of macro- 

 molecular structure was worked out for DNA. 



Gulland et al. (1947) had observed that DNA solutions undergo irrevers- 

 ible changes in viscosity and in ionization characteristics outside a certain 

 pH range. This made it probable that DNA as isolated contains labile 

 bonds, e.g. hydrogen bonds, between ionizable groups. Since titration 

 hysteresis persists at very low DNA concentrations, the labile bonds are 

 probably located within each molecule, not between molecules (Jordan 

 et al., 1956). A considerable irreversible increase in ultraviolet absorption 

 is brought about by lowering the pH for a short time or by heating DNA 

 especially in solutions of low ionic strength (Thomas, 1951, 1953, 1954), 

 indicating irreversible changes in electronic state of the heterocycles. 



It is clear that DNA, like proteins, can be denatured by rather mild 

 treatments and that its macromolecular structure is held together by labile 

 bonds in which ionizable groups of the ultraviolet absorbing heterocycles 

 are involved. DNA denaturation has been extensively studied, it manifests 

 itself by changes in viscosity (Doty and Rice, 1955), streaming birefringence 

 (Mathieson and Matty, 1955), rotatory dispersion (James and Levendahl, 

 1955), infrared absorption (Frick and Rosenberg, 1954; Blow and Lenor- 

 mant, 1955), UV absorption (Thomas, 1951, 1953, 1954), affinity for 

 certain dyes (Thomas, 1953), and sedimentation characteristics (Alexander 

 and Stacey, 1955, Oth, 1959). 



X-ray diffraction studies indicated a helical structure of DNA molecules 

 (Wilkins et al., 1953 ; Franklin and Gosling, 1953). The size of the structural 

 unit and the density of DNA suggested that there must be two chains in the 

 unit (Crick, 1954). Model building showed that the chains are probably 

 held together by bonds between pairs of bases, and the best fit is obtained 

 by pairing adenine with thymine and guanine with cytosine (Pauling and 

 Corey, 1956). This was in agreement with the experimental fact that 

 adenine and thymine on one hand and guanine and cytosine on the other 

 are always found in equimolecular proportions in DNA. 



Watson and Crick (1953) thus proposed the now famous double helix 

 structure for DNA in which the two chains run in opposite directions; each 

 adenine in one chain is linked by hydrogen bonding to a thymine in the 

 other, and each guanine to a cytosine (or a cytosine derivative). The para- 

 meters of this structure or of a slightly modified version of it (Feughelman 

 et al., 1955; Langridge et al., 1960) are in good agreement with X-ray 



