DEOXYPENTOSE NUCLEIC ACIDS 89 



fering from each other in the patterns of nucleotide sequence? 

 I asked this question in our first paper on the chemistry of DNA^; 

 but for several years I was resigned to there not being an answer, 

 for there is nothing more difficult at the present stage of our 

 knowledge than the fractionation of a family of closely related 

 polyampholytes of a very high molecular weight. Fortunately, I 

 had started — first together with Miss Lipshitz and later also with 

 Dr. Crampton — on a study of calf thymus nucleohistone: its 

 chemical properties and its behavior on dissociation in strong 

 salt solutions--. We found that the extent of splitting of the 

 conjugated protein into nucleic acid and protein was a function 

 of the electrolyte concentration. When the DNA portions removed 

 by fractional dissociation were analyzed, they were found to 

 exhibit a curiously graded composition^^. The stepwise extraction 

 of nucleohistone or of artificially prepared nucleates of pro- 

 teins^'''' ^^' -^ or polylysine-^ with salt solutions of increasing 

 strength under conditions favorable for the denaturation of the 

 protein moiety yielded a series of nucleic acid fractions with 

 diminishing concentrations of guanine and cytosine and rising 

 concentrations of adenine and thymine. The equimolarity of each 

 pair of constituents and of total purines and pyrimidines was, 

 however, fully maintained in all fractions^^. The weighted average 

 composition that could be computed from all fractions cor- 

 responded very closely to that found for total DNA preparations 

 of the same species. 



One may conclude that the DNA of a cell comprises an entire 

 spectrum of differently constituted individuals; a spectrum, how- 

 ever, with "bands" of different position and intensity in different 

 species. It is not inconceivable that no two nucleic acid molecules, 

 within the same nucleus, are entirely identicaP^: a prospect that 

 would seem to condemn us to forced statistics for life. 



c. Structure and sequence 



The existing evidence makes it appear likely that the nucleic 

 acids are chains in which nucleosides are linked to each other by 

 phosphoric acid diester bridges between the 5'- and 3 '-positions-'^. 



References p. 98 



