CONCEPTUAL BASIS 127 



"The results serve to disprove the tetranucleotide hypothesis. It is, 

 however, noteworthy — whether this is more than accidental, cannot yet 

 be said — that in all deoxypentose nucleic acids examined thus far the 

 molar ratios of total purines to total pyrimidines, and also of adenine to 

 thymine and of guanine to cytosine, were not far from 1." 



You will recognize here, among other things, the first statement 

 of the well-known pairing principles. 



Even the earliest observations on the nucleic acids, which 

 showed the existence of remarkable similarities and, at the same 

 time, of outstanding differences in the distribution and, there- 

 fore, the sequence of the constituent monomers, the nucleotides, 

 made it appear of great interest to learn something about the 

 structural principles that came into play. I shall first discuss some 

 of the basic concepts that must be considered. 



2. REMARKS ON THE CONCEPTUAL BASIS OF SEQUENCE ANALYSIS 



a. The problem of homogeneity 



What determines the composition of a given biological polymer 

 has been much discussed in the recent past, at any rate in regard 

 to proteins and nucleic acids. Almost no attention has been paid, 

 as has been pointed out recently^, to the presumably equally rigid 

 control of the composition of other cell-specific polymers, such 

 as the polysaccharides or even certain macromolecular lipids. 

 The usual expedient, in which I wish I could concur with greater 

 enthusiasm^, has been the formulation of some sort of template 

 which obviously makes up in versatility for what it lacks in con- 

 creteness. This Disneyland of templates and pools and feedbacks, 

 presided over by never-smiling augurs, will make us the laughing 

 stock of later times. 



What determines the size of a given biological polymer has, on 

 the other hand, been neither determined nor even much discussed. 

 The cell will in many instances contain, or at least it will be 

 made to yield, compounds belonging to the same class, but very 

 much different in size. Proteins, the best investigated group of 

 cellular macromolecules, vary in size over a considerable range. 



References p. 159 



