THE PROBLEM OF NUCLEOTIDE SEQUENCE IN DEOXYRIBONUCLEIC ACIDS 87 



sequences, such as purine-thymine-purine and purine-bromouracil- 

 purine, but the intrusion of the halopyrimidine seems to have brought 

 about so drastic a reorganization of the nucleotide pattern as to imply the 

 existence of two distinct populations of polymers. We may be able to fool 

 the cell, but it is no longer the same cell. 



In the cells that were cultivated in the presence of the halopyrimidine, 

 the nucleic acid contains nearly twice as many solitary pyrimidine residues 

 as does the normal preparation; the frequency of the sequences purine- 

 cytosine-purine has doubled; and, relative to the total concentration of 

 thymine, even the runs of purine-thymine-purine have increased. In 

 addition — and this is quite remarkable — almost one-third of the in- 

 corporated bromouracil is found flanked by purines in the form of solitary 

 units. The abundance of the coupled unit purine-cytosine-purine has, 

 however, been relatively little changed. 



At the same time, as Table V shows, 5-bromouracil and thymine 

 definitely are treated as pleromers. 



THE CONCEPTS OF PLEROMERISM AND HOMOTOPY AND THE NEIGHBOUR 



PROBLEM 



The definitions of the suggested terms "pleromer" and "homotope" 

 have been given above. The compilation in Table VII, by no means 

 complete, gives a few examples of such pleromeric relationships in de- 

 oxyribonucleic acids. There can be little doubt that in all these instances 

 the established pairing relationships would have been destroyed, had the 

 minor pleromer been omitted from the computations. Only one satellite 

 normally occurring in nature, viz. 5-methylcytosine, could be included in 

 the Table. Another minor component — if it can be classified as a normal 

 constituent — namely, N-methyladenine, plays a baffling role. It has been 

 reported to occur, among other instances, in the deoxyribonucleic acid of 

 a thymine auxotroph of E. coli in not inconsiderable quantity [49]. Under 

 special conditions of growth, its concentration increases, somewhat in 

 measure with a decrease in the amount of thymine. It is, however, at the 

 moment difficult to see through what mechanism a 6-ketopyrimidine and 

 a 6-methylaminopurine could function as pleromers. 



Pleromic relationships in ribonucleic acids are much more difficult to 

 establish, as the only complementariness useful for scrutiny is the equality 

 of the 6-amino and 6-ketonucleotides [19]. Of the three examples listed 

 in Table VIII only the one dealing with the incorporation of 5-ffuorouracil 

 (52) carries conviction. It is not impossible that, when more careful 

 analyses become available, 8-azaguanine and guanine will also emerge as 

 pleromers. 



The usefulness of the concept of homotopy is, for the time being, more 



