152 NUCLEOTIDE SEQUENCE IN DEOXYRIBONUCLEIC ACIDS 



view of current replication hypotheses at a previous occasion^'^. 

 An even more impressive difference between the ways in which 

 methylcytosine and cytosine are selected for insertion into the 

 polynucleotide emerges from the study of the frequency of these 

 pyrimidines as solitary and bunched nucleotides^"^. As will be 

 seen in Fig. 12, a remarkably large proportion of methylcytosine, 

 and a surprisingly small proportion of cytosine, exist as solitary 

 units. These two 6-aminopyrimidines can hardly share a common 

 pattern of nucleotide sequence. What is, however, remarkable is 

 that the mole fractions of 5-methylcytosine and thymine ap- 

 pearing as solitary units are nearly equal in most instances. One 

 must conclude that, whereas there is evidence that the two 6- 

 aminopyrimidines are not treated indiscriminately by the selection 

 mechanism, there is some indication that no such distinction is 

 exercised in regard to the two 5-methylpyrimidines. In the terms 

 defined above, cytosine and 5-methylcytosine are pleromers, but 

 not homotopes; thymine and 5-methylcytosine appear to be 

 homotopic with respect to the sequence purine-pyrimidine- 

 purine, although they are not pleromeric. 



e. Selection of a fraudulent analogue 



It is striking that almost all extraneous purine or pyrimidine 

 analogues that can, by the living cell, be incorporated massively 

 into nucleic acids — e.g., 5-bromo-, 5-chloro- or 5-iodouracil into 

 deoxyribonucleic acid, 5-fluorouracil or 8-azaguanine into 

 ribonucleic acid — belong to the 6-keto type. In the instance in- 

 vestigated in the greatest detail, viz., the incorporation of 5- 

 bromouracil into the deoxyribonucleic acid of E. coli, the problem 

 of replacement can be posed directly. In the case of a natural 

 satelUte, such as 5-methylcytosine, the complement appears to be 

 fixed rigidly by the cell, whereas no obvious cellular mechanism, 

 except the death of the cell, can be discerned that would limit the 

 extent of incorporation of the halopyrimidine. One would expect 

 the cell to discriminate between a foreign intruder and the normally 

 required thymine; but the auxotroph apparently can be inveigled 

 into accepting the substitute, very much in contrast to the wild type. 



