THE PROBLEM OF NUCLEOTIDE SEQUENCE IN DEOXYRIBONUCLEIC ACIDS 85 



apparatus necessary for the production and utilization of the derivative 

 of Y that is the direct precursor of the polynucleotide chain. (2) If X and Y 

 share the same functional group (e.g. 6-keto or 6-amino) through which 

 alone the selection of the members of the newly forming chain takes place 

 — as foretold bv a mechanism postulating the replication of the comple- 

 mentarv halves of a double strand [47] — it follows that every X molecule 

 along the chain has an equal chance of being " replaced" by a Y molecule. 

 This is obviously not the case in the two systems studied by us previously 

 [37, 42] and illustrated in Fig. 2 and Table VI. One of these systems is 

 concerned with the selection of a natural analogue, a 6-aminopyrimidine, 

 the other with that of a fraudulent analogue, a 6-ketopyrimidine. In both 

 cases a discrimination, not explainable on the basis of the replication 

 scheme mentioned above, must have been operating. I shall discuss our 

 findings in the next two sections. 



SELECTION OF A NATURAL ANALOGUE 



When we deal with a natural analogue, such as the 5-methyl derivative 

 of cytosine, it is, of course, meaningless to speak of the replacement of 

 one by the other. Such a statement acquires meaning only in reference to 

 the possible mechanism of the biosynthesis of the polynucleotide chain 

 or to the existence of such principles of pleromerism as those mentioned 

 before. In other respects, in polymer chains that are not constructed 

 haphazardlv, each monomeric constituent must have its preordained 

 place; a place that it must have entered, at the time of polymerization, 

 through some form of a specific selection mechanism. A replication 

 mechanism of this nature is, indeed, offered by the scheme [47] postulating 

 a specific pairing of a 6-aminopurine (adenine) with a 6-ketopyrimidine 

 (thymine) and of a 6-ketopurine (guanine) with a 6-aminopyrimidine 

 (cytosine). 



This postulate and the fact that 5-methylcytosine is pleromeric with 

 cytosine could have led to the expectation that these two pyrimidines could 

 replace each other at random in the deoxvribonucleic acid chain, selection 

 having regard only to the presence of a 6-amino group in the pvrimidine. 

 The amazingly constant quantity of methylcytosine incorporated into the 

 deoxyribonucleic acids of wheat and rye germ (Table III, and compare also 

 the tabulation given in a previous paper [38]) should, however, render such 

 a conclusion most questionable. In what manner could a guanine residue 

 in the preformed chain exercise a preference for pairing with cvtosine, 

 rather than with methylcytosine, in the newly forming counterpart chain .- 

 There are surely limits to the amount of foresight that we can attribute 

 to an ostensiblv automatic process. 



Another observation, made repeatedly [S, 37, 38], has to do with the 



