THE PROBLEM OF NUCLEOTIDE SEQUENCE IN DEOXYRIBONUCLEIC ACIDS 7 1 



This is what we have been doing with many deoxyribonucleic acid 

 preparations. 



Remarks on nomenclature 



DEFINITION OF THE TERM " HOMOTOPE " 



If one monomeric constituent can take the position of another in a 

 definable segment of a polymer, we propose to designate it as a homotope 

 (from the Greek for occupying the same place). If in the A-chain of insulin 

 positions 8 to lo are occupied by Ala.Ser.Val in the ox [17], but by 

 Ala.Gly.Val in the sheep [18], I would say that serine and glycine are 

 homotopic with respect to this sequence. The importance of this term 

 for a consideration of nucleic acid structure will become clear presently. 



DEFINITIOxN OF THE TERM " PLEROMER " 



If in the total composition of polymers that are characterized by 

 balances such as the well-known pairing principles in deoxyribonucleic 

 acid [i, 7], and in a more limited way in ribonucleic acids [19], one con- 

 stituent can ostensibly replace another in respect to these balances, we 

 propose to designate it as a pleromer (from the Greek for filling up the 

 measure). Thus, if in the deoxyribonucleic acid of wheat germ [20] the 

 molar quantity of guanine equals that of the sum of cytosine and 5-methyl- 

 cvtosine, I would sav that these two 6-amino pvrimidines are pleromeric. 



SOLITARY AND BUNCHED NUCLEOTIDES 



A pyrimidine nucleotide that, within the polynucleotide chain of a 

 nucleic acid, is contiguous only to purine nucleotides, will be referred to as 

 "solitary"; pyrimidine nucleotides that occur in tracts of two or more, 

 flanked on both sides by purine nucleotides, will be designated as 

 "bunched" [21]. In the diagram shown in Fig. i, solitary thymidylic acid, 

 for instance, appears in positions 3, 9 and 8', bunched pyrimidine nucleo- 

 tides are seen in positions 5 to 7. 



Early attempts at sequence investigation 



Since 1947, when in an early review on deoxyribonucleic acids (p. 32 

 of ref. [22]), I first discussed the possible importance of variations in the 

 nucleotide sequence for the biological specificity of a deoxyribonucleic 

 acid, this problem has remained among the interests of my laboratory. 

 Our first chemical evidence on the existence of different deoxyribonucleic 

 acids [23, 24] made it clear that whatever "code" was carried by the 



