The Problem of Nucleotide Sequence in 

 Deoxyribonucleic Acids 



Erwin Chargaff 

 Columbia University, New York, N. Y., U.S.A. 



Introduction 



Now that some of the most tremendous problems in biochemistry have, 

 it is said, been solved successfully — such as the nature of the genetic 

 material, its structure and mode of replication, and even its biosynthesis — 

 our time, tired of so much exertion, may take a deep breath and then, 

 perhaps, decide that it all has to be done over again. I should not dare 

 contradict, for I have always been more impressed by the enormity of the 

 gap between claim and achievement than by the magnitude of the former. 



In any event, we have set ourselves a much, more modest, but by no 

 means easv, task, namely, the elucidation of some of the aspects of the 

 primary structure of deoxyribonucleic acids, especially in regard to the 

 arrangement of the nucleotide constituents. In this connection, and since 

 this talk is given in Stockholm, I may be permitted to recall that it was 

 here, and also in Uppsala, that I had the first opportunity to review our 

 original observations on deoxyribonucleic acid. This is what I said in 

 1949 and what was printed a few months later [i]. 



"The desoxypentose nucleic acids extracted from different species 

 thus appear to be different substances or mixtures of closely related 

 substances of a composition constant for different organs of the same 

 species and characteristic of the species. 



"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 desoxypentose 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 i." 



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, therefore, the sequence of the con- 

 stituent monomers, the nucleotides, made it appear of great interest to 



