38 MALKK'E J. LiESSMAN 



XVII, the expocted pairings based on strands of opposite polarity are 

 designated by Roman numerals whereas the i)airings based on similar 

 polarity are designated i)y lower case letters. It is clear that the fit is in 

 excellent agreement with the predictions based on oj)posite polarity and 

 not with the other possibility. This represents an elegant proof of the 

 original proposal that the DNA molecule is composed of strands of 

 opposite polarity (Watson and Crick, 1953a). 



This technique was extended to other DXA types with the following 

 observations : 



1. Nearest neighbor sequence frequencies are the same in pi'oducts 

 primed with heated or unheated DNA. 



2. The nearest neighbor sequence freciuencies of DNA from A ami 

 A-dg (temperate bacteriophages) were very similar to those of the host, 

 whereas the frequencies in T2, T4, and T6 (virulent bacteriophages) 

 were markedly different from those of the host. 



3. The dinucleotide frequencies of DNA from most sources were 

 unique to the species and did not confonn to a calculated random distri- 

 bution of the bases. 



4. The dinucleotide frequencies of the DNA preparations from sev- 

 eral tissues of the same organism showed no significant variation, nor 

 did the DNA preparations from normal and neoplastic tissues of the 

 same organism (Swartz et al., 1962). 



5. The distribution of sequence frequencies in 16 DNA samples 

 analyzed conform to a mechanism for DNA replication involving pairing 

 of adenine to thymine and guanine to cytosine and are in keeping with 

 the opposite polarity of the DNA strands. 



6. The nearest neighbor sequence frequencies of a jM'oduct primed 

 with native calf thymus DNA or primed with newly synthesized "calf 

 thymus" DNA (containing less than 5% of the original native DNA) 

 were the same. From this it may be inferred (though not proved) that 

 the sequence frequencies in the product are indicative of the sequence 

 frequencies in the native DNA. 



An interesting application of the nearest neighbor analysis is the 

 recent investigation (Swartz et nl., 1962) of whether both strands 

 of the double-strand fonn of DNA from the small bacteriophage 0X174 

 (Sinsheimer, 1959) can serve as templates in DNA rejilication. When the 

 single-stranded form of 0X174 is used to prime a reaction in wliicli (^acli 

 strand of the original DNA replicates once, the composition of the newly 

 formed strand should be complementaiy to the original. An ex|)erinient 

 was devised in which DN'A synthesis was allowed to proceed until 20% 

 of the original DN'A was replicated, thus minimizing the chance of 

 multiple rounds of replication. The product of this reaction was analyzed 



