454 rollin d. hotchkiss 



3. Implications of a Genetic Role — Biochemical Specificity of DNA 



Some 30 different transforming factors have been mentioned as occurring 

 in DNA preparations of apparently similar properties from different 

 bacterial strains. Indeed, it appears that as soon as new specific trans- 

 forming agents are defined they are recognized in the DNA fraction of the 

 appropriate cells. It must then be supposed that these preparations, highly 

 purified according to the usual criteria, have latitude for specific differ- 

 ences of composition or configuration within the DNA structure itself, 

 allowing for the many genetic factors observed and for the multitude of 

 others to be expected. 



Certainly some specific biological patterns are not inherited in the form 

 of DNA or DNA-proteins. A number of plant viruses, at least, are PNA- 

 proteins. The same may be true of cytoplasmic structural entities such as 

 the mitochondria and microsomes, which have certain heritable aspects. 

 Proteins, of course, can manifest and maintain specific patterns, and may 

 well transmit them. Nevertheless, it is a striking fact that most living 

 replicated units which have been investigated, including perhaps the 

 majority of the viruses, are known to contain DNA, and those which do 

 not, appear to contain its relative, PNA. 



It may be well to recall here that such polysaccharides as glycogen, 

 although sometimes described as "self-duplicating" or as templates capable 

 of determining their own biosynthesis, are not such in reality. As Cori and 

 Cori^i^ have clearly indicated, "primers" of carbohydrate biosynthesis 

 furnish appropriate end glycosidic residues upon which polysaccharide 

 synthesis takes place in a pattern determined entirely by the enzymes 

 present and not necessarily related to that of the "primer." 



a. Specificity in Chemical Composition or Configuration 



It has been described in Chapter 10 that DNA's of different species 

 may show differences in purine and pyrimidine base content. There is, 

 furthermore, considerable uniformity in the composition of the DNA 

 isolated from different tissues of the same species. Once variations in base 

 content were established, it became clear that DNA's might have a wide 

 variety of different structures, as predicted from a consideration of the 

 biological activities of the bacterial DNA's. 



Indeed, new pyrimidine bases qualitatively distinct from the usual 

 cytosine and thymine, have been found in a few sources. One of these, 

 5-methylcytosine, is apparently absent from many bacterial and virus 

 DNA's''^-''^ but constitutes an appreciable percentage of the total bases of 



"2 G. T. Cori and C. F. Cori, /. Biol. Chem. 151, 57 (1943). 



"3 E. Vischer, S. Zamenhof, and E. Chargaff, J. Biol. Chem. 177, 429 (1949). 



114 J. D. Smith and G. R. Wyatt, Biochem. J. 49, 144 (1951). 



"6 G. R. Wyatt, J. Gen. Physiol. 36, 201 (1952). 



