The Infective Nucleic Acid from 

 Tobacco Mosaic Virus 



H. FRAENKEL-CONRAT & B. SINGER 



Virus Laboratory, University of California, Berkeley, California, U.S.A. 



Of the two constituents of tobacco mosaic virus (TMV), the nucleic acid has, 

 in recent years, come to occupy that central role in our interest which was 

 formerly played by the protein. This is due to the realization that the nucleic 

 acid alone can perform all the crucial functions of the virus, namely it can 

 initiate infection and transmit the required genetic information [1-5]. This 

 conclusion was not easily arrived at, because of the comparatively low efficiency 

 of the nucleic acid as an infectious agent, and its great sensitivity to various 

 materials, including one so seemingly harmless as o-i m phosphate buffer (pH 7). 

 These difficulties in detecting and estimating the infectivity of the nucleic acid 

 can be overcome by reconstituting new virus from it and added protein. The 

 number of lesions given by a certain amount of nucleic acid is in that manner 

 increased 10- to many 100-fold, and the sensitivity of the nucleic acid to salts, 

 ribonuclease, metals etc. is abolished. It was in this manner that the infectivity 

 of the nucleic acid was first detected [6], 



The useful protecting activity of the protein represents an expression of its 

 primary biological function. It continues to be of great interest to us what kind 

 of bonds and affinities are involved in the remarkable ability of this particular 

 protein to build up the macromolecular housing for the viral nucleic acid. But 

 apart from its architectural role, the protein is also of considerable interest, 

 because it represents an expression in terms of amino-acid sequences of informa- 

 tion carried and transmitted by nucleotide sequences. Thus this system may 

 represent the Rosetta stone of biochemical genetics, and the unravelling of this 

 amino acid sequence may give us the clue needed for the deciphering of the 

 meaning of nucleic acid structure. For all these reasons, our laboratory is actively 

 engaged in the analysis of the structure of the TMV protein. 



However, to the Symposium devoted to the origin of life, the nature of the 

 nucleic acid may be of greater concern. For whatever claims to life viruses may 

 possess, these are properties of the nucleic acid. And while viruses probably 

 represent highly adapted twentieth century agents, evolved, be it forward or 

 backward, to assure optimal survival value, their nucleic acid may be consider- 

 ably closer in nature and structure to some primordial polynucleotide molecules. 

 Thus, if we wish to assume that the most fundamental processes of life have 

 always reUed on the same principle mechanisms, then what we learn about the 

 relationship of structure and function in viral or other genetically active nucleic 



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