X. TMV STUDIES IN GENETIC CODING 509 



the parental common TMV. Others are similarly, others less pathogenic, 

 even to the point of giving no visible symptoms on two varieties of 

 tobacco. Thus, virulence may be increased or decreased by mutation. 

 However, viability, as frequently indicated by lesion size and measured 

 by lesion productivity, seems to be invariably decreased by nmtation. 

 All natural strains were less productive than common TMV, and this 

 difference is more pronounced for many chemically produced strains 

 (Veldee and Fraenkel-Conrat, 1962). Thus, as one might expect, com- 

 mon TAIV, the result of extensive selection, is probably the specimen 

 most perfectly adapted to its medium within the range of all possible 

 variations of that theme. All newly produced mutants may well have 

 appeared spontaneously at some previous time and may have fallen by 

 the wayside in the course of natural selection. 



The first mutant to be elucidated by us in structural terms, #171, 

 has illustrated one possible mechanism of biological evaluation of a 

 chemical structure of the kind that would be required for such selection 

 (Tsugita and Fraenkel-Conrat, 1960) . Resistance to enzymes is probably 

 a favorable attribute for viruses. The blocking of the N-terminus of 

 TMV protein by an acetyl group, and the enzyme blocking action of 

 proline near the C-terminus may contribute in this manner to the stabil- 

 ity of the virus. The replacement of this proline by a leucine which was 

 observed in strain #171 abolished its resistance toward the enzyme, 

 carboxypeptidase A, and it appears very possible that the lesser biolog- 

 ical viability of strain #171 can be largely attributed to this cause, 

 and thus to the particular amino acid exchange in position 156 along 

 the chain. Similarly simple explanations have not offered themselves in 

 regard to other strains. It is important to remember, however, that we 

 are able to analyze only the most viable mutants, and that we are thus 

 forced to discriminate against all the more interesting protein altera- 

 tions which render it nonfunctional. 



VII. The Coding Problem 



One of the most important problems for an understanding of the 

 mechanism of protein synthesis is the functional relationship between 

 the genetic material and the protein. Considerable evidence has accumu- 

 lated which indicates that the bulk of the genetic infomiation in typical 

 organisms is transmitted from parent to offspring through DNA. Accord- 

 ing to present information, the messages of DNA are transmitted by 

 Vv^ay of RNA (the so-called messenger RNA) and result in a specific 

 protein structure, with soluble RNA probably acting as intermediary. 

 In TMV as well as in other RNA viruses, the RNA was proven to be 

 the direct bearer of the entire genetic information required to determine 



