POSTSCRIPT 401 



III. CORRELATION BETWEEN AMINO ACID SUBSTITUTIONS AND 

 GENE MUTATIONS. 



Work with several bacterial proteins as well as with hemoglobin and 

 TMV-protein has all supported the hypothesis that single nucleotide 

 changes in the gene can result in single amino acid substitutions in the 

 corresponding protein. Although single nucleotide changes are not the 

 onlv molecular basis of mutation, they clearly represent one important 

 class. 



In the tryptophane synthetase system of E. coli (p. 276), amino acid 

 substitutions have been identified in some mutants. For example, in 

 mutant A-23, glycine present in the wild-type has been changed to 

 arginine in one position in the protein. In the mutant A-46, which maps 

 at the same site, the same glycine has been changed to glutamic acid. 

 According to the present code, glycine is coded by UGG, glutamic acid 

 by UAG, and arginine by UCG. Thus the change from glycine to glutamic 

 acid involves the single nucleotide change from G to A, and in the case 

 of arginine from G to C. 



No biochemical method exists as yet for determining the coding se- 

 quence within the triplet, but Yanofsky has presented a genetic method 

 for achieving this result. Although mutants A-23 and A-46 map at or near 

 the same site, it is possible to recover rare wild-type recombinants. If 

 the mechanism of recombination is actually at the nucleotide level, then 

 the recovery of the wild-type makes possible an ordering of the triplets. 

 Glutamic acid would have to be coded UAG and arginine UGC, in order 

 to recover glvcine which is UGG. The other recombinant, predicted but 

 not found, would have to be UAG and would provide further confirma- 

 tion. Of course the direction in which these triplets are read is not 

 yet known. 



It is appropriate to conclude this summary of recent advances in 

 molecular genetics with an experiment that epitomizes the nature of this 

 field, combining the most elaborate biochemical methods of fingerprinting 

 and amino acid sequence analysis with the sophisticated simplicity of 

 the genetic cross. 



BIBLIOGRAPHY 



Cold Spring Harbor Symp. Quant. Biol. 26:1-408 (1961) Cellular Regulatory 



Mechanisms. 

 Bautz, E. K. F, and B. D. Hall, 1962. The Isolation of T4-specific RNA on a 



DNA-Cellulose column. Proc. Natl. Acad. Sci. Wash. 48:400-408. 



