Genetic Co?itrol of Protein Synthesis 63 



of substitutions of one amino acid for another have been found in 

 the abnormal hemoglobins (7) which are presumed to be products 

 of a mutationally altered globin gene. In addition, mutant bac- 

 terial strains producing an altered alkaline phosphatase (8) and 

 an altered tryptophan synthetase (9) have been shown to have 

 substituted one amino acid for another. Similarly, a number of 

 substitutions have been described in tlie tobacco mosaic virus "coat 

 protein" (10). 



From the sequence hypothesis, it is a short step to the usual 

 statement of the "genetic coding problem": how the sequence of 

 four bases in DNA specifies the twenty amino acids commonly 

 occurring in protein. The first step toward "solving" the coding 

 problem is really to show that the problem as stated exists— to 

 demonstrate that the base sequence of DNA does specify the amino 

 acid sequence of the protein. On the protein side, evidence that 

 mutations can cause amino acid substitutions has been men- 

 tioned. On the DNA side, the determination of nucleotide sequence 

 is not possible at present, but a prediction (or corollary) to the 

 sequence hypothesis has been used to arrive at an experimentally 

 feasible system. This prediction states that the order and relative 

 position of point mutations within the structural gene for a par- 

 ticular protein, presumably reflecting base alterations, should 

 correspond to the order and relative position of amino acid sub- 

 stitutions in proteins produced by these mutated genes. 



Work on the bacterial enzymes alkaline phosphatase (8) and 

 tryptophan synthetase (9) has shown that two mutations linked 

 genetically affect amino acids in the same region of the respective 

 proteins, so that we can feel some confidence that the sequence 

 hypothesis is correct. Can one determine which bases code which 

 amino acids by this combined genetic and protein chemical 

 approach? The answer is probably yes, provided that mutagens 

 specific for a single base can be developed and used; but the 

 number of amino acid substitutions which must be accumulated 

 is almost prohibitively large. Recently, a much more direct 

 approach to working out the nature of the genetic code and 

 probably its explicit solution has appeared somewhat unexpectedly 

 on the scene. This approach indicates that the future of the work 

 with mutationally altered proteins probably lies in the realm of 



