ON THE GENETIC CODE 



T4. These mutations are believed to be due to the addition or subtraction of 

 one or more bases from the genetic message. They are typically produced 

 by acridincs, and cannot be reversed by mutagens which merely change one 

 base into another. Moreover these mutations almost always render the gene 

 completely inactive, rather than partly so. 



By testing such mutants in pairs we can assign them all without exception 

 to one of two classes which we call -j- and — . For simplicity one can think 

 of the + c l ass as having one extra base at some point or other in the genetic 

 message and the — class as having one too few. The crucial experiment is to 

 put together, by genetic recombination, three mutants of the same type into 

 one gene. That is, either ( -\- with -f- with -+- ) or ( — with — with — ) . Where- 

 as a single -f or a pair of them ( + with -(- ) makes the gene completely 

 inactive, a set of three, suitably chosen, has some activity. Detailed examina- 

 tion of these results show that they are exactly what we should expect if the 

 message were read in triplets starting from one end. 



We are sometimes asked what the result would be if we put four -|-'s in 

 one gene. To answer this my colleagues have recently put together not 

 merely four but six -f-'s. Such a combination is active as expected on our 

 theory, although sets of four or five of them are not. We have also gone a 

 long way to explaining the production of « minutes » as they are called. That 

 is, combinations in which the gene is working at very low efficiency. Our 

 detailed results fit the hypothesis that in some cases when the mechanism 

 comes to a triplet which does not stand for an amino acid (called a « non- 

 sense » triplet) it very occasionally makes a slip and reads, say, only two bases 

 instead of the usual three. These results also enable us to tie down the direc- 

 tion of reading of the genetic message, which in this case is from left to right, 

 as the Tn region is conventionally drawn. We plan to write up a detailed 

 technical account of all this work shortly. A final proof of our ideas can only 

 be obtained by detailed studies on the alterations produced in the amino acid 

 sequence of a protein by mutations of the type discussed here. 



One further conclusion of a general nature is suggested by our results. It 

 would appear that the number of nonsense triplets is rather low, since we 

 only occasionally come across them. However this conclusion is less secure 

 than our other deductions about the general nature of the genetic code. 



It has not yet been shown directly that the genetic message is co-linear 

 with its product. That is, that one end of the gene codes for the amino end 

 of the polypeptide chain and the other for the carboxyl end, and that as one 

 proceeds along the gene one comes in turn to the codons in between in the 



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