ON THE GENETIC CODE 



uracil and cytosinc in (presumably) random order will increase the incor- 

 poration of the amino acids phenylalanine, serine, leucine, and proline, and 

 possibly threonine. By using polymers of different composition and assum- 

 ing a triplet code one can deduce limited information about the composition 

 of certain triplets. 



From such work it appears that, with minor reservations, each polynu- 

 cleotide incorporates a characteristic set of amino acids. Moreover the four 

 bases appear quite distinct in their effects. A comparison between the triplets 

 tentatively deduced by these methods with the changes in amino acid se- 

 quence produced by mutation shows a fair measure of agreement. Moreover 

 the incorporation requires the same components needed for protein syn- 

 thesis, and is inhibited by the same inhibitors. Thus the system is most 

 unlikely to be a complete artefact and is very probably closely related to 

 genuine protein synthesis. 



As to the actual triplets so far proposed it was first thought that possibly 

 every triplet had to include uracil, but this was neither plausible on theoret- 

 ical grounds nor supported by the actual experimental evidence. The first 

 direct evidence that this was not so was obtained by my colleagues Bretscher 

 and Grunberg-Manago 8 , who showed that a poly (C,A) would stimulate 

 the incorporation of several amino acids. Recently other workers 9 - 10 have 

 reported further evidence of this sort for other polynucleotides not con- 

 taining uracil. It now seems very likely that many of the 64 triplets, possibly 

 most of them, may code one amino acid or another, and that in general sev- 

 eral distinct triplets may code one amino acid. In particular a very elegant 

 experiment 11 suggests that both (UUC) and (UUG) code leucine (the 

 brackets imply that the order within the triplets is not yet known). This 

 general idea is supported by several indirect lines of evidence which cannot 

 be detailed here. Unfortunately it makes the unambiguous determination of 

 triplets by these methods much more difficult than would be the case if there 

 were only one triplet for each amino acid. Moreover, it is not possible by 

 using polynucleotides of « random » sequence to determine the order of bases 

 in a triplet. A start has been made to construct polynucleotides whose exact 

 sequence is known at one end, but the results obtained so far are suggestive 

 rather than conclusive 12 . It seems likely however from this and other unpub- 

 lished evidence that the amino end of the polypeptide chain corresponds to 

 the « right-hand » end of the polynucleotide chain - that is, the one with the 

 2', 3' hydroxyls on the sugar. 



It seems virtually certain that a single chain of RN A can act as messenger 



s-139 



