[962 P.H. C. CRICK 



problem, if only for the reason that 1 have recently written such a review 1 

 which will appear shortly. Nor shall I deal with the biochemical details of 

 messenger KNA and protein synthesis, as Watson has already spoken about 

 these. Rather I shall ask certain general questions about the genetic code and 

 ask how tar we can now answer them. 



1 et us assume that the genetic code is a simple one and ask how many- 

 bases code tor one amino acid? This can hardly be done by a pair of bases, 

 .is from tour different things we can only form 4x4=16 different pairs, 

 whereas we need at least twenty and probably one or two more to act as 

 spaces or tor other purposes. However, triplets of bases would give us 64 

 possibilities. It is convenient to have a word for a set of bases which codes 

 one ammo acid and I shall use the word «codon» for this. 



This brings us to our first question. Do codons overlap? In other words, 

 as we read along the genetic message do we find a base which is a member of 

 two or more codons? It now seems fairly certain that codons do not overlap. 

 It they did, the change of a single base, due to mutation, should alter two or 

 more (adjacent) amino acids, whereas the typical change is to a single amino 

 acid, both in the case of the « spontaneous » mutations, such as occur in the 

 abnormal human haemoglobin or in chemically induced mutations, such as 

 those produced by the action of nitrous acid and other chemicals on tobacco 

 mosaic virus 2 . In all probability, therefore, codons do not overlap. 



This leads us to the next problem. How is the base sequence, divided into 

 codons? There is nothing in the backbone of the nucleic acid, which is 

 perfectly regular, to show us how to group the bases into codons. If, for 

 example, all the codons are triplets, then in addition to the correct reading 

 of the message, there are two ///correct readings which we shall obtain if 

 we do not start the grouping into sets of three at the right place. My col- 

 leagues and [ 3 have recently obtained experimental evidence that each section 

 of the genetic message is indeed read from a fixed point, probably from one 

 end. This fits in very well with the experimental evidence, most clearly 

 shown 111 the work of Dintzis 4 that the amino acids arc assembled into the 

 polypeptide chain in a linear order, starting at the amino end of the chain. 



This leads us to the next general question: the size of the codon. How 

 many bases are there in any one codon? The same experiments to which I 

 have just referred 3 strongly suggest that all (or almost all) codons consist of 

 a triplet of bases, though a small multiple of three, such as six or nine, is not 

 completely ruled out by our data. We were led to this conclusion by the 

 study of mutations in the A and B cistrons of the r„ locus of bacteriophage 



s-136 



