"On the genetic code"

Date:
1963
Reference:
PP/CRI/I/1/21
Catalogue details

Licence: In copyright

Credit: "On the genetic code". Source: Wellcome Collection.

    1/3
    Reprinted from Science, February 8, 1963, Vol. 139, No. 3554, pages 461-464 Copyright © 1963 by the American Association for the Advancement of Science On the Genetic Code Deductions about the general nature of the code are drawn from results of biochemical experimentation. It now seems certain that the amino acid sequence of any protein is deter mined by the sequence of bases in some region of a particular nucleic acid molecule. Twenty different kinds of amino acid are commonly found in pro tein, and four main kinds of base occur in nucleic acid. The genetic code de scribes the way in which a sequence of 20 or more things is determined by a sequence of four things of a different type. It is hardly necessary to stress the biological importance of the problem. It seems likely that most if not all of the genetic information in any organism is carried by nucleic acid—usually by DNA, although certain small viruses use RNA as their genetic material. It is probable that much of this information is used to determine the amino acid sequence of the proteins of that organ ism. (Whether the genetic information has any other major function we do not yet know). This idea is expressed by the classic slogan of Beadle, one gene —one enzyme, or, in the more sophis ticated but cumbersome terminology of today, one cistron—one polypeptide chain. The author is affiliated with the Medical Research Council Laboratory of Molecular Biol ogy, Cambridge, England. This article is adapted from the lecture which he delivered in Stockholm, Sweden, 11 December 1962, on receiving the Nobel prize in medicine and physiology, a prize which he shared with James D. Watson and M. H. F. Wilkins. It is published with the also be included in the complete volume of Nobel lectures in English which is published yearly by the Elsevier Publishing Company, F. H. C. Crick It is one of the more striking general izations of biochemistry—one which surprisingly is hardly ever mentioned in the biochemical text books—that the 20 amino acids and the four bases, are, with minor reservations, the same throughout nature. As far as I am aware, the presently accepted set of 20 amino acids was first drawn up by Watson and myself in the summer of 1953 in response to a letter of Gamow's. Here I shall not deal with the intimate technical details of the problem, if only for the reason that I have recently written such a review (i) which will appear shortly. Nor shall I deal with the biochemical details of messenger RNA and protein synthesis. Rather, I shall ask certain general questions about the genetic code and ask how far we can now answer them. Let us assume that the genetic code is a simple one and ask how many bases code for one amino acid. This coding can hardly be done by a pair of bases, as from four different things we can only form 4 X 4 (= 16) dif ferent pairs, whereas we need at least 20 and probably one or two more io act as spaces or for 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 amino 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 over lap. If they did, the change of a single base, due to mutation, should alter two or more (adjacent) amino acids, where as the typical change is to a single amino acid, both in the case of the spontaneous mutations, such as occur in the abnormal human hemoglobins, and in chemically induced mutations, such as those produced by the action of nitrous acid and other chemicals on tobacco mosaic virus (2). In all prob ability, therefore, codons do not over lap. This leads us to the next problem. How is the base sequence divided into codons? There is nothing in the back bone of the nucleic acid, which is per fectly regular, to show us how to group the bases into codons. If, for example, all the codons are triplets, then in addi tion to the correct reading of the mes sage there are two incorrect readings which we shall obtain if we do not start the grouping into sets of three at the right place. My colleagues and I {3) have recently obtained experimental evidence that each section of the ge netic message is indeed read from a fixed point, probably from one end. This fits in very well with the experi mental evidence, most clearly shown in the work of Dintzis (4), that the amino acids are assembled into the polypep tide chain in a linear order, starting at the amino end of the chain. Size of the Codon This leads us to the next general question: the size of the codon. How many bases are there in any one codon? The 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 3, such as 6 or 9, 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 u locus of bacteriophage T4. These mutations are believed to be due to the addition or subtraction of one or more bases from