"On the genetic code" (Nobel Lecture)

Date:
1963
Reference:
PP/CRI/I/1/20
Catalogue details

Licence: In copyright

Credit: "On the genetic code" (Nobel Lecture). Source: Wellcome Collection.

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    in another class of codes, that its complement will stand for no amino It has recently been shown by Ochoa's group that poly A stimulates the incorporation of lysine (10). Thus presumably AAA codes lysine. However since UUU codes phenylalanine these facts rule out all the above codes. It is also found that poly (U, G) incorporates quite different amino acids from poly (A, C). Similarly poly (U, C) differs from poly (A, G) (9 and 10). Thus there is little chance that any of this class of theories will prove correct. Moreover they are all, in my opinion, unlikely for general theoretical reasons. A start has already been made, using the same polynucleotides in cell- free systems from different species, to see if the code is the same in all organisms. Eventually it should be relatively easy to discover in this way if the code is universal, and, if not, how it differs from organism to organism. The preliminary results presented so far disclose no clear difference be tween E. coli and mammals, which is encouraging (10 and 13). At the present time, therefore, the genetic code appears to have the fol lowing general properties : (1) Most if not all codons consist of three (adjacent) bases. (2) Adjacent codons do not overlap. (3) The message is read in the correct groups of three by starting at some fixed point. (4) The code sequence in the gene is co-linear with the amino acid se quence, the polypeptide chain being synthesized sequentially from the amino end. (5) In general more than one triplet codes each amino acid. (6) It is not certain that some triplets may not code more than one amino acid, i. e. they may be ambiguous. (7) Triplets which code for the same amino acid are probably rather similar. (8) It is not known whether there is any general rule which groups such codons together, or whether the grouping is mainly the result of historical accident. (9) The number of triplets which do not code an amino acid is probably small. (10) Certain codes proposed earlier, such as comma-less codes, two or three-letter codes, the combination code, and various transposible codes are all unlikely to be correct. (11) The code in different organisms is probably similar. It may be the same in all organisms but this is not yet known. Finally one should add that in spite of the great complexity of protein synthesis and in spite of the considerable technical difficulties in synthe sizing polynucleotides with defined sequences it is not unreasonable to hope that all these points will be clarified in the near future, and that the genetic code will be completely established on a sound experimental basis within a few years. The references have been kept to a minimum. A more complete set will be found in the first reference. (1). F. H. C. Crick in Progress in Nucleic Acid Research, ed. J. N. Davidson and Waldo E. Cohn, Academic Press Inc., New York, in press. (2). H. G. Wittmann, Z. Vererbungslehre 93, 491, (1962). A. Tsugita, J. Mol. Biol., 5, 284 and 293 (1962). (3). F. H. C. Crick, L. Barnett, S. Brenner, and R.J. Watts-Tobin, Nature, 192, 1227, (1961). (4). M. A. Naughton and Howard M. Dintzis, Proc. Nat. Acad. Sci., U. S., 48, 1822 (1962). (5). G. von Ehrenstein and F. Lipmann, Proc. Nat. Acad. Sci., U. S., 47, 941, (1961). (6). J. H. Matthaei and M. W. Nirenberg, Proc. Nat. Acad. Sci., U. S., 47, 1580, (1961); M. W. Nirenberg and J. H. Matthaei, Proc. Nat. Acad. Sci., U. S., 47, 1588, (1961); M. W. Nirenberg, J. H. Matthaei and O. W. Jones, Proc. Nat. Acad. Sci., U. S., 48, 104 (1962); J. H. Matthaei, O. W. Jones, R. G. Martin and M. W. Nirenberg, Proc. Nat. Acad. Sci., U. S., 48, 666 (1962). (7). P. Lengyel, J. F. Speyer and S. Ochoa, Proc. Nat. Acad. Sci. U. S., 47, 1936 (1961) ; J. F. Speyer, P. Lengyel, C. Basilio and S. Ochoa, Proc. Nat. Acad. Sci., U. S., 48, 63 (1962); P. Lengyel, J. F. Speyer, C. Basilio and S. Ochoa, Proc. Nat. Acad. Sci., U. S., 48, 282 (1962); J. F. Speyer, P. Lengyel, C. Basilio and S. Ochoa, Proc. Nat. Acad. Sci., U. S., 48, 441 (1961); C. Basilio, A. J. Wahba, P. Lengyel, J. F. Speyer and S. Ochoa, Proc. Nat. Acad. Sci., U. S., 48, 613 (1962). (8). M. S. Bretscher and M. Grunberg-Manago, Nature, 195, 283 (1962). (9). O. W.Jones and M. W. Nirenberg, Proc. Nat. Acad. Sci., U. S. 48, 2115, (1962). (10). R. S. Gardner, A.J. Wahba, C. Basilio, R. S. Miller, P. Lengyel and J. F. Speyer, Proc. Nat. Acad. Sci., U. S. 48, 2087, (1962). (11). B. Weisblum, S. Benzer and R.W.Holley, Proc. Nat. Acad. Sci., U.S. 45,1449, (1962). (12). A. J. Wahba, C. Basilio, J. F. Speyer, P. Lengyel, R. S. Miller and S. Ochoa, Proc. Nat. Acad. Sci., U. S., 48, 1683 (1962). (13). H. R. V. Arnstein, R. A. Cox and J. A. Hunt, Nature, 194, 1042 (1962); E. S. Maxwell, Proc. Nat. Acad. Sci., U. S., 48, 1639 (1962); I. B. Weinstein and A. N. Schechter, Proc. Nat. Acad. Sci., U. S., 48, 1686 (1962).