Order in the genetic code.

While it is important to know what the genetic code codon assignments are, it is more important to know why they are, i.e., to know the mechanisms giving rise to the particular assignments observed. Only when the latter question is answered can we truly claim to begin to understand the genetic code. To date, however, most scientific attention has been turned to the former question. The reasons for this are quite clear. For one, the experimental systems for answering what the codon assignments are have been developed and are rapidly yielding a solution, while those for elucidating why such codon assignments exist are either not yet discovered or are very far from yielding the sought-for answer. For another reason, the adaptor hypothesis, one of the central dogmas of the coding field today, predicts the answer to the "why" question to be entirely uninteresting and trivial. The prediction here is that the codons are assigned to amino acids merely by "historical accidents," and thus no causal relationship between an amino acid and its codon exists. ' Another way of putting this is: were the genetic code to evolve again (under the same conditions), the codon assignments would be unrelated to those now observed. I shall not debate the validity of the adaptor hypothesis' prediction at this time, but merely state that, this prediction notwithstanding, the question of "why codon assignments" is currently unanswered and therefore remains of prime interest. The main reason for determining the set of codon assignments, or "codon catalogue," is that a knowledge of it may shed some light upon the mechanisms behind these particular assignments. While it is unlikely that this approach will tell exactly what mechanisms are involved here, the approach should be of use in answering the initial question of whether there really is an order, a logic, to the codon catalogue, and then perhaps in giving some indication of where to look for the basis of such a logic. At present the codon catalogue is nearly complete, due to the recent techniques developed to determine absolute nucleotide order within codons.2 Thus we are now in a position to investigate the constraints in the codon catalogue. Table 1 presents the (ordered) codon catalogue as determined by Nirenberg and co-workers.2 It is immediately apparent that the catalogue possesses a high degree of order. The most obvious order is in the grouping of codons assigned to the same amino acid. Changing one nucleotide to another -particularly U to C or A to G-in the third position of the triplet in many or possibly all cases leaves the amino acid assignment unchanged. This type of order verifies the general prediction made some time ago on theoretical grounds, that the genetic code has specific degeneracies (equivalences of nucleotides) confined to particular positions in the codon. ' At that time it was also conjectured that such an order, logic, could result from either of two mechanisms: (1) it could be a manifestation of an interaction between an amino acid and some nucleotide grouping (related simply to the codon), either in one or more of the translation steps, or possibly existing at some earlier stage in evolution-a "codon-amino acid" logic, or (2) it could manifest