THE PROBABLE SEQUENCE OF NUCLEOTIDES IN SOME CODONS.

Abstract

Proposals arranging the order of nucleotides in the triplets which code for amlino acidsl'-3 have heretofore depended solely upon amino acid replacement data, excepting only the tenuous proposal that AUU and GUU may be the ordered codons for tyrosine and cysteine, respectively. It is obvious, however, that even if we had knowledge of all possible amino acid replacements, we could still write down six internally consistent sets of codons, each set being convertible to another set by some simple algebraic rule (e.g., reverse the order of nucleotides in all codons, or interchange all first nucleotides with the second). The final solution to the order of nucleotides in the codons will undoubtedly have to await the chemical synthesis of ordered polynucleotides, but the work of Gatlin and Davis4 indicates that another means may be available to determine the nucleotide order for some codons. They observed in a group of four organisms that as the lysine content increased, so also did the frequency of doublet nucleotides containing A and T. This result is consistent with the known codon composition of lysine. They did not possess sufficient data to go beyond this conclusion, but it is apparent that if sufficient data were at hand, one might actually be able to correlate the specifically ordered nucleotide doublets with specific amino acids. The chief reservation results from the many potential sources of noise in the system, and one cannot be sure beforehand that one can discriminate the looked-for effect from that noise. On the assumption that one could, however, data were collected on the total protein composition of several organisms for which the doublet nucleotide frequency had already been determined by Josse et al.' and Swartz et al.6 The correspondence between the two parameters was tested for statistical significance, and 26 associations between ordered doublets and specific amino acids were found which were positively correlated at a 95 per cent or better level of confidence.