DIRECT INTERACTIONS BETWEEN AMINO ACIDS AND NUCLEOTIDES AS A POSSIBLE EXPLANATION FOR THE ORIGIN OF THE GENETIC CODE (PREBIOTIC EVOLUTION)

The origin of nucleic acid-directed protein synthesis system is a critical circumstance in the history of living systems. Despite the fact that molecular mechanisms of the modern protein synthesis system have been known in increasingly detailed terms, our understanding of the history of the genetic code remains poor.; A study of the associations of amino acids and nucleotides was undertaken with a view to establish a possible physical basis for the origin of the codon assignment. The association of homocodonic amino acids (L-Phe, L-Lys, L-Pro, and Gly) and some heterocodonic amino acids (L-Ala, L-Arg, L-Cys, L-Glu, L-Met, and L-Tyr) with various nucleotide sequences (nucleoside 2'-, nucleoside 3'-, or nucleoside 5'-monophosphates; dinucleoside (2'-5')-, or dinucleoside (3'-5') -monophosphates; and trinucleoside (3'-5')-diphosphates) were studied using ('1)H NMR spectroscopy. Association constants for the various interactions were determined by following the changes in the chemical shifts of the anomeric and ring protons of the nucleotide as a function of amino acid concentration and fitting the experimental data to a binding curve. Curve fitting was done using a nonlinear least squares regression analysis program which analyzed the data and returned the best estimates for the association constants along with the statistics of the fit, which included the confidence limits for the association constants, variance, correlation coefficients, and plots of residuals vs. dependent and independent variables.; The strongest associations of all the amino acids investigated were observed with their respective anticodonic nucleotide sequences. The strength of association was seen to increase significantly with increase in the chain length of the anticodonic nucleotide from monomer, dimer through trimer. The association of amino acids with different phosphate esters of nucleosides suggests that a definite isomeric structure of the nucleotide is required for association with an amino acid: the 5'-mononucleotides, and (3'-5') linked dinucleoside monophosphates are the favored geometries for strong associations. The conclusion reached as a result of these studies is that there is a possible anticodonic basis for the origin of the genetic code.