Computational biochemical study of the prebiotic selection of nucleic acids

Abstract

This thesis addresses fundamental questions related to the prebiotic evolutionary selection of the building blocks of nucleic acids. The structural tendencies and propensities in today’s nucleic acids are rationalized based on thermodynamics as a principal driver of evolutionary selection. The free energies of the possible reaction paths available to prebiotic Nature are calculated from quantum chemistry. As one example (of many), the β-anomers of the nucleosides(tides) - predominant in modern nucleic acids - are found to be slightly more stable than their α-counterparts. This small thermodynamic advantage operating over millennia may have contributed to the observed dominance of today’s canonical forms. Calculations also suggest the possibility that non-canonical N-(2-aminoethyl)glycine (AEG) and glycerol nucleosides(tides) may have assisted in the synthesis of today’s nucleosides(tides) if the prebiotic environment has been aqueous. Energetic comparisons of ancestral nucleic acids containing arsenate instead of phosphate indicate no thermodynamic advantage for the phosphate, raising an important open question as to the reason for Nature’s selection of the latter. It is also found, computationally, that barbituric acid may have well been a prebiotic precursor of today’s nucleobases reinforcing earlier proposals. A more fundamental question may be about the choice of nucleic acids as the carriers of genetic information, in the first place, instead of other contenders such as proteins. A partial answer is formulated by proposing a quantitative account of the “<i>value</i>” of information as a new dimension to be added to the traditional “<i>amount</i>” (bits) in Shannon’s information theory. Thus, the thesis addresses certain aspects of evolutionary biochemistry from the standpoint of thermodynamics under differing conditions of solvation. Meanwhile, the rates (kinetics) were not considered in this work since the synthetic and mechanistic steps from reactants to products of most of the proposed reactions remain largely unknown. Several other potential factors have not been considered but, with these variables being constant, our results remain valid and so are the questions they open for future investigations.