Aspects of Nucleic Acid Structure and Function

Abstract

Despite decades of intense study, certain physico-chemical aspects of the nucleic acids–the genetic repository of life–remain enigmatic. Thus, solutions of DNA are apparently constituted of varying amounts of double and single-stranded forms, with melting studies being inconclusive about the effect of temperature on the composition. Consequently, this casts doubt on current estimates of the thermodynamic stability of the base pairs. However, the overwhelming stability of the Watson-Crick model is adumbrated by a kinetic analysis of the action of DNA polymerase, microscopic reversibility indicating that polymerase action is kinetically controlled, whereas proof reading-excision is thermodynamically controlled. The structural basis for the differing roles played by DNA and RNA in the sustenance and propagation of life also remains to be clarified. It appears that formation of the RNA double helix is sterically inhibited by the 2’ ribose hydroxyl group, which is also relatively inaccessible to external base, thus enhancing hydrolytic stability. The in vivo conformation of RNA is likely determined by the requirements of its appointed biological role, the large size of tRNAs being particularly significant in possibly leading to enhanced specificity in its interaction with the corresponding tRNA synthetase. The proclivity of RNA generally to remain single stranded may indeed be the reason for the existence of viruses as stable RNA-protein complexes. The preeminent role of nucleic acids as “genetic guardians” is, however, blurred by the fact that the translation of the genetic code is contingent on the action of the various tRNA synthetases. This implies that the genetic code is manifested via codon-anticodon specificity only by the involvement of protein molecules that are unique to each codon-anticodon pair. This has intriguing implications for the origin and evolution of the genetic code, possibly indicating that the tRNA synthetases are a relic of prebiotic protein-nucleic acid hybrids (thus also raising doubts about the RNA world hypothesis).