
Furthermore, the rule-based one-to-one pairing of complementary bases in a Watson-Crick duplex ( Fig. 1) provides a robust mechanism for information transfer during replication that could have been operative from the advent of oligonucleotides. The ever-increasing list of processes that involve RNA in contemporary life continues to strengthen this view ( Mandal and Breaker 2004 Gesteland and Atkins 2006). 1983) created widespread interest in an earlier proposal ( Woese 1967 Crick 1968 Orgel 1968) that nucleic acids were the first biopolymers of life, as nucleic acids transmit genetic information and could have once been responsible for catalyzing a wide range of reactions.

The discovery of catalytic RNA molecules in the early 1980s ( Kruger et al. Nevertheless, the requirements for the chemical emergence of life would appear simplified if one polymer was initially able to store and transfer information as well as perform selective chemical catalysis-two essential features of life. However, requiring that these biopolymers appeared strictly sequentially may be an overly restrictive preconception-nucleic acids and noncoded peptides may have arisen independently and only later become dependent on each other.

This mutual dependence has been described as a “chicken-or-the-egg” dilemma concerning which came first. In contemporary life, nucleic acids provide the amino acid sequence information required for protein synthesis, while protein enzymes carry out the catalysis required for nucleic acid synthesis. Here, we consider studies of variations in these three distinct components of nucleic acids with regard to the question: Is RNA, as is generally acknowledged of DNA, the product of evolution? If so, what chemical and structural features might have been more likely and advantageous for a proto-RNA? Experimental investigations, made possible by the application of synthetic and physical organic chemistry, have now provided evidence that the nucleobases (A, G, C, and T/U), the trifunctional moiety (ribose), and the linkage chemistry (phosphate esters) of contemporary nucleic acids may be optimally suited for their present roles-a situation that suggests refinement by evolution.


However, the de novo synthesis of RNA using only plausible prebiotic chemistry has proven difficult, to say the least. The discovery of catalytic RNA molecules subsequently provided support for the hypothesis that RNA was perhaps even the first polymer of life. Since the structure of DNA was elucidated more than 50 years ago, Watson-Crick base pairing has been widely speculated to be the likely mode of both information storage and transfer in the earliest genetic polymers.
