Prebiotic synthesis of 5-substituted uracils: a bridge between the RNA world and the DNA-protein world.

Under prebiotic conditions, formaldehyde adds to uracil at the C-5 position to produce 5-hydroxymethyluracil with favorable rates and equilibria. Hydroxymethyluracil adds a variety of nucleophiles, such as ammonia, glycine, guanidine, hydrogen sulfide, hydrogen cyanide, imidazole, indole, and phenol, to give 5-substituted uracils with the side chains of most of the 20 amino acids in proteins. These reactions are sufficiently robust that, if uracil had been present on the primitive Earth, then these substituted uracils would also have been present. The ribozymes of the RNA world would have included many of the functional groups found in proteins today, and their catalytic activities may have been considerably greater than presently assumed.

Nucleic acid analogues and the origins of replication.

Recent interest in the properties of "nucleic acid-like structures" has been stimulated by difficulties encountered in the synthesis and nonenzymatic oligomerization of nucleotides. However, none of the newly proposed monomers has yet been synthesized in a plausibly prebiotic manner. Arguments are presented that analogues based on 8-hydroxymethyladenine and 5-hydroxymethyluracil are promising candidates for primitive nucleotide precursors.