Many current scenarios for the origin of life depend upon the validity of the "RNA World" hypothesis (1). This hypothesis is attractive because it alleviates the long-standing paradox concerning which came first, proteins or nucleic acids. However, experimental support for the spontaneous generation of RNA is far from satisfactory. The nucleotide bases and ribose sugars can be synthesized under what are arguably prebiotic conditions, but a process by which the bases, ribose, and phosphate would have spontaneously assembled into RNA polymers looks increasingly impossible (1). Thus, it appears that some other RNA-like polymer preceded RNA, and eventually evolved into RNA. We have presented a detailed hypothesis for how small molecule intercalation and backbone formation with low-energy covalent bonds could have brought about the first RNA-like polymers (2). We have now demonstrated experimentally that small molecules known to intercalate the bases of RNA and DNA can act as "molecular midwives" and increase the non-enzymatic ligation of short oligonucleotides 1000-fold over the rate observed in the absence of small molecule intercalation (3). It is feasible that similar small molecules on the prebiotic Earth promoted the formation of the first RNA-like polymers. We are also exploring the possibility that low-energy acetal bonds preceded the phosphodiester bonds of RNA. We have recently demonstrated that glyoxylate, an organic mimic of phosphate, spontaneously couples nucleosides into dinucleotides when dried in the presence of divalent metal salts (4). Molecular dynamics studies of model RNA-like duplexes containing glyoxylate-linked nucleosides support our proposal that these nucleic acids would have structural properties similar to present day RNA.

References and Footnotes

1. Gesteland, R. and Atkins, J. F. (Eds.) The RNA World, Second Ed. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press (1999).
2. Hud, N. V. and Anet, F. A. L. J. Theor. Biol. 205, 543-562 (2000).
3. Jain, S. S., Anet, F. A. L., Stahle, C. J., and Hud, N. V. Angew. Chem. Int. Ed. Eng. 43, 2004-2008 (2004).
4. Bean, H. D., Anet, F. A. L., Gould, I. R., and Hud, N. V. Origins Life Evol. B. 36, 39-63 (2006).