To Build a Pre-RNA

245 IN ASTROBIOLOGY (Volume 2, Number 4), Cleaves (2002) explored the chemical reaction of nucleic bases to the compound acrolein. This paper reports an important step toward the goal of identifying “pre-RNA,” a prebiotic molecule believed by many to have predated proteins, DNA, and even RNA in the evolution of life on Earth. The RNA World hypothesis states that RNA preceded DNA as the genetic molecule of life and that RNA preceded protein for biocatalysis (Joyce, 1989). The RNA World hypothesis provides a solution to the “chicken and egg problem” presented by modern biochemistry: RNA came before protein synthesis. However, the relationship between the origin of RNA and the origin of life is unclear. In some models RNA (or one of its isomers) formed prebiotically and therefore is the origin of life (e.g., Eschenmoser, 1999; Ferris, 2002). In other models RNA evolved from clay minerals (e.g., Cairns-Smith, 1971, 1982), metabolic cycles on a mineral surface (e.g., Wachtershauser, 1988; Russell et al., 1990; Martin and Russell, 2003), metabolic cycles in a lipid vesicle (e.g., Segre et al., 2001), or a “pre-RNA” organic molecule (e.g., Joyce et al., 1987; Nielsen, 1993). In the latter case, pre-RNA would have been a robustly synthesized, genetic molecule, presumably similar to DNA or RNA. For those who envision a pre-RNA molecule as the precursor to RNA, finding a set of prebiotically plausible reactions that form a nucleic acid-like molecule remains a significant challenge for origin of life research. Assuming that the chemistry of the origin of life will be vigorous and reproducible, those in search of life’s preRNA are often looking for robust chemical reactions of nucleic bases with a suitable pre-RNA organic molecule. Recently, there have been efforts to synthesize prebiotically possible pre-RNAs. For example, Nelson et al. (2000) explored the prebiotic synthesis of peptide nucleic acid (PNA) as a potential pre-RNA. PNA was first developed as a synthetic nucleic acid for hybridization as it forms double helices with RNA or DNA, both of which have a high melting point. While aqueous PNA adopts a similar helical structure as RNA or DNA, it is achiral and noncharged, and lacks a sugar-phosphate backbone (Nielsen et al., 1991). These attributes may be desirable for pre-RNA because the lack of chirality reduces difficulties encountered in prebiotic polymerization (Joyce et al., 1987), and sugar-phosphate backbones may not be prebiotic (Keefe and Miller, 1995; Larralde et al., 1995). Furthermore, Nelson et al. (2000) showed that the components of PNA can be synthesized via the Strecker synthesis in a spark discharge of reduced gases or during the polymerization of ammonium cyanide. While PNA looks promising, other possible pre-RNAs that avoid the prebiotic pitfalls of RNA are being investigated. Instead of beginning with a particular structure (e.g., PNA) and working to synthesize it under plausible prebiotic conditions, Cleaves (2002) began the process of building a pre-RNA one step at a time, exploring likely prebiotic reactions of various nucleic bases. As an important step toward the goal of identifying a prebiotic genetic molecule, Cleaves (2002) explored the addition of nucleic bases to the compound acrolein. Acrolein