Joyce, G.F. & Orgel, L.E.

"Prospects for Understanding the Origin of the RNA World"

The RNA World, Second Edition, 49-77

The general idea that, in the development of life on the earth, evolution based on RNA replication preceded the appearance of protein synthesis was first proposed about 30 years ago (Woese 1967; Crick 1968; Orgel 1968). It was suggested that catalysts made entirely of RNA are likely to have been important at this early stage in the evolution of life, but the possibility that RNA catalysts might still be present in contemporary organisms was overlooked. The unanticipated discovery of ribozymes (Kruger et al. 1982; Guerrier-Takada et al., 1983) initiated extensive discussion of the role of RNA in the origins of lie (Pace and Marsh 1985; Sharp 1985; Lewin 1986) and let to the coining of the phrase "RNA World" (Gilbert 1986).

The RNA World means different things to different authors, so it would be futile to attempt a restrictive definition. All RNA World hypotheses include three basic assumptions: (1) at some time in the evolution of life, genetic continuity was assured by the replication of RNA; (2) Watson-Crick base-pairing was the key to replication; (3) genetically encoded proteins were not involved as catalysts. RNA World hypotheses differ in what they assume about life that may have preceded the RNA World, about the metabolic complexity of the RNA World, and about the role of low-molecular-weight cofactors, possibly including peptides, in the chemistry of the RNA World.

It should be emphasized that the existence of an RNA World as a precursor of our DNA/protein world is a hypothesis. We find it an attractive hypothesis and believe that it derives some support from the results of experiments that it has inspired. The demonstration that the peptide-bond-forming step of protein synthesis is catalyzed by largely protein-free ribosomal RNA is particularly striking (Noller et al. 1992). We recognize, however, that not everyone will find the available evidence compelling.

In our initial discussion of the RNA World we will accept The Molecular Biologist's Dream: "Once upon a time there was a prebiotic pool full of B-D-nucleotides... ." We now consider what would have to have happened to make the dream come true. This discussion triggers The Prebiotic Chemist's Nightmare: how to make any kind of self-replicating system from the intractable mixtures that are formed in experiments designed to simulate the chemistry of the primitive earth.