The search for missing links between self-replicating nucleic acids and the RNA world.

The notion that modern metabolism was derived from a complex 'RNA world' in which most reactions were catalyzed by ribozymes has received wide acceptance. However, the evolutionary links between the first self-replicating systems and ribozymes as complex as, say, the Group I self-splicing intron or the HDV ribozyme, have remained elusive. While prebiotic chemists have succeeded in synthesizing short oligonucleotides, it is not immediately obvious how these could have replicated and evolved to the point where they could assume complex shapes and catalytic functions. Nonetheless, recent experiments from a variety of disciplines suggest a plausible pathway from prebiotic chemistry to complex metabolism, and this review is intended as a hypothetical roadmap for the origin and subsequent evolution of life.