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Project Progress

The discovery of catalytic RNA led to the proposal of an RNA World in which RNA provided not only genetic material, but also catalysts. However, the process by which the RNA World emerged remains a mystery. Much discussion has centered on the question of whether genes or metabolism arose first, a problem frequently likened to the classic puzzle of whether chickens or eggs arose first. The puzzle stems from the recognition that genes, whether constructed of DNA or RNA, could not have emerged without an underlying metabolism that supplied the necessary building blocks, and the seemingly contradictory assumption that metabolism could not have emerged without macromolecular catalysts encoded by genes. Framing the problem in this way obscures what is likely to be the correct answer – that genes and metabolism emerged together.

Shelley Copley (University of Colorado at Boulder), with collaborators Eric Smith (Santa Fe Institute), and Harold Morowitz (George Mason University), has been working on a mechanism by which proto-metabolic reaction networks led, perhaps inexorably, to the emergence of RNA as the dominant macromolecule that supplied both catalysis and genetic information. We have proposed a mechanism by which mutual catalysis in proto-metabolic reaction networks led, perhaps inexorably, to the emergence of RNA as the dominant macromolecule that supplied both catalysis and genetic information. An important feature of our model is that selection favored communities of molecules that collectively were best able to catalyze synthesis of their own constituents. Self-replication is viewed as a property of a metabolic network, rather than a property of individual molecules. We suggest that large RNA catalysts emerged beginning from a stage in which catalysis was performed by small molecules such as nucleotides, amino acids, and simple cofactors. Such catalysts would have been inefficient but critical for channeling the flux of organic molecules through productive pathways, as well as for accelerating the rates of reactions. Collections of catalysts that were able to increase the levels of monomeric building blocks would have favored formation of longer oligonucleotides and peptides, but only the oligonucleotides could have been replicated in a template-directed fashion. Thus, the system would have moved toward a collection of RNA catalysts that produced both the nucleotides necessary for their own replication, and the amino acids and cofactors that could not be replicated directly, but that contributed to catalytic processes. These ideas build upon theoretical studies of the properties of self-sustaining and autocatalytic sets of molecules by providing an explicit consideration of molecular reactivity and catalytic mechanisms. A manuscript describing this model is in press in Bioorganic Chemistry.