title: Errors and alternatives in prebiotic replication and catalysis.
abstract: The work on nonenzymatic nucleic acid replication performed by Leslie Orgel and co-workers over the last four decades, now extended by work on artificial selection of RNA aptamers and ribozymes, is generating some pessimism concerning the 'naked gene' theories of the origin of life. It is suggested here that the low probability of finding RNA aptamers and ribozymes within pools of random sequences is not as disquieting as the poor gain in efficiency obtained with increases in information content. As acknowledged by Orgel and many other authors, primitive RNA replication and catalysis must have occurred within already complex and dynamic environments. I, thus, propose to pay attention to a number of possibilities that bridge the gap between 'naked gene' theories, on one side, and metabolic theories in which complex systems self-propagate by growth and fragmentation, on the other side. For instance, one can de-emphasize nucleotide-by-nucleotide replication leading to long informational polymers, and view instead long random polymers as storage devices, from which shorter oligomers are excised. Catalytic tasks would be mainly performed by complexes associating two or more oligomers belonging to the same or to different chemical families. It is proposed that the problems of stability, binding affinity, reactivity, and specificity could be easier to handle by heterogeneous complexes of short oligomers than by long, single-stranded polymers. Finally, I point out that replication errors in a primitive replication context should include incorporations of alternative nucleotides with interesting, chemically reactive groups. In this way, an RNA sequence could be at the same time an inert sequence when copied without error, and a ribozyme, when a chemically reactive nucleotide is inadvertently introduced during replication.
authors: Laboratoire de Physique Statistique, Ecole Normale Supérieure, 24 rue Lhomond, F-75231 Paris Cedex 05. jacques.ninio@lps.ens.fr
authors: Jacques
authors: J
authors: Ninio
mesh_terms: D002384:Catalysis; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics; D004261:DNA Replication; D042822:Genomic Instability; D009690:Nucleic Acid Conformation; D000069497:Origin of Life; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D012313:RNA / Q000235:genetics
chemical_list: D011506:Proteins; D012313:RNA; D004247:DNA