The virtual circular genome model for primordial RNA replication
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Updated: Dec 6, 2025

Bacterial Artificial Chromosomes: A Functional Genomics Tool for the Study of Positive-strand RNA Viruses
Published on: December 29, 2015
Lijun Zhou1,2, Dian Ding1,3, Jack W Szostak1,2,3
1Howard Hughes Medical Institute, Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Abstract:
We propose a model for the replication of primordial protocell genomes that builds upon recent advances in the nonenzymatic copying of RNA. We suggest that the original genomes consisted of collections of oligonucleotides beginning and ending at all possible positions on both strands of one or more virtual circular sequences. Replication is driven by feeding with activated monomers and by the activation of monomers and oligonucleotides in situ. A fraction of the annealed configurations of the protocellular oligonucleotides would allow for template-directed oligonucleotide growth by primer extension or ligation. Rearrangements of these annealed configurations, driven either by environmental fluctuations or occurring spontaneously, would allow for continued oligonucleotide elongation. Assuming that shorter oligonucleotides were more abundant than longer ones, replication of the entire genome could occur by the growth of all oligonucleotides by as little as one nucleotide on average. We consider possible scenarios that could have given rise to such protocell genomes, as well as potential routes to the emergence of catalytically active ribozymes and thus the more complex cells of the RNA World.
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