Replicating DNA Differently

The replication reaction provides the molecular source for mutation, selection and evolution in biology. This reaction also requires two additional stages, transcription and translation, functioning cooperatively, to construct the materials necessary to transfer the genome accurately to progeny. These three stages together constitute biologys Central Dogma, a term that highlights their presence in all autonomous replicating organisms. The template-directed synthesis that underpins each of these stages is dependent on molecular complementarity and the energies of self-assembly, suggesting it might now be possible to borrow from the structural tool set of biology to explore, diversify and even extend these reactions into different structural skeletons. Here we demonstrate, using simple ligation reactions, that it is conceptually possible to simplify the Central Dogma to a two-stage DNA replication process. Through this system DNA sequence information can be read into different molecular skeletons, skeletons with unique catalytic properties, that when extended, are amenable to mutation, selection, and evolution of desired function.