Self-replication of complementary nucleotide-based oligomers

Abstract

THE development of non-enzymatic self-replicating systems based on autocatalytic template-directed reactions is a current objective of bioorganic chemistry^1–6. Typically, a self-complementary template molecule AB is synthesized autocatalytically from two complementary template fragments A and B^7–16. Natural replication of nucleic acids, however, utilizes complementary rather than self-complementary strands. Here we report on a minimal implementation of this type of replication¹⁷ based on cross-catalytic template-directed syntheses of hexadeoxy nucleotide derivatives from amino-trideoxynucleotides. In our experiments, two self-complementary and two complementary templates compete for their combinatorial synthesis from four common trimeric precursors. We provide kinetic evidence that cross-catalytic self-replication of complementary templates can proceed with an efficiency similar to that of autocatalytic self-replication of self-complementary templates. We observe selective stimulation of template synthesis, and thus information transfer, on seeding the reaction mixtures with one of four chemically labelled templates bearing the sequence of the reaction products. Our results bring a stage closer the development of schemes that might explain how replicating systems based on nucleic acids arose on the prebiotic Earth.