The fidelity of template-directed oligonucleotide ligation and the inevitability of polymerase function

The first living systems may have employed template-directed oligonucleotid e ligation for replication. The utility of oligonucleotide ligation as a me chanism for the origin and evolution of life is in part dependent on its fi delity. We have devised a method for evaluating ligation fidelity in which ligation substrates are selected from random sequence libraries. The fideli ties of chemical and enzymatic ligation are compared under a variety of con ditions. While reaction conditions can be found that promote high fidelity copying, departure from these conditions leads to error-prone copying. In p articular, ligation reactions with shorter oligonucleotide substrates are l ess efficient but more faithful. These results support a model for origins in which there was selective pressure for template-directed oligonucleotide ligation to be gradually supplanted by mononucleotide polymerization.