Abstract

DNA and RNA are uniquely suited to be the information storage and propagation molecules in biology. It is unclear, however, whether they are the only solutions available or are simply successful answers for heredity and evolution. To conclusively address questions on the uniqueness of DNA and RNA as genetic material, we have used synthetic chemistry, protein design and directed evolution to develop a new genetic system based on 1,5 anhydrohexitol nucleic acids (HNA), a nucleic acid architecture not found in nature. Thermostable archaeal DNA -dependent DNA polymerases were used as the starting point to develop a two polymerase system that allows efficient transfer of genetic information from DNA into HNA and back into DNA with an aggregate fidelity comparable to RNA virus replication. The HNA system provides a foundational technology for a new field of “synthetic genetics” concerned with the exploration of the sequence and phenotypic space of unnatural genetic biopolymers.