Building outside biology: new genetic materials, new tools




   DNA and RNA are the only natural genetic materials in biology and appear uniquely suited for information storage and replication[1]. Systematic modification of their core moieties (nucleobase, sugar and phosphate) has demonstrated that all three contribute to biopolymer function. Nevertheless, it is less clear whether any of those synthetic nucleic acids, or xenobiotic nucleic acids (XNAs), are viable genetic materials -- capable of storing and propagating biological information.

   Biology has evolved a range of specialised enzymes that are capable to accessing and replicating genetic information by the template-dependent synthesis of DNA (and RNA), termed polymerases. Polymerases capable of synthesising XNA from a DNA template (DNA -> XNA) and subsequently retrieving that information back to DNA (XNA -> DNA), demonstrate that a given XNA can be used to store and propagate information and is a bona fide genetic material[2-4].

   However, replicative DNA polymerases are remarkable molecular machines and have long been under evolutionary pressure to maintain the integrity of natural biological information: avoiding the incorporation of RNA or damaged nucleotides, and minimising misincorporations. Consequently, XNA precursors are (in most cases) not efficiently incorporated by natural polymerases.

   Directed evolution is a powerful tool to evolve DNA polymerases and it has been successfully used to demonstrate that at least some XNAs can be made into viable genetic materials[5]. Such synthetic genetic materials highlight that RNA and DNA are not unique chemical solutions for genetic information storage, and that the expansion or the overhaul of the Central Dogma is plausible.



1. Benner, S. A. (2004) Understanding nucleic acids using synthetic chemistry. Acc. Chem. Res. 37, 784--797.
2. Pinheiro, V. B., Taylor, A. I., Cozens, C., Abramov, M., Renders, M., Zhang, S., Chaput, J. C., Wengel, J., Peak-Chew, S.-Y., McLaughlin, S. H., Herdewijn, P., and Holliger, P. (2012) Synthetic Genetic Polymers Capable of Heredity and Evolution. Science (80-. ). 336, 341--344.
3. Pinheiro, V. B., Loakes, D., and Holliger, P. (2013) Synthetic polymers and their potential as genetic materials. BioEssays 35.
4. Pinheiro, V. B., and Holliger, P. (2012) The XNA world: progress towards replication and evolution of synthetic genetic polymers. Curr Opin Chem Biol 16, 245--252.
5. Tizei, P. A. G., Csibra, E., Torres, L., and Pinheiro, V. B. (2016) Selection platforms for directed evolution in synthetic biology. Biochem. Soc. Trans. 44, 1165--1175.