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Expanding the Genetic Code: Unnatural Base Pairs in Biological Systems

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Abstract

The genetic code is considered to use five nucleic bases (adenine, guanine, cytosine, thymine and uracil), which form two pairs for encoding information in DNA and two pairs for encoding information in RNA. Nevertheless, in recent years several artificial base pairs have been developed in attempts to expand the genetic code. Employment of these additional base pairs increases the information capacity and variety of DNA sequences, and provides a platform for the site-specific, enzymatic incorporation of extra functional components into DNA and RNA. As a result, of the development of such expanded systems, many artificial base pairs have been synthesized and tested under various conditions. Following many stages of enhancement, unnatural base pairs have been modified to eliminate their weak points, qualifying them for specific research needs. Moreover, the first attempts to create a semi-synthetic organism containing DNA with unnatural base pairs seem to have been successful. This further extends the possible applications of these kinds of pairs. Herein, we describe the most significant qualities of unnatural base pairs and their actual applications.

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ACKNOWLEDGMENTS

We would like to thank our co-workers and members of the Alkalaeva lab for participating in discussions about the topics covered in this essay.

Funding

This work was supported by the Russian Foundation for Basic Research (RFBR) (research project grant number 18-29-08044).

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia

    S. A. Mukba, E. Y. Shuvalova, T. V. Egorova & E. Z. Alkalaeva

  2. Faculty of Physics, Moscow State University, 119992, Moscow, Russia

    S. A. Mukba

  3. Skolkovo Institute of Science and Technology, 121205, Skolkovo, Moscow oblast, Russia

    S. A. Mukba

  4. Institute of Science and Technology, 3400, Klosterneuburg, Vienna, Austria

    P. K. Vlasov

  5. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485, Moscow, Russia

    P. M. Kolosov

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  1. S. A. Mukba
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  2. P. K. Vlasov
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  3. P. M. Kolosov
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  4. E. Y. Shuvalova
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  5. T. V. Egorova
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  6. E. Z. Alkalaeva
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Correspondence to E. Z. Alkalaeva.

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Mukba, S.A., Vlasov, P.K., Kolosov, P.M. et al. Expanding the Genetic Code: Unnatural Base Pairs in Biological Systems. Mol Biol 54, 475–484 (2020). https://doi.org/10.1134/S0026893320040111

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