Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Toward an orthogonal central dogma

The central dogma processes of DNA replication, transcription, and translation are responsible for the maintenance and expression of every gene in an organism. An orthogonal central dogma may insulate genetic programs from host regulation and allow expansion of the roles of these processes within the cell.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: The orthogonal central dogma concept.
Figure 2: Component orthogonal central dogma systems.


  1. 1

    Ravikumar, A., Arrieta, A. & Liu, C.C. Nat. Chem. Biol. 10, 175–177 (2014).

    CAS  Article  Google Scholar 

  2. 2

    Klassen, R. & Meinhardt, F. in Microbial Linear Plasmids, Microbiology Monographs. Vol. 7, 187226 (Springer, Berlin, Heidelberg, 2007).

  3. 3

    Kranaster, R. & Marx, A. ChemBioChem 11, 2077–2084 (2010).

    CAS  Article  Google Scholar 

  4. 4

    Yu, H., Zhang, S. & Chaput, J.C. Nat. Chem. 4, 183–187 (2012).

    CAS  Article  Google Scholar 

  5. 5

    Pinheiro, V.B. et al. Science 336, 341–344 (2012).

    CAS  Article  Google Scholar 

  6. 6

    Glaser, J.I. et al. PLoS Comput. Biol. 9, e1003145 (2013).

    CAS  Article  Google Scholar 

  7. 7

    Marlière, P. et al. Angew. Chem. Int. Ed. Engl. 50, 7109–7114 (2011).

    Article  Google Scholar 

  8. 8

    Malyshev, D.A. et al. Nature 509, 385–388 (2014).

    CAS  Article  Google Scholar 

  9. 9

    Gowrishankar, J. & Harinarayanan, R. Mol. Microbiol. 54, 598–603 (2004).

    CAS  Article  Google Scholar 

  10. 10

    Guillerez, J., Lopez, P. J., Proux, F., Launay, H. & Dreyfus, M. Proc. Natl. Acad. Sci. USA 102, 5958–5963 (2005).

    CAS  Article  Google Scholar 

  11. 11

    Bonner, G., Lafer, E.M. & Sousa, R. J. Biol. Chem. 269, 25120–25128 (1994).

    CAS  Google Scholar 

  12. 12

    Becskei, A. & Serrano, L. Nature 405, 590–593 (2000).

    CAS  Article  Google Scholar 

  13. 13

    Bleris, L. et al. Mol. Syst. Biol. 7, 519 (2011).

    PubMed  PubMed Central  Google Scholar 

  14. 14

    Shis, D.L. & Bennett, M.R. Proc. Natl. Acad. Sci. USA 110, 5028–5033 (2013).

    CAS  Article  Google Scholar 

  15. 15

    Gaj, T., Gersbach, C.A. & Barbas, C.F. III. Trends Biotechnol. 31, 397–405 (2013).

    CAS  Article  Google Scholar 

  16. 16

    Chin, J.W. Annu. Rev. Biochem. 83, 379–408 (2014).

    CAS  Article  Google Scholar 

  17. 17

    Wang, K. et al. Nat. Chem. 6, 393–403 (2014).

    CAS  Article  Google Scholar 

  18. 18

    Ostrov, N. et al. Science 353, 819–822 (2016).

    CAS  Article  Google Scholar 

  19. 19

    Wang, K. et al. Nature 539, 59–64 (2016).

    CAS  Article  Google Scholar 

  20. 20

    Maini, R. et al. Biochemistry 54, 3694–3706 (2015).

    CAS  Article  Google Scholar 

  21. 21

    Dedkova, L.M. et al. Biochemistry 51, 401–415 (2012).

    CAS  Article  Google Scholar 

  22. 22

    Melo Czekster, C., Robertson, W.E., Walker, A.S., Söll, D. & Schepartz, A. J. Am. Chem. Soc. 138, 5194–5197 (2016).

    CAS  Article  Google Scholar 

  23. 23

    Liu, Y., Kim, D. S. & Jewett, M.C. Curr. Opin. Chem. Biol. 40, 87–94 (2017).

    CAS  Article  Google Scholar 

  24. 24

    Kitahara, K. & Suzuki, T. Mol. Cell 34, 760–766 (2009).

    CAS  Article  Google Scholar 

  25. 25

    Orelle, C. et al. Nature 524, 119–124 (2015).

    CAS  Article  Google Scholar 

  26. 26

    Fried, S.D., Schmied, W.H., Uttamapinant, C. & Chin, J.W. Angew. Chem. Int. Ed. Engl. 54, 12791–12794 (2015).

    CAS  Article  Google Scholar 

  27. 27

    An, W. & Chin, J.W. Proc. Natl. Acad. Sci. USA 106, 8477–8482 (2009).

    CAS  Article  Google Scholar 

  28. 28

    Anger, A.M. et al. Nature 497, 80–85 (2013).

    CAS  Article  Google Scholar 

  29. 29

    Ben-Shem, A. et al. Science 334, 1524–1529 (2011).

    CAS  Article  Google Scholar 

  30. 30

    Neumann, H., Slusarczyk, A.L. & Chin, J.W. J. Am. Chem. Soc. 132, 2142–2144 (2010).

    CAS  Article  Google Scholar 

  31. 31

    Chatterjee, A., Xiao, H. & Schultz, P.G. Proc. Natl. Acad. Sci. USA 109, 14841–14846 (2012).

    CAS  Article  Google Scholar 

  32. 32

    Bernardi, G. Gene 354, 189–200 (2005).

    CAS  Article  Google Scholar 

Download references


We thank members of our group and reviewers for valuable comments. C.C.L. acknowledges the Defense Advanced Research Projects Agency (DARPA-14-49-AS-BRICS-FP-017), the National Institutes of Health (1DP2GM119163-01), and the Arnold and Mabel Beckman Foundation. M.C.J. acknowledges the Army Research Office (W911NF-16-1-0372), the National Science Foundation (MCB-1716766), the Air Force Research Laboratory Center of Excellence (FA8650-15-2-5518), the David and Lucile Packard Foundation, and the Camille-Dreyfus Teacher-Scholar Program. The US Government is authorized to reproduce and distribute reprints for Governmental purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of Air Force Research Laboratory or the US Government. J.W.C. acknowledges the Medical Research Council, UK (MC_U105181009 and MC_UP_A024_1008) and the European Research Council (ERC Advanced Grant (SGCR)). C.A.V. acknowledges the Office of Naval Research Multidisciplinary University Research Initiative (N00014-16-1-2388).

Author information



Corresponding authors

Correspondence to Chang C Liu or Michael C Jewett or Jason W Chin or Chris A Voigt.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Liu, C., Jewett, M., Chin, J. et al. Toward an orthogonal central dogma. Nat Chem Biol 14, 103–106 (2018).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing