Skip to main content

Thank you for visiting nature.com. 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.

Protein engineers turned evolutionists

When generating novel tailor-made proteins, protein engineers routinely apply the principles of 'Darwinian' evolution. However, laboratory evolution of proteins also has the potential to test evolutionary theories and reproduce evolutionary scenarios, thus reconstructing putative protein intermediates and providing a glimpse of 'protein fossils'. This commentary describes research at the interface of applied and fundamental molecular evolution, and provides a personal view of how synergy between fundamental and applied experiments indicates novel and more efficient ways of generating new proteins in the laboratory.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Neutral drifts boost enzyme evolvability.

References

  1. Brannigan, J.A. & Wilkinson, A.J. Nat. Rev. Mol. Cell Biol. 3, 964–970 (2002).

    Article  CAS  Google Scholar 

  2. Wang, X., Minasov, G. & Shoichet, B.K. J. Mol. Biol. 320, 85–95 (2002).

    Article  CAS  Google Scholar 

  3. Bershtein, S., Segal, M., Bekerman, R., Tokuriki, N. & Tawfik, D.S. Nature 444, 929–932 (2006).

    Article  CAS  Google Scholar 

  4. Brown, J.E., Brown, P.R. & Clarke, P.H. J. Gen. Microbiol. 57, 273–285 (1969).

    Article  CAS  Google Scholar 

  5. Hall, B.G. FEMS Microbiol. Lett. 174, 1–8 (1999).

    Article  CAS  Google Scholar 

  6. Arnold, F.H., Wintrode, P.L., Miyazaki, K. & Gershenson, A. Trends Biochem. Sci. 26, 100–106 (2001).

    Article  CAS  Google Scholar 

  7. James, L.C., Roversi, P. & Tawfik, D.S. Science 299, 1362–1367 (2003).

    Article  CAS  Google Scholar 

  8. Jensen, R.A. Annu. Rev. Microbiol. 30, 409–425 (1976).

    Article  CAS  Google Scholar 

  9. O'Brien, P.J. & Herschlag, D. Chem. Biol. 6, R91–R105 (1999).

    Article  CAS  Google Scholar 

  10. Afriat, L., Roodveldt, C., Manco, G. & Tawfik, D.S. Biochemistry 45, 13677–13686 (2006).

    Article  CAS  Google Scholar 

  11. Glasner, M.E., Gerlt, J.A. & Babbitt, P.C. Curr. Opin. Chem. Biol. 10, 492–497 (2006).

    Article  CAS  Google Scholar 

  12. Aharoni, A. et al. Nat. Genet. 37, 73–76 (2005).

    Article  CAS  Google Scholar 

  13. Park, H.S. et al. Science 311, 535–538 (2006).

    Article  CAS  Google Scholar 

  14. Piatigorsky, J. Gene sharing and evolution (Harvard University Press, Boston, 2007).

    Book  Google Scholar 

  15. Matsumura, I. & Ellington, A.D. J. Mol. Biol. 305, 331–339 (2001).

    Article  CAS  Google Scholar 

  16. Wouters, M.A., Liu, K., Riek, P. & Husain, A. Mol. Cell 12, 343–354 (2003).

    Article  CAS  Google Scholar 

  17. Tawfik, D.S. Science 311, 475–476 (2006).

    Article  CAS  Google Scholar 

  18. Varadarajan, N., Gam, J., Olsen, M.J., Georgiou, G. & Iverson, B.L. Proc. Natl. Acad. Sci. USA 102, 6855–6860 (2005).

    Article  CAS  Google Scholar 

  19. Collins, C.H., Leadbetter, J.R. & Arnold, F.H. Nat. Biotechnol. 24, 708–712 (2006).

    Article  CAS  Google Scholar 

  20. Graur, D. & Li, W-H . Fundamentals of Molecular Evolution (University of Chicago Press, Chicago, 2000).

    Google Scholar 

  21. Dean, A.M. & Thornton, J.W. Nat. Rev. Genet. 8, 675–688 (2007).

    Article  CAS  Google Scholar 

  22. de Bono, S., Riechmann, L., Girard, E., Williams, R.L. & Winter, G. Proc. Natl. Acad. Sci. USA 102, 1396–1401 (2005).

    Article  CAS  Google Scholar 

  23. Yadid, I. & Tawfik, D.S. J. Mol. Biol. 365, 10–17 (2007).

    Article  CAS  Google Scholar 

  24. Koonin, E.V., Wolf, Y.I. & Karev, G.P. Nature 420, 218–223 (2002).

    Article  CAS  Google Scholar 

  25. Peisajovich, S.G., Rockah, L. & Tawfik, D.S. Nat. Genet. 38, 168–174 (2006).

    Article  CAS  Google Scholar 

  26. Pisarchik, A., Petri, R. & Schmidt-Dannert, C. Protein Eng. Des. Sel. 20, 257–265 (2007).

    Article  CAS  Google Scholar 

  27. Qian, Z. & Lutz, S. J. Am. Chem. Soc. 127, 13466–13467 (2005).

    Article  CAS  Google Scholar 

  28. Amitai, G., Devi-Gupta, R. & Tawfik, D.S. HFSP J. 1, 67–78 (2007).

    Article  CAS  Google Scholar 

  29. Bershtein, S. & Tawfik, D.S. (submitted).

  30. Bloom, J.D., Romero, P.A., Lu, Z. & Arnold, F.H. Biol. Direct 2, 17 (2007).

    Article  Google Scholar 

  31. Bloom, J.D. et al. BMC Biol. 5, 29 (2007).

    Article  Google Scholar 

  32. Kimura, M. Phil. Trans. R. Soc. Lond. B 312, 343–354 (1986).

    Article  CAS  Google Scholar 

  33. van Nimwegen, E., Crutchfield, J.P. & Huynen, M. Proc. Natl. Acad. Sci. USA 96, 9716–9720 (1999).

    Article  CAS  Google Scholar 

  34. Lehmann, M. et al. Protein Eng. 15, 403–411 (2002).

    Article  CAS  Google Scholar 

  35. Watanabe, K., Ohkuri, T., Yokobori, S. & Yamagishi, A. J. Mol. Biol. 355, 664–674 (2006).

    Article  CAS  Google Scholar 

  36. Bloom, J.D., Labthavikul, S.T., Otey, C.R. & Arnold, F.H. Proc. Natl. Acad. Sci. USA 103, 5869–5874 (2006)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This brief and very personal commentary addresses the interface between protein engineering and fundamental molecular evolution. The reference list is therefore rather subjective, and we apologize for not citing a myriad of interesting and relevant work. Research Grants by the Israel Science Foundation and the Estate of Fannie Sherr are gratefully acknowledged. S.G.P. was the recipient of a D. Stone Postdoctoral Fellowship from the Feinberg Graduate School.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peisajovich, S., Tawfik, D. Protein engineers turned evolutionists. Nat Methods 4, 991–994 (2007). https://doi.org/10.1038/nmeth1207-991

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth1207-991

This article is cited by

Search

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