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 options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Neutral drifts boost enzyme evolvability.

References

  1. 1

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

    CAS  Article  Google Scholar 

  2. 2

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

    CAS  Article  Google Scholar 

  3. 3

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

    CAS  Article  Google Scholar 

  4. 4

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

    CAS  Article  Google Scholar 

  5. 5

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

    CAS  Article  Google Scholar 

  6. 6

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

    CAS  Article  Google Scholar 

  7. 7

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

    CAS  Article  Google Scholar 

  8. 8

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

    CAS  Article  Google Scholar 

  9. 9

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

    CAS  Article  Google Scholar 

  10. 10

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

    CAS  Article  Google Scholar 

  11. 11

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

    CAS  Article  Google Scholar 

  12. 12

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

    CAS  Article  Google Scholar 

  13. 13

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

    CAS  Article  Google Scholar 

  14. 14

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

    Book  Google Scholar 

  15. 15

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

    CAS  Article  Google Scholar 

  16. 16

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

    CAS  Article  Google Scholar 

  17. 17

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

    CAS  Article  Google Scholar 

  18. 18

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

    CAS  Article  Google Scholar 

  19. 19

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

    CAS  Article  Google Scholar 

  20. 20

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

    Google Scholar 

  21. 21

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

    CAS  Article  Google Scholar 

  22. 22

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

    CAS  Article  Google Scholar 

  23. 23

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

    CAS  Article  Google Scholar 

  24. 24

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

    CAS  Article  Google Scholar 

  25. 25

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

    CAS  Article  Google Scholar 

  26. 26

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

    CAS  Article  Google Scholar 

  27. 27

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

    CAS  Article  Google Scholar 

  28. 28

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

    CAS  Article  Google Scholar 

  29. 29

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

  30. 30

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

    Article  Google Scholar 

  31. 31

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

    Article  Google Scholar 

  32. 32

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

    CAS  Article  Google Scholar 

  33. 33

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

    CAS  Article  Google Scholar 

  34. 34

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

    CAS  Article  Google Scholar 

  35. 35

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

    CAS  Article  Google Scholar 

  36. 36

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

    CAS  Article  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

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

Further reading

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