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.

Mutational robustness can facilitate adaptation


Robustness seems to be the opposite of evolvability. If phenotypes are robust against mutation, we might expect that a population will have difficulty adapting to an environmental change, as several studies have suggested1,2,3,4. However, other studies contend that robust organisms are more adaptable5,6,7,8. A quantitative understanding of the relationship between robustness and evolvability will help resolve these conflicting reports and will clarify outstanding problems in molecular and experimental evolution, evolutionary developmental biology and protein engineering. Here we demonstrate, using a general population genetics model, that mutational robustness can either impede or facilitate adaptation, depending on the population size, the mutation rate and the structure of the fitness landscape. In particular, neutral diversity in a robust population can accelerate adaptation as long as the number of phenotypes accessible to an individual by mutation is smaller than the total number of phenotypes in the fitness landscape. These results provide a quantitative resolution to a significant ambiguity in evolutionary theory.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: The genotype–phenotype model.
Figure 2: Robustness and adaptation time.
Figure 3: Robustness and diversity.


  1. Ancel, L. W. & Fontana, W. Plasticity, evolvability, and modularity in RNA. J. Exp. Zool. 288, 242–283 (2000)

    Article  CAS  Google Scholar 

  2. Carter, A. J. R., Hermisson, J. & Hansen, T. F. The role of epistatic gene interactions in the response to selection and the evolution of evolvability. Theor. Popul. Biol. 68, 179–196 (2005)

    Article  Google Scholar 

  3. Cowperthwaite, M. C., Economo, E. P., Harcombe, W. R., Miller, E. L. & Meyers, L. A. The ascent of the abundant: how mutational networks constrain evolution. PLoS Comput. Biol. 4, e1000110 (2008)

    Article  ADS  MathSciNet  Google Scholar 

  4. Parter, M., Kashtan, N. & Alon, U. Facilitated variation: how evolution learns from past environments to generalize to new environments. PLoS Comput. Biol. 4, e1000206 (2008)

    Article  ADS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  6. Aldana, M., Balleza, E., Kauffman, S. & Resendiz, O. Robustness and evolvability in genetic regulatory networks. J. Theor. Biol. 245, 433–448 (2007)

    Article  MathSciNet  Google Scholar 

  7. Elena, S. F. & Sanjuan, R. The effect of genetic robustness on evolvability in digital organisms. BMC Evol. Biol. 8, 284 (2008)

    Article  Google Scholar 

  8. McBride, R. C., Ogbunugafor, C. B. & Turner, P. E. Robustness promotes evolvability of thermotolerance in an RNA virus. BMC Evol. Biol. 8, 231 (2008)

    Article  Google Scholar 

  9. de Visser, J. A. G. M. et al. Evolution and detection of genetic robustness. Evolution 57, 1959–1972 (2003)

    PubMed  Google Scholar 

  10. Lenski, R. E., Barrick, J. E. & Ofria, C. Balancing robustness and evolvability. PLoS Biol. 4, e428 (2006)

    Article  Google Scholar 

  11. Wagner, A. Robustness and evolvability: a paradox resolved. Proc. R. Soc. B 275, 91–100 (2008)

    Article  Google Scholar 

  12. Rutherford, S. L. & Lindquist, S. Hsp90 as a capacitor for morphological evolution. Nature 396, 336–342 (1998)

    Article  ADS  CAS  Google Scholar 

  13. Bergman, A. & Siegal, M. L. Evolutionary capacitance as a general feature of complex gene networks. Nature 424, 549–552 (2003)

    Article  ADS  CAS  Google Scholar 

  14. Kirschner, M. & Gerhart, J. The Plausibility of Life: Resolving Darwin’s Dilemma (Yale Univ. Press, 2005)

    Google Scholar 

  15. Wagner, A. Robustness and Evolvability in Living Systems (Princeton Univ. Press, 2005)

    Google Scholar 

  16. Meyers, L., Ancel, F. & Lachmann, M. Evolution of genetic potential. PLoS Comput. Biol. 1, e32 (2005)

    Article  ADS  Google Scholar 

  17. van Nimwegen, E. Influenza escapes immunity along neutral networks. Science 314, 1884–1886 (2006)

    Article  CAS  Google Scholar 

  18. Blount, Z. D., Borland, C. Z. & Lenski, R. E. Historical contingency and the evolution of a key innovation in an experimental population of Escherichia coli . Proc. Natl Acad. Sci. USA 105, 7899–7906 (2008)

    Article  ADS  CAS  Google Scholar 

  19. Fontana, W. & Schuster, P. Continuity in evolution: on the nature of transitions. Science 280, 1451–1455 (1998)

    Article  ADS  CAS  Google Scholar 

  20. Ciliberti, S., Martin, O. C. & Wagner, A. Innovation and robustness in complex regulatory gene networks. Proc. Natl Acad. Sci. USA 104, 13591–13596 (2007)

    Article  ADS  CAS  Google Scholar 

  21. Sumedha, O. C. & Wagner, A. New structural variation in evolutionary searches of RNA neutral networks. Biosystems 90, 475–485 (2007)

    Article  CAS  Google Scholar 

  22. Koelle, K., Cobey, S., Grenfell, B. & Pascual, M. Epochal evolution shapes the phylodynamics of interpandemic influenza a (H3N2) in humans. Science 314, 1898–1903 (2006)

    Article  ADS  CAS  Google Scholar 

  23. Cambray, G. & Mazel, D. Synonymous genes explore different evolutionary landscapes. PLoS Genet. 4, e1000256 (2008)

    Article  Google Scholar 

  24. Isalan, M. et al. Evolvability and hierarchy in rewired bacterial gene networks. Nature 452, 840–845 (2008)

    Article  ADS  CAS  Google Scholar 

  25. van Nimwegen, E., Crutchfield, J. & Huynen, M. Neutral evolution of mutational robustness. Proc. Natl Acad. Sci. USA 96, 9716–9720 (1999)

    Article  ADS  CAS  Google Scholar 

  26. Forster, R., Adami, C. & Wilke, C. O. Selection for mutational robustness in finite populations. J. Theor. Biol. 243, 181–190 (2006)

    Article  MathSciNet  Google Scholar 

  27. Daniels, B. C., Chen, Y.-J., Sethna, J. P., Gutenkunst, R. N. & Myers, C. R. Sloppiness, robustness, and evolvability in systems biology. Curr. Opin. Biotechnol. 19, 389–395 (2008)

    Article  CAS  Google Scholar 

  28. Wilds, R., Kauffman, S. A. & Glass, L. Evolution of complex dynamics. Chaos 18, 033109 (2008)

    Article  ADS  MathSciNet  Google Scholar 

  29. Wilke, C. O., Wang, J. L., Ofria, C., Lenski, R. E. & Adami, C. Evolution of digital organisms at high mutation rates leads to survival of the flattest. Nature 412, 331–333 (2001)

    Article  ADS  CAS  Google Scholar 

  30. Krakauer, D. C. & Plotkin, J. B. Redundancy, antiredundancy, and the robustness of genomes. Proc. Natl Acad. Sci. USA 99, 1405–1409 (2002)

    Article  ADS  CAS  Google Scholar 

Download references


We thank P. Turner and members of the Plotkin laboratory for advice and feedback. J.B.P. acknowledges funding from the Burroughs Wellcome Fund, the David and Lucile Packard Foundation, the James S. McDonnell Foundation, the Alfred P. Sloan Foundation, the Defense Advanced Research Projects Agency (HR0011-05-1-0057) and the US National Institute of Allergy and Infectious Diseases (2U54AI057168). G.P.W. acknowledges funding from the John Templeton Foundation and the Perinatology Research Branch of the US National Institutes of Health.

Author Contributions J.A.D., J.B.P. and G.P.W. designed the project. J.A.D. and J.B.P. wrote the paper; G.P.W. and T.L.P. edited the paper. J.A.D. performed the simulations. T.L.P. performed most of the analysis, with contributions from J.B.P. and J.A.D. J.A.D., T.L.P. and J.B.P. wrote the Supplementary Information.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Joshua B. Plotkin.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Data, Supplementary Figures 1-12 with Legends, Supplementary Table1 and Supplementary References. (PDF 830 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Draghi, J., Parsons, T., Wagner, G. et al. Mutational robustness can facilitate adaptation. Nature 463, 353–355 (2010).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


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