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.

  • Brief Communication
  • Published:

Genomic function (communication arising)

Rate of evolution and gene dispensability


Whether more dispensable genes evolve faster than less dispensable ones1 is a contentious issue2,3,4. Comparing yeast and worm genes, Hirsh and Fraser3 observe a gradual tendency for less dispensable genes (those that reduce the growth rate of yeast when knocked out) to have lower rates of protein evolution. Here we repeat their analysis using larger data sets and find no evidence that dispensability explains the variation in rates of protein evolution. Although Hirsh and Fraser provide a model to show why their result is to be expected, our analysis suggests that their model, which assumes among other things that no substitution is advantageous, cannot be generally applied.

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

Access options

Buy this article

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

Figure 1: Relationship between the rate of protein evolution (protein distance, D) and the fitness effect of knockout (F, 1 − dispensability) for genes in a comparison involving a range of yeast species (N = 1,660, Pearson r2FD = 0.00289, P = 0.028, Spearman rank ρ2FD = 0.00515, P = 0.0034).

Similar content being viewed by others


  1. Wilson, A. C., Carlson, S. S. & White, T. J. Annu. Rev. Biochem. 46, 573–639 (1977).

    Article  CAS  PubMed  Google Scholar 

  2. Hurst, L. D. & Smith, N. G. C. Curr. Biol. 9, 747–750 (1999).

    Article  CAS  PubMed  Google Scholar 

  3. Hirsh, A. E. & Fraser, H. B. Nature 411, 1046–1049 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Jordan, I. K., Rogozin, I. B., Wolf, Y. I. & Koonin, E. V. Genome Res. 12, 962–968 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Steinmetz, L. M. et al. Nature Genet. 31, 400–404 (2002).

    Article  CAS  PubMed  Google Scholar 

  6. Pál, C., Papp, B. & Hurst, L. D. Mol. Biol. Evol. 18, 2323–2326 (2001).

    Article  PubMed  Google Scholar 

  7. Yang, Z. Comput. Appl. Biosci. 13, 555–556 (1997).

    CAS  PubMed  Google Scholar 

  8. Holstege, F. C. et al. Cell 95, 717–728 (1998).

    Article  CAS  PubMed  Google Scholar 

  9. Coghlan, A. & Wolfe, K. H. Yeast 16, 1131–1145 (2000).

    Article  CAS  PubMed  Google Scholar 

  10. Fraser, H. B., Hirsh, A. E., Steinmetz, L. M., Scharfe, C. & Feldman, M. W. Science 296, 750–752 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Pál, C., Papp, B. & Hurst, L. D. Genetics 158, 927–931 (2001).

    PubMed  PubMed Central  Google Scholar 

  12. Gibbons, J. D. Nonparametric Measures of Association (ed. Lewis-Beck, M. S.) (Sage, Newbury Park, UK, 1993).

    Book  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Laurence D. Hurst.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pál, C., Papp, B. & Hurst, L. Rate of evolution and gene dispensability. Nature 421, 496–497 (2003).

Download citation

  • 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