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:

Lethality and centrality in protein networks

The most highly connected proteins in the cell are the most important for its survival.


Proteins are traditionally identified on the basis of their individual actions as catalysts, signalling molecules, or building blocks in cells and microorganisms. But our post-genomic view is expanding the protein's role into an element in a network of protein–protein interactions as well, in which it has a contextual or cellular function within functional modules1,2. Here we provide quantitative support for this idea by demonstrating that the phenotypic consequence of a single gene deletion in the yeast Saccharomyces cerevisiae is affected to a large extent by the topological position of its protein product in the complex hierarchical web of molecular interactions.

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: Characteristics of the yeast proteome.

Similar content being viewed by others


  1. Hartwell, L. H., Hopfield, J. J., Leibler, S. & Murray, A. W. Nature 402, 47–52 (1999).

    Article  Google Scholar 

  2. Eisenberg, D., Marcotte, E. M., Xenarios, I. & Yeates, T. O. Nature 405, 823–826 (2000).

    Article  CAS  Google Scholar 

  3. Uetz, P. et al. Nature 403, 623–627 (2000).

    Article  ADS  CAS  Google Scholar 

  4. Xenarios, I. et al. Nucleic Acids Res. 28, 289–291 (2000).

    Article  CAS  Google Scholar 

  5. Jeong, H., Tombor, B., Albert, R., Oltvai, Z. N. & Barabási, A.-L Nature 407, 651–654 (2000).

    Article  ADS  CAS  Google Scholar 

  6. Amaral, L. A., Scala, A., Barthelemy, M. & Stanley, H. E. Proc. Natl Acad. Sci. USA 97, 11149–11152 (2000).

    Article  ADS  CAS  Google Scholar 

  7. Rain, J.-C et al. Nature 409, 211–215 (2001).

    Article  ADS  CAS  Google Scholar 

  8. Albert, R., Jeong, H. & Barabási, A.-L Nature 406, 378–382 (2000).

    Article  ADS  CAS  Google Scholar 

  9. Winzeler, E. A. et al. Science 285, 901–906 (1999).

    Article  CAS  Google Scholar 

  10. Ross-Macdonald, P. et al. Nature 402, 413–418 (1999).

    Article  ADS  CAS  Google Scholar 

  11. Fell, D. A. & Wagner, A. in Animating the Cellular Map (eds Hofmeyr, J.-H, Rohwer, J. M. & Snoep, J. L.) 79–85 (Stellenbosch Univ. Press, 2000).

    Google Scholar 

  12. Wagner, A. Nature Genet. 24, 355–361 (2000).

    Article  CAS  Google Scholar 

  13. Costanzo, M. C. et al. Nucleic Acids Res. 28, 73–76 (2000).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding authors

Correspondence to A.-L. Barabási or Z. N. Oltvai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jeong, H., Mason, S., Barabási, AL. et al. Lethality and centrality in protein networks. Nature 411, 41–42 (2001).

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