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.

Evidence for co-evolution of gene order and recombination rate

Nature Genetics volume 33, pages 392–395 (2003)Cite this article

Abstract

There is increasing evidence in eukaryotic genomes that gene order is not random, even allowing for tandem duplication. Notably, in numerous genomes1,2,3,4,5,6, genes of similar expression tend to be clustered. Are there other reasons for clustering of functionally similar genes? If genes are linked to enable genetic, rather than physical clustering, then we also expect that clusters of certain genes might be associated with blocks of reduced recombination rates. Here we show that, in yeast, essential genes are highly clustered and this clustering is independent of clustering of co-expressed genes and of tandem duplications. Adjacent pairs of essential genes are preferentially conserved through evolution. Notably, we also find that clusters of essential genes are in regions of low recombination and that larger clusters have lower recombination rates. These results suggest that selection acts to modify both the fine-scale intragenomic variation in the recombination rate and the distribution of genes and provide evidence for co-evolution of gene order and recombination rate.

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

Learn more

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

Figure 1: The difference between real and randomized data in the frequencies of blocks of ten genes with x number of essential genes.
Figure 2: The number of occurrences of essential genes having a downstream essential gene y genes away, along the yeast genome.
Figure 3: Sliding-window plot of the number of essential genes (black line) and standard deviation from chromosomal mean recombination rate (gray line) along chromosome 9.
Figure 4: Recombination rate of non-essential genes as a function of the number of essential genes nearby.

References

  1. Cohen, B.A., Mitra, R.D., Hughes, J.D. & Church, G.M. A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression. Nat. Genet. 26, 183–186 (2000).

    Article  CAS  PubMed  Google Scholar 

  2. Lercher, M.J., Urrutia, A.O. & Hurst, L.D. Clustering of housekeeping genes provides a unified model of gene order in the human genome. Nat. Genet. 31, 180–183 (2002).

    Article  CAS  PubMed  Google Scholar 

  3. Blumenthal, T. et al. A global analysis of Caenorhabditis elegans operons. Nature 417, 851–854 (2002).

    Article  CAS  PubMed  Google Scholar 

  4. Spellman, P.T. & Rubin, G.M. Evidence for large domains of similarly expressed genes in the Drosophila genome. J. Biol. 1, 5 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lercher, M.J., Blumenthal, T. & Hurst, L.D. Co-expression of neighbouring genes in Caenorhabditis elegans is mostly due to operons and duplicate genes. Genome Res. (in the press).

  6. Florens, L. et al. A proteomic view of the Plasmodium falciparum life cycle. Nature 419, 520–526 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. Seoighe, C. et al. Prevalence of small inversions in yeast gene order evolution. Proc. Natl. Acad. Sci. USA 97, 14433–14437 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hurst, L.D., Williams, E.J. & Pal, C. Natural selection promotes the conservation of linkage of co-expressed genes. Trends Genet. 18, 604–606 (2002).

    Article  CAS  PubMed  Google Scholar 

  9. Nei, M. Evolutionary change in linkage intensity. Nature 218, 1160–1161 (1968).

    Article  CAS  PubMed  Google Scholar 

  10. Gerton, J.L. et al. Inaugural article: global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 97, 11383–11390 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Nei, M. Modification of linkage intensity by natural selection. Genetics 57, 625–641 (1967).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Jeffreys, A.J., Kauppi, L. & Neumann, R. Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex. Nat. Genet. 29, 217–222 (2001).

    Article  CAS  PubMed  Google Scholar 

  13. Strathern, J.N., Shafer, B.K. & McGill, C.B. DNA-synthesis errors associated with double-strand-break repair. Genetics 140, 965–972 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Cox, E.C. On the organization of higher chromosomes. Nature 92, 133–134 (1972).

    Google Scholar 

  15. Hirsh, A.E. & Fraser, H.B. Protein dispensability and rate of evolution. Nature 411, 1046–1049 (2001).

    Article  CAS  PubMed  Google Scholar 

  16. Gessler, D.D. & Xu, S. On the evolution of recombination and meiosis. Genet. Res. 73, 119–131 (1999).

    Article  CAS  PubMed  Google Scholar 

  17. Strathern, J.N., Jones, E.W. & Broach, J.R. The molecular biology of the yeast Saccharomyces life cycle and inheritance. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1981).

    Google Scholar 

  18. Dickinson, J.R. & Schweizer, M. The metabolism and molecular physiology of Saccharomyces cerevisiae. (Taylor and Francis, London, 1999).

    Google Scholar 

  19. Mortimer, R.K., Romano, P., Suzzi, G. & Polsinelli, M. Genome renewal: a new phenomenon revealed from a genetic study of 43 strains of Saccharomyces cerevisiae derived from natural fermentation of grape musts. Yeast 10, 1543–1552 (1994).

    Article  CAS  PubMed  Google Scholar 

  20. Cooper, D.N. Human Gene Evolution (BIOS Scientific Publishers Limited, Oxford, UK, 1999).

    Google Scholar 

  21. Fraser, A.G. et al. Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408, 325–330 (2000).

    Article  CAS  PubMed  Google Scholar 

  22. Ball, C.A. et al. Saccharomyces Genome Database provides tools to survey gene expression and functional analysis data. Nucleic Acids Res. 29, 80–81 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Costanzo, M.C. et al. YPD, PombePD and WormPD: model organism volumes of the BioKnowledge library, an integrated resource for protein information. Nucleic Acids Res. 29, 75–79 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Stein, L., Sternberg, P., Durbin, R., Thierry-Mieg, J. & Spieth, J. WormBase: network access to the genome and biology of Caenorhabditis elegans. Nucleic Acids Res. 29, 82–86 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Winzeler, E.A. et al. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285, 901–906 (1999).

    Article  CAS  PubMed  Google Scholar 

  26. Marais, G., Mouchiroud, D. & Duret, L. Does recombination improve selection on codon usage? Lessons from nematode and fly complete genomes. Proc. Natl. Acad. Sci. USA 98, 5688–5692 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Steinmetz, L.M. et al. Systematic screen for human disease genes in yeast. Nat. Genet. 31, 400–404 (2002).

    Article  CAS  PubMed  Google Scholar 

  28. Altschul, S.F. et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank F. Kondrashov and B. Papp for comments on an earlier version of the manuscript. C.P is funded by a Royal Society/Nato visiting fellowship and L.D.H. by the UK Biotechnology and Biosciences Research Council.

Author information

Authors and Affiliations

  1. Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, Somerset, UK

    Csaba Pál & Laurence D. Hurst

  2. Department of Plant Taxonomy and Ecology, Eötvös Loránd University, Pázmány Péter Sétány 1/C, Budapest, H-1117, Hungary

    Csaba Pál

Authors
  1. Csaba Pál
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laurence D. Hurst
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laurence D. Hurst.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Pál, C., Hurst, L. Evidence for co-evolution of gene order and recombination rate. Nat Genet 33, 392–395 (2003). https://doi.org/10.1038/ng1111

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1111

This article is cited by

Search

Advanced 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