Bioinformatics pp 181-199 | Cite as

Inferring Functional Relationships from Conservation of Gene Order

  • Gabriel Moreno-Hagelsieb
Part of the Methods in Molecular Biology™ book series (MIMB, volume 453)


The idea behind the gene neighbor method is that conservation of gene order in evolutionarily distant prokaryotes indicates functional association. The procedure presented here starts with the organization of all the genomes into pairs of adjacent genes. Then, pairs of genes in a genome of interest are mapped to their corresponding orthologs in other, informative, genomes. The final step is to determine whether the orthologs of each original pair of genes are also adjacent in the informative genome.

Key words:

Conservation of gene order operon genomic context functional inference gene neighbor method 



Research support from Wilfrid Laurier University, and as SHARCNET Chair in Biocomputing are acknowledged.


  1. 1.
    Dandekar, T., Snel, B., Huynen, M., et al. (1998) Conservation of gene order: a fingerprint of proteins that physically interact. Trends Biochem Sci 23, 324–328.PubMedCrossRefGoogle Scholar
  2. 2.
    Overbeek, R., Fonstein, M., D'Souza, M., et al. (1999) Use of contiguity on the chromosome to predict functional coupling. In Silico Biol 1, 93–108.PubMedGoogle Scholar
  3. 3.
    Overbeek, R., Fonstein, M., D'Souza, M., et al. (1999) The use of gene clusters to infer functional coupling. Proc Natl Acad Sci U S A 96, 2896–2901.PubMedCrossRefGoogle Scholar
  4. 4.
    Jacob, F., Perrin, D., Sanchez, C., et al. (1960) [Operon: a group of genes with the expression coordinated by an operator.]. C R Hebd Seances Acad Sci 250, 1727–1729.PubMedGoogle Scholar
  5. 5.
    Jacob, F., Perrin, D., Sanchez, C., et al. (2005) [The operon: a group of genes with expression coordinated by an operator.] Comptes rendus biologies 328, 514–520.PubMedCrossRefGoogle Scholar
  6. 6.
    Mushegian, A. R., Koonin, E. V. (1996) Gene order is not conserved in bacterial evolution. Trends Genet 12, 289–290.PubMedCrossRefGoogle Scholar
  7. 7.
    Bork, P. , Dandekar, T., Diaz-Lazcoz, Y., et al. (1998) Predicting function: from genes to genomes and back. J Mol Biol 283, 707–725.PubMedCrossRefGoogle Scholar
  8. 8.
    Korbel, J. O., Jensen, L. J., von Mering, C., et al. (2004) Analysis of genomic context: prediction of functional associations from conserved bidirectionally transcribed gene pairs. Nat Biotechnol 22, 911–917.PubMedCrossRefGoogle Scholar
  9. 9.
    Ermolaeva, M. D., White, O., Salzberg, S. L. (2001) Prediction of operons in microbial genomes. Nucleic Acids Res 29, 1216–1221.PubMedCrossRefGoogle Scholar
  10. 10.
    Janga, S. C., Moreno-Hagelsieb, G. (2004) Conservation of adjacency as evidence of paralogous operons. Nucleic Acids Res 32, 5392–5397.PubMedCrossRefGoogle Scholar
  11. 11.
    Snel, B., Lehmann, G., Bork, P., et al. (2000) STRING: a web-server to retrieve and display the repeatedly occurring neighbourhood of a gene. Nucleic Acids Res 28, 3442–3444.PubMedCrossRefGoogle Scholar
  12. 12.
    von Mering, C., Huynen, M., Jaeggi, D., et al. (2003) STRING: a database of predicted functional associations between proteins. Nucleic Acids Res 31, 258–261.CrossRefGoogle Scholar
  13. 13.
    Zheng, Y., Anton, B. P., Roberts, R. J., et al. (2005) Phylogenetic detection of conserved gene clusters in microbial genomes. BMC Bioinformatics 6, 243.PubMedCrossRefGoogle Scholar
  14. 14.
    Maglott, D. R., Katz, K. S., Sicotte, H., et al. (2000) NCBI's LocusLink and RefSeq. Nucleic Acids Res 28, 126–128.PubMedCrossRefGoogle Scholar
  15. 15.
    Pruitt, K. D., Tatusova, T., Maglott, D. R. (2005) NCBI Reference Sequence (Ref-Seq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res 33, D501–504.PubMedCrossRefGoogle Scholar
  16. 16.
    Altschul, S. F., Madden, T. L., Schaffer, A. A., et al. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25, 3389–3402.PubMedCrossRefGoogle Scholar
  17. 17.
    Fitch, W. M. (2000) Homology a personal view on some of the problems. Trends Genet 16, 227–231.PubMedCrossRefGoogle Scholar
  18. 18.
    Gevers, D., Vandepoele, K., Simillion, C., et al. (2004) Gene duplication and biased functional retention of paralogs in bacterial genomes. Trends Microbiol 12, 148–154.PubMedCrossRefGoogle Scholar
  19. 19.
    Schaffer, A. A., Aravind, L., Madden, T. L., et al. (2001) Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements. Nucleic Acids Res 29, 2994–3005.PubMedCrossRefGoogle Scholar
  20. 20.
    Blattner, F. R., Plunkett, G., 3rd, Bloch, C. A., et al. (1997) The complete genome sequence of Escherichia coli K-12. Science 277, 1453–1474.PubMedCrossRefGoogle Scholar
  21. 21.
    Salgado, H., Gama-Castro, S., Peralta-Gil, M., et al. (2006) RegulonDB (version 5.0): Escherichia coli K-12 transcriptional regulatory network, operon organization, and growth conditions. Nucleic Acids Res 34, D394–397.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Gabriel Moreno-Hagelsieb
    • 1
  1. 1.Department of BiologyWilfrid Laurier UniversityWaterlooCanada

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