Comparative Genomics

Digging for Data
  • Matthew B. Avison
Part of the Methods in Molecular Biology™ book series (MIMB, volume 266)


Comparative genomics is a science in its infancy. It has been driven by a huge increase in freely available genome-sequence data, and the development of computer techniques to allow whole-genome sequence analyses. Other approaches, which use hybridization as a method for comparing the gene content of related organisms, are rising alongside these more bioinformatic methods. All these approaches have been pioneered using bacterial genomes because of their simplicity and the large number of complete genome sequences available. The aim of bacterial comparative genomics is to determine what genotypic differences are important for the expression of particular traits (e.g., antibiotic resistance, virulence, or host preference). The benefits of such studies will be a deeper understanding of these phenomena; the possibility of exposing novel drug targets, including those for antivirulence drugs; and the development of molecular techniques that reveal patients who are infected with virulent organisms so that health care resources can be allocated appropriately. With more and more genome sequences becoming available, the rise of comparative genomics continues apace.

Key Words

Comparative genomics genome sequence microarrays proteomics BLAST genomic island synteny horizontal gene transfer mutation hybridization bacteriology 


  1. 1.
    Blattner, F. R., Plunkett, G., 3rd, Bloch, C. A., Perna, N. T., Burland, V., Riley, M., et al. (1997) The complete genome sequence of Escherichia coli K-12. Science 277, 1453–1474.PubMedCrossRefGoogle Scholar
  2. 2.
    Perna, N. T., Plunkett, G., 3rd, Burland, V., Mau, B., Glasner, J. D., Rose, D. J., et al. (2001) Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 409, 529–533.PubMedCrossRefGoogle Scholar
  3. 3.
    Reid, S. D., Herbelin, C. J., Bumbaugh, A. C., Selander, R. K., and Whittam, T. S. (2000) Parallel evolution of virulence in pathogenic Escherichia coli. Nature 406, 64–67.PubMedCrossRefGoogle Scholar
  4. 4.
    Stover, C. K., Pham, X. Q., Erwin, A. L., Mizoguchi, S. D., Warrener, P., Hickey, M. J., et al. (2000) Complete genome sequence of Pseudomonas aeruginosa PA01, an opportunistic pathogen. Nature 406, 959–964.PubMedCrossRefGoogle Scholar
  5. 5.
    Clarke, G. D., Beiko, R. G., Ragan, M. A., and Charlebois, R. L. (2002) Inferring genome trees by using a filter to eliminate phylogenetically discordant sequences and a distance matrix based on mean normalized BLASTP scores. J. Bacteriol. 184, 2072–2080.PubMedCrossRefGoogle Scholar
  6. 6.
    Edwards, R. A., Olsen, G. J., and Maloy, S. R. (2002) Comparative genomics of closely related salmonellae. Trends Microbiol. 10, 94–99.PubMedCrossRefGoogle Scholar
  7. 7.
    Parkhill, J., Dougan, G., James, K. D., Thomson, N. R., Pickard, D., Wain, J., et al. (2001) Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18. Nature 413, 848–852.PubMedCrossRefGoogle Scholar
  8. 8.
    McClelland, M., Sanderson, K. E., Spieth, J., Clifton, S. W., Latreille, P., Courtney, L., et al. (2001) Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413, 852–856.PubMedCrossRefGoogle Scholar
  9. 9.
    Hansen-Wester, I. and Hensel, M. (2002) Genome-based identification of chromosomal regions specific for Salmonella spp. Infect. Immun. 70, 2351–2360.PubMedCrossRefGoogle Scholar
  10. 10.
    Hou, Y. M. (1999) Transfer RNAs and pathogenicity islands. Trends Biochem. Sci. 24, 295–298.PubMedCrossRefGoogle Scholar
  11. 11.
    Parkhill, J., Wren, B. W., Thomson, N. R., Titball, R. W., Holden, M. T., Prentice, M. B., et al. (2001) Genome sequence of Yersinia pestis, the causative agent of plague. Nature 413, 523–527.PubMedCrossRefGoogle Scholar
  12. 12.
    Deng, W., Burland, V., Plunkett, G., 3rd, Boutin, A., Mayhew, G. F., Liss, P., et al. (2002) Genome sequence of Yersinia pestis KIM. J. Bacteriol. 184, 4601–4611.PubMedCrossRefGoogle Scholar
  13. 13.
    Kuroda, M., Ohta, T., Uchiyama, I., Baba, T., Yuzawa, H., Kobayashi, I., et al. (2001) Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Lancet 357, 1225–1240.PubMedCrossRefGoogle Scholar
  14. 14.
    Avison, M. B., Bennett, P. M., Howe, R. A., and Walsh, T. R. (2002) Preliminary analysis of the genetic basis for vancomycin resistance in Staphylococcus aureus strain Mu50. J. Antimicrob. Chemother. 49, 255–260.PubMedCrossRefGoogle Scholar
  15. 15.
    O’Neill, A. J. and Chopra, I. (2002) Insertional inactivation of mutS in Staphylococcus aureus reveals potential for elevated mutation frequencies, although the prevalence of mutators in clinical isolates is low. J. Antimicrob. Chemother. 50, 161–169.PubMedCrossRefGoogle Scholar
  16. 16.
    Baba, T., Takeuchi, F., Kuroda, M., Yuzawa, H., Aoki, K., Oguchi, A., et al. (2002) Genome and virulence determinants of high virulence community-acquired MRSA. Lancet 359, 1819–1827.PubMedCrossRefGoogle Scholar
  17. 17.
    Herron, L. L., Chakravarty, R., Dwan, C., Fitzgerald, J. R., Musser, J. M., Retzel, E., et al. (2002) Genome sequence survey identifies unique sequences and key virulence genes with unusual rates of amino acid substitution in bovine Staphylococcus aureus. Infect. Immun. 70, 3978–3981.PubMedCrossRefGoogle Scholar
  18. 18.
    Cunningham, M. W. (2000) Pathogenesis of group A streptococcal infections. Clin. Microbiol. Rev. 13, 470–511.PubMedCrossRefGoogle Scholar
  19. 19.
    Smoot, J. C., Barbian, K. D., Van Gompel, J. J., Smoot, L. M., Chaussee, M. S., Sylva, G. L., et al. (2002) Genome sequence and comparative microarray analysis of serotype M18 group A Streptococcus strains associated with acute rheumatic fever outbreaks. Proc. Natl. Acad. Sci. USA 99, 4668–4673.PubMedCrossRefGoogle Scholar
  20. 20.
    Ferretti, J. J., McShan, W. M., Ajdic, D., Savic, D. J., Savic, G., Lyon, K., et al. (2001) Complete genome sequence of an M1 strain of Streptococcus pyogenes. Proc. Natl. Acad. Sci. USA 98, 4658–4663.PubMedCrossRefGoogle Scholar
  21. 21.
    Cole, S. T., Brosch, R., Parkhill, J., Garnier, T., Churcher, C., Harris, D., et al. (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537–544.PubMedCrossRefGoogle Scholar
  22. 22.
    Cole, S. T. (2002) Comparative and functional genomics of the Mycobacterium tuberculosis complex. Microbiology 148, 2919–2928.PubMedGoogle Scholar
  23. 23.
    Cole, S. T., Eiglmeier, K., Parkhill, J., James, K. D., Thomson, N. R., Wheeler, P. R., et al. (2001) Massive gene decay in the leprosy bacillus. Nature 409, 1007–1011.PubMedCrossRefGoogle Scholar
  24. 24.
    Janssen, P. J., Audit, B., and Ouzounis, C. A. (2001) Strain-specific genes of Helicobacter pylori: distribution, function and dynamics. Nucleic Acids Res. 29, 4395–4404.PubMedCrossRefGoogle Scholar
  25. 25.
    Garcia-Vallve, S., Janssen, P. J., and Ouzounis, C. A. (2002) Genetic variation between Helicobacter pylori strains: gene acquisition or loss? Trends Microbiol. 10, 445–447.PubMedCrossRefGoogle Scholar
  26. 26.
    Thompson, L. J. and de Reuse, H. (2002) Genomics of Helicobacter pylori. Helicobacter 7, 1–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Ochman, H. and Jones, I. B. (2000) Evolutionary dynamics of full genome content in Escherichia coli. EMBO J. 19, 6637–6643.PubMedCrossRefGoogle Scholar
  28. 28.
    Richmond, C. S., Glasner, J. D., Mau, R., Jin, H., and Blattner, F. R. (1999) Genome-wide expression profiling in Escherichia coli K-12. Nucleic Acids Res. 27, 3821–3835.PubMedCrossRefGoogle Scholar
  29. 29.
    Dziejman, M., Balon, E., Boyd, D., Fraser, C. M., Heidelberg, J. F., and Mekalanos, J. J. (2002) Comparative genomic analysis of Vibrio cholerae: genes that correlate with cholera endemic and pandemic disease. Proc. Natl. Acad. Sci. USA 99, 1556–1561.PubMedCrossRefGoogle Scholar
  30. 30.
    Heidelberg, J. F., Eisen, J. A., Nelson, W. C., Clayton, R. A., Gwinn, M. L., Dodson, R. J., et al. (2000) DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature 406, 477–483.PubMedCrossRefGoogle Scholar
  31. 31.
    Behr, M. A., Wilson, M. A., Gill, W. P., Salamon, H., Schoolnik, G. K., Rane, S., et al. (1999) Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science 284, 1520–1523.PubMedCrossRefGoogle Scholar
  32. 32.
    Malloff, C. A., Fernandez, R. C., and Lam, W. L. (2001) Bacterial comparative genomic hybridization: a method for directly identifying lateral gene transfer. J. Mol. Biol. 312, 1–5.PubMedCrossRefGoogle Scholar
  33. 33.
    Brown, P. K. and Curtiss, R., 3rd (1996) Unique chromosomal regions associated with virulence of an avian pathogenic Escherichia coli strain. Proc. Natl. Acad. Sci. USA 93, 11,149–11,154.PubMedCrossRefGoogle Scholar
  34. 34.
    Pradel, N., Leroy-Setrin, S., Joly, B., and Livrelli, V. (2002) Genomic subtraction to identify and characterize sequences of Shiga toxin-producing Escherichia coli O91:H21. Appl. Environ. Microbiol. 68, 2316–2325.PubMedCrossRefGoogle Scholar
  35. 35.
    Ahmed, I. H., Manning, G., Wassenaar, T. M., Cawthraw, S., and Newell, D. G. (2002) Identification of genetic differences between two Campylobacter jejuni strains with different colonization potentials. Microbiology 148, 1203–1212.PubMedGoogle Scholar
  36. 36.
    Bahrani-Mougeot, F. K., Pancholi, S., Daoust, M., and Donnenberg, M. S. (2001) Identification of putative urovirulence genes by subtractive cloning. J. Infect. Dis. 183(Suppl 1), S21–S23.PubMedCrossRefGoogle Scholar
  37. 37.
    Zhang, L., Foxman, B., Manning, S. D., Tallman, P., and Marrs, C. F. (2000) Molecular epidemiologic approaches to urinary tract infection gene discovery in uropathogenic Escherichia coli. Infect. Immun. 68, 2009–2015.PubMedCrossRefGoogle Scholar
  38. 38.
    Jungblut, P. R. (2001) Proteome analysis of bacterial pathogens. Microbes Infect. 3, 831–840.PubMedCrossRefGoogle Scholar
  39. 39.
    Betts, J. C., Dodson, P., Quan, S., Lewis, A. P., Thomas, P. J., Duncan, K. et al. (2000) Comparison of the proteome of Mycobacterium tuberculosis strain H37Rv with clinical isolate CDC 1551. Microbiology 146, 3205–3216.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2004

Authors and Affiliations

  • Matthew B. Avison
    • 1
  1. 1.Department of BiochemistryUniversity of Bristol, School of Medical SciencesBristolUK

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