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.

  • Technical Report
  • Published:

Comparing genomic expression patterns across species identifies shared transcriptional profile in aging

Nature Genetics volume 36, pages 197–204 (2004)Cite this article

Abstract

We developed a method for systematically comparing gene expression patterns across organisms using genome-wide comparative analysis of DNA microarray experiments. We identified analogous gene expression programs comprising shared patterns of regulation across orthologous genes. Biological features of these patterns could be identified as highly conserved subpatterns that correspond to Gene Ontology categories. Here, we demonstrate these methods by analyzing a specific biological process, aging, and show that similar analysis can be applied to a range of biological processes. We found that two highly diverged animals, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, implement a shared adult-onset expression program of genes involved in mitochondrial metabolism, DNA repair, catabolism, peptidolysis and cellular transport. Most of these changes were implemented early in adulthood. Using this approach to search databases of gene expression data, we found conserved transcriptional signatures in larval development, embryogenesis, gametogenesis and mRNA degradation.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

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

Figure 1: Comparative functional genomic analysis.
Figure 2: Correlated regulation of orthologous genes by aging in C. elegans and D. melanogaster.
Figure 3: Temporal distribution of conserved gene regulation across adulthood in C. elegans and D. melanogaster.
Figure 4: Aging, lifespan and conserved early-adult physiological change in metazoa.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. DeRisi, J.L., Iyer, V.R. & Brown, P.O. Exploring the metabolic and genetic control of gene expression on a genomic scale. Science 278, 680–686 (1997).

    Article  CAS  Google Scholar 

  2. Lipshutz, R.J., Fodor, S.P., Gingeras, T.R. & Lockhart, D.J. High density synthetic oligonucleotide arrays. Nat. Genet. 21, 20–24 (1999).

    Article  CAS  Google Scholar 

  3. Chung, C.H., Bernard, P.S. & Perou, C.M. Molecular portraits and the family tree of cancer. Nat. Genet. 32 Suppl, 533–540 (2002).

    Article  CAS  Google Scholar 

  4. Ramaswamy, S., Ross, K.N., Lander, E.S. & Golub, T.R. A molecular signature of metastasis in primary solid tumors. Nat. Genet. 33, 49–54 (2003).

    Article  CAS  Google Scholar 

  5. Hughes, T.R. et al. Functional discovery via a compendium of expression profiles. Cell 102, 109–126 (2000).

    Article  CAS  Google Scholar 

  6. Mootha, V.K. et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267–273 (2003).

    Article  CAS  Google Scholar 

  7. Wang, D.Y., Kumar, S. & Hedges, S.B. Divergence time estimates for the early history of animal phyla and the origin of plants, animals and fungi. Proc. R. Soc. Lond. B Biol. Sci. 266, 163–171 (1999).

    Article  CAS  Google Scholar 

  8. Pletcher, S.D. et al. Genome-wide transcript profiles in aging and calorically restricted Drosophila melanogaster. Curr. Biol. 12, 712–723 (2002).

    Article  CAS  Google Scholar 

  9. Hill, A.A., Hunter, C.P., Tsung, B.T., Tucker-Kellogg, G. & Brown, E.L. Genomic analysis of gene expression in C. elegans. Science 290, 809–812 (2000).

    Article  CAS  Google Scholar 

  10. Ashburner, M. et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet. 25, 25–29 (2000).

    Article  CAS  Google Scholar 

  11. Lee, C.K., Klopp, R.G., Weindruch, R. & Prolla, T.A. Gene expression profile of aging and its retardation by caloric restriction. Science 285, 1390–1393 (1999).

    Article  CAS  Google Scholar 

  12. Kayo, T., Allison, D.B., Weindruch, R. & Prolla, T.A. Influences of aging and caloric restriction on the transcriptional profile of skeletal muscle from rhesus monkeys. Proc. Natl. Acad. Sci. USA 98, 5093–5098 (2001).

    Article  CAS  Google Scholar 

  13. Lund, J. et al. Transcriptional profile of aging in C. elegans. Curr. Biol. 12, 1566–1573 (2002).

    Article  CAS  Google Scholar 

  14. Zou, S., Meadows, S., Sharp, L., Jan, L.Y. & Jan, Y.N. Genome-wide study of aging and oxidative stress response in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 97, 13726–13731 (2000).

    Article  CAS  Google Scholar 

  15. Sherlock, G. et al. The Stanford Microarray Database. Nucleic Acids Res. 29, 152–155 (2001).

    Article  CAS  Google Scholar 

  16. Finkel, T. & Holbrook, N.J. Oxidants, oxidative stress and the biology of ageing. Nature 408, 239–247 (2000).

    Article  CAS  Google Scholar 

  17. Lithgow, G.J., White, T.M., Melov, S. & Johnson, T.E. Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc. Natl. Acad. Sci. USA 92, 7540–7544 (1995).

    Article  CAS  Google Scholar 

  18. Murphy, C.T. et al. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424, 277–283 (2003).

    Article  CAS  Google Scholar 

  19. Kimura, K.D., Tissenbaum, H.A., Liu, Y. & Ruvkun, G. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277, 942–946 (1997).

    Article  CAS  Google Scholar 

  20. Kenyon, C., Chang, J., Gensch, E., Rudner, A. & Tabtiang, R.A. C. elegans mutant that lives twice as long as wild type. Nature 366, 461–464 (1993).

    Article  CAS  Google Scholar 

  21. Arbeitman, M.N. et al. Gene expression during the life cycle of Drosophila melanogaster. Science 297, 2270–2275 (2002).

    Article  CAS  Google Scholar 

  22. Jiang, M. et al. Genome-wide analysis of developmental and sex-regulated gene expression profiles in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 98, 218–223 (2001).

    Article  CAS  Google Scholar 

  23. Gaudet, J. & Mango, S.E. Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4. Science 295, 821–825 (2002).

    Article  CAS  Google Scholar 

  24. Chu, S. et al. The transcriptional program of sporulation in budding yeast. Science 282, 699–705 (1998).

    Article  CAS  Google Scholar 

  25. Reinke, V. et al. A global profile of germline gene expression in C. elegans. Mol. Cell 6, 605–616 (2000).

    Article  CAS  Google Scholar 

  26. Raghavan, A. et al. Genome-wide analysis of mRNA decay in resting and activated primary human T lymphocytes. Nucleic Acids Res. 30, 5529–5538 (2002).

    Article  CAS  Google Scholar 

  27. Wang, Y. et al. Precision and functional specificity in mRNA decay. Proc. Natl. Acad. Sci. USA 99, 5860–5865 (2002).

    Article  CAS  Google Scholar 

  28. Boldrick, J.C. et al. Stereotyped and specific gene expression programs in human innate immune responses to bacteria. Proc. Natl. Acad. Sci. USA 99, 972–977 (2002).

    Article  CAS  Google Scholar 

  29. Detweiler, C.S., Cunanan, D.B. & Falkow, S. Host microarray analysis reveals a role for the Salmonella response regulator phoP in human macrophage cell death. Proc. Natl. Acad. Sci. USA 98, 5850–5855 (2001).

    Article  CAS  Google Scholar 

  30. Guillemin, K., Salama, N.R., Tompkins, L.S. & Falkow, S. Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection. Proc. Natl. Acad. Sci. USA 99, 15136–15141 (2002).

    Article  CAS  Google Scholar 

  31. Cuadras, M.A., Feigelstock, D.A., An, S. & Greenberg, H.B. Gene expression pattern in Caco-2 cells following rotavirus infection. J. Virol. 76, 4467–4482 (2002).

    Article  CAS  Google Scholar 

  32. Whitney, A.R. et al. Individuality and variation in gene expression patterns in human blood. Proc. Natl. Acad. Sci. USA 100, 1896–1901 (2003).

    Article  CAS  Google Scholar 

  33. Dillin, A. et al. Rates of behavior and aging specified by mitochondrial function during development. Science 298, 2398–2401 (2002).

    Article  CAS  Google Scholar 

  34. Dillin, A., Crawford, D.K. & Kenyon, C. Timing requirements for insulin/IGF-1 signaling in C. elegans. Science 298, 830–834 (2002).

    Article  CAS  Google Scholar 

  35. Somani, S.M. et al. Influence of age on caloric expenditure during exercise. Int. J. Clin. Pharmacol. Ther. Toxicol. 30, 1–6 (1992).

    CAS  PubMed  Google Scholar 

  36. Bluher, M., Kahn, B. & Kahn, C. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299, 572–574 (2003).

    Article  Google Scholar 

  37. Wang, W., Cherry, J.M., Botstein, D. & Li, H. A systematic approach to reconstructing transcription networks in Saccharomycescerevisiae. Proc. Natl. Acad. Sci. USA 99, 16893–16898 (2002).

    Article  CAS  Google Scholar 

  38. Segal, E. et al. Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data. Nat. Genet. 34, 166–176 (2003).

    Article  CAS  Google Scholar 

  39. Whitfield, M.L. et al. Identification of genes periodically expressed in the human cell cycle and their expression in tumors. Mol. Biol. Cell. 13, 1977–2000 (2002).

    Article  CAS  Google Scholar 

  40. Teichmann, S.A. & Babu, M.M. Conservation of gene co-regulation in prokaryotes and eukaryotes. Trends Biotechnol. 20, 407–410 (2002).

    Article  CAS  Google Scholar 

  41. Alter, O., Brown, P.O. & Botstein, D. Generalized singular value decomposition for comparative analysis of genome-scale expression data sets of two different organisms. Proc. Natl. Acad. Sci. USA 100, 3351–3356 (2003).

    Article  CAS  Google Scholar 

  42. van Noort, V., Snel, B. & Huynen, M.A. Predicting gene function by conserved co-expression. Trends Genet. 19, 238–242 (2003).

    Article  CAS  Google Scholar 

  43. Stuart, J.M., Segal, E., Koller, D. & Kim, S.K. A gene-coexpression network for global discovery of conserved genetic modules. Science 302, 249–255 (2003).

    Article  CAS  Google Scholar 

  44. Gygi, S.P. et al. Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat. Biotechnol. 17, 994–999 (1999).

    Article  CAS  Google Scholar 

  45. Edgar, R., Domrachev, M. & Lash, A.E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30, 207–210 (2002).

    Article  CAS  Google Scholar 

  46. Brazma, A. et al. ArrayExpress—a public repository for microarray gene expression data at the EBI. Nucleic Acids Res. 31, 68–71 (2003).

    Article  CAS  Google Scholar 

  47. Stoeckert, C.J., Jr., Causton, H.C. & Ball, C.A. Microarray databases: standards and ontologies. Nat. Genet. 32 Suppl, 469–473 (2002).

    Article  CAS  Google Scholar 

  48. Rubin, G.M. et al. Comparative genomics of the eukaryotes. Science 287, 2204–2215 (2000).

    Article  CAS  Google Scholar 

  49. Hsin, H. & Kenyon, C. Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399, 362–366 (1999).

    Article  CAS  Google Scholar 

  50. Lewis, J.A. & Fleming, J.T. Basic culture methods. in Methods in Cell Biology, Volume 48: Caenorhabditis elegans: Modern Biological Analysis of an Organism (eds. Epstein, H.F. & Shakes, D.C.) 4–30 (Academic Press, San Diego, California, 1995).

    Google Scholar 

Download references

Acknowledgements

We thank A. Malmberg, C. Patil, J. DeRisi and I. Herskowitz for discussions and comments on the manuscript; A. Dillin and J. Lehrer-Graiwer for assistance in building the C. elegans microarrays; S. Meadows for assistance with D. melanogaster expression profiling; and J. DeRisi and H. Bennett for advice, instruction and use of their equipment. This work was supported by a grant from the US National Institute on Deafness and Other Communication Disorders to C.I.B., a grant from the Ellison Foundation to C.K., and a Sandler Grant, Packard Fellowship and Life Sciences Informatics grant to H.L. S.A.M. was a Howard Hughes Medical Institute graduate research fellow; C.T.M. is a Life Sciences Research postdoctoral fellow; C.I.B. and Y.N.J. are investigators of the Howard Hughes Medical Institute.

Author information

Author notes

  1. Scott D Pletcher

    Present address: Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA

Authors and Affiliations

  1. Program in Neuroscience, University of California, San Francisco, 94143, California, USA

    Steven A McCarroll, Yuh Nung Jan, Cynthia Kenyon & Cornelia I Bargmann

  2. Departments of Biochemistry and Biophysics, University of California, San Francisco, 94143, California, USA

    Coleen T Murphy, Chen-Shan Chin, Yuh Nung Jan, Cynthia Kenyon & Hao Li

  3. Department of Physiology, University of California, San Francisco, 94143, California, USA

    Sige Zou & Yuh Nung Jan

  4. Department of Biology, University College London, London, UK

    Scott D Pletcher

  5. Program in Genetics, University of California, San Francisco, 94143, California, USA

    Yuh Nung Jan, Cynthia Kenyon & Cornelia I Bargmann

  6. Program in Developmental Biology, University of California, San Francisco, 94143, California, USA

    Yuh Nung Jan, Cynthia Kenyon & Cornelia I Bargmann

  7. Howard Hughes Medical Institute, University of California, San Francisco, 94143, California, USA

    Yuh Nung Jan & Cornelia I Bargmann

  8. Department of Anatomy, University of California, San Francisco, 94143, California, USA

    Cornelia I Bargmann

  9. Program in Biophysics, University of California, San Francisco, 94143, California, USA

    Hao Li

  10. Programs in Biological and Medical Informatics, University of California, San Francisco, 94143, California, USA

    Hao Li

Authors
  1. Steven A McCarroll
    View author publications

    Search author on:PubMed Google Scholar

  2. Coleen T Murphy
    View author publications

    Search author on:PubMed Google Scholar

  3. Sige Zou
    View author publications

    Search author on:PubMed Google Scholar

  4. Scott D Pletcher
    View author publications

    Search author on:PubMed Google Scholar

  5. Chen-Shan Chin
    View author publications

    Search author on:PubMed Google Scholar

  6. Yuh Nung Jan
    View author publications

    Search author on:PubMed Google Scholar

  7. Cynthia Kenyon
    View author publications

    Search author on:PubMed Google Scholar

  8. Cornelia I Bargmann
    View author publications

    Search author on:PubMed Google Scholar

  9. Hao Li
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Hao Li.

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

McCarroll, S., Murphy, C., Zou, S. et al. Comparing genomic expression patterns across species identifies shared transcriptional profile in aging. Nat Genet 36, 197–204 (2004). https://doi.org/10.1038/ng1291

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/ng1291

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