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.

A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns

Abstract

Parallels between phylogeny and ontogeny have been discussed for almost two centuries, and a number of theories have been proposed to explain such patterns1. Especially elusive is the phylotypic stage, a phase during development where species within a phylum are particularly similar to each other2,3,4,5,6. Although this has formerly been interpreted as a recapitulation of phylogeny1, it is now thought to reflect an ontogenetic progression phase2, where strong constraints on developmental regulation and gene interactions exist2,3. Several studies have shown that genes expressed during this stage evolve at a slower rate, but it has so far not been possible to derive an unequivocal molecular signature associated with this stage7,8,9,10,11,12,13,14,15. Here we use a combination of phylostratigraphy16 and stage-specific gene expression data to generate a cumulative index that reflects the evolutionary age of the transcriptome at given ontogenetic stages. Using zebrafish ontogeny and adult development as a model, we find that the phylotypic stage does indeed express the oldest transcriptome set and that younger sets are expressed during early and late development, thus faithfully mirroring the hourglass model of morphological divergence2,3. Reproductively active animals show the youngest transcriptome, with major differences between males and females. Notably, ageing animals express increasingly older genes. Comparisons with similar data sets from flies and nematodes show that this pattern occurs across phyla. Our results indicate that an old transcriptome marks the phylotypic phase and that phylogenetic differences at other ontogenetic stages correlate with the expression of newly evolved genes.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Transcriptome age profiles for the zebrafish ontogeny.
Figure 2: Relative expression of the genes from each phylostratum across the zebrafish ontogeny (same stages as in Fig. 1) for selected phylostrata with significant differences.
Figure 3: Transcriptome age profiles for the Drosophila ontogeny, based on the data in ref. 23.
Figure 4: Comparison of differences in TAI between females and males.

Similar content being viewed by others

Accession codes

Primary accessions

Gene Expression Omnibus

Data deposits

Themicroarray data for zebrafishwere depositedat theNCBIGene Expression Omnibus (GEO) repository under the accession number GSE24616.

References

  1. Gould, S. J. Ontogeny and Phylogeny (Harvard Univ. Press, 1977)

    Google Scholar 

  2. Duboule, D. Temporal colinearity and the phylotypic progression: a basis for the stability of a vertebrate Bauplan and the evolution of morphologies through heterochrony. Dev. Suppl. 135–142(1994)

  3. Raff, R. A. The Shape of Life: Genes Development, and the Evolution of Animal Form (Univ. Chicago Press, 1996)

    Google Scholar 

  4. Richardson, M. K. et al. There is no highly conserved embryonic stage in the vertebrates: implications for current theories of evolution and development. Anat. Embryol. (Berl.) 196, 91–106 (1997)

    CAS  Google Scholar 

  5. Hall, B. K. Phylotypic stage or phantom: is there a highly conserved embryonic stage in vertebrates? Trends Ecol. Evol. 12, 461–463 (1997)

    CAS  Google Scholar 

  6. Bininda-Emonds, O. R., Jeffery, J. E. & Richardson, M. K. Inverting the hourglass: quantitative evidence against the phylotypic stage in vertebrate development. Proc. R. Soc. Lond. B 270, 341–346 (2003)

    Google Scholar 

  7. Hanada, K., Shiu, S. H. & Li, W. H. The Nonsynonymous/synonymous substitution rate ratio versus the radical/conservative replacement rate ratio in the evolution of mammalian genes. Mol. Biol. Evol. 24, 2235–2241 (2007)

    CAS  Google Scholar 

  8. Comte, A., Roux, J. & Robinson-Rechavi, M. Molecular signaling in zebrafish development and the vertebrate phylotypic period. Evol. Dev. 12, 144–156 (2010)

    CAS  Google Scholar 

  9. Yassin, A., Lienau, E. K., Narechania, A. & DeSalle, R. Catching the phylogenic history through the ontogenic hourglass: a phylogenomic analysis of Drosophila body segmentation genes. Evol. Dev. 12, 288–295 (2010)

    Google Scholar 

  10. Davis, J. C., Brandman, O. & Petrov, D. A. Protein evolution in the context of Drosophila development. J. Mol. Evol. 60, 774–785 (2005)

    CAS  Google Scholar 

  11. Hazkani-Covo, E., Wool, D. & Graur, D. In search of the vertebrate phylotypic stage: a molecular examination of the developmental hourglass model and von Baer's third law. J. Exp. Zoolog. B 304, 150–158 (2005)

    Google Scholar 

  12. Irie, N. & Sehara-Fujisawa, A. The vertebrate phylotypic stage and an early bilaterian-related stage in mouse embryogenesis defined by genomic information. BMC Biol. 5, 1 (2007)

    Google Scholar 

  13. Roux, J. & Robinson-Rechavi, M. Developmental constraints on vertebrate genome evolution. PLoS Genet. 4, e1000311 (2008)

    Google Scholar 

  14. Cruickshank, T. & Wade, M. J. Microevolutionary support for a developmental hourglass: gene expression patterns shape sequence variation and divergence in Drosophila . Evol. Dev. 10, 583–590 (2008)

    Google Scholar 

  15. Artieri, C. G., Haerty, W. & Singh, R. S. Ontogeny and phylogeny: molecular signatures of selection, constraint, and temporal pleiotropy in the development of Drosophila . BMC Biol. 7, 42 (2009)

    Google Scholar 

  16. Domazet-Lošo, T., Brajković, J. & Tautz, D. A phylostratigraphy approach to uncover the genomic history of major adaptations in metazoan lineages. Trends Genet. 23, 533–539 (2007)

    Google Scholar 

  17. Domazet-Lošo, T. & Tautz, D. An ancient evolutionary origin of genes associated with human genetic diseases. Mol. Biol. Evol. 25, 2699–2707 (2008)

    Google Scholar 

  18. Domazet-Lošo, T. & Tautz, D. Phylostratigraphic tracking of cancer genes suggests a link to the emergence of multicellularity in metazoa. BMC Biol. 8, 66 (2010)

    Google Scholar 

  19. Parichy, D. M., Elizondo, M. R., Mills, M. G., Gordon, T. N. & Engeszer, R. E. Normal table of postembryonic zebrafish development: staging by externally visible anatomy of the living fish. Dev. Dyn. 238, 2975–3015 (2009)

    Google Scholar 

  20. Grandel, H. & Schulte-Merker, S. The development of the paired fins in the zebrafish (Danio rerio). Mech. Dev. 79, 99–120 (1998)

    CAS  Google Scholar 

  21. Leys, S. P. & Eerkes-Medrano, D. Gastrulation in calcareous sponges: In search of Haeckel’s Gastraea. Integr. Comp. Biol. 45, 342–351 (2005)

    Google Scholar 

  22. Flatt, T., Moroz, L. L., Tatar, M. & Heyland, A. Comparing thyroid and insect hormone signaling. Integr. Comp. Biol. 46, 777–794 (2006)

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  24. Sander, K. In Development and Evolution: the sixth Symposium of the British Society for Developmental Biology (eds Goodwin, B. C., Holder, N. & Wylie, C. C.) 137–159 (Cambridge Univ. Press, 1983)

    Google Scholar 

  25. 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)

    CAS  Google Scholar 

  26. Koutsos, A. C. et al. Life cycle transcriptome of the malaria mosquito Anopheles gambiae and comparison with the fruitfly Drosophila melanogaster . Proc. Natl Acad. Sci. USA 104, 11304–11309 (2007)

    CAS  Google Scholar 

  27. Domazet-Lošo, T. & Tautz, D. An evolutionary analysis of orphan genes in Drosophila . Genome Res. 13, 2213–2219 (2003)

    Google Scholar 

  28. Khalturin, K., Hemmrich, G., Fraune, S., Augustin, R. & Bosch, T. C. More than just orphans: are taxonomically-restricted genes important in evolution? Trends Genet. 25, 404–413 (2009)

    CAS  Google Scholar 

  29. Nolte, A. W., Renaut, S. & Bernatchez, L. Divergence in gene regulation at young life history stages of whitefish (Coregonus sp.) and the emergence of genomic isolation. BMC Evol. Biol. 9, 59 (2009)

    Google Scholar 

  30. Levine, M. T., Jones, C. D., Kern, A. D., Lindfors, H. A. & Begun, D. J. Novel genes derived from noncoding DNA in Drosophila melanogaster are frequently X-linked and show testis-biased expression. Proc. Natl Acad. Sci. USA 103, 9935–9939 (2006)

    CAS  Google Scholar 

  31. Kimmel, C. B., Ballard, W. W., Kimmel, S. R., Ullmann, B. & Schilling, T. F. Stages of embryonic development of the zebrafish. Dev. Dyn. 203, 253–310 (1995)

    CAS  Google Scholar 

  32. Efron, B. & Tibshirani, R. Bootstrap methods for standard errors, confidence intervals, and other measures of statistical accuracy. Stat. Sci. 1, 54–75 (1986)

    Google Scholar 

Download references

Acknowledgements

We thank B. Walderich for providing zebrafish, A. Nolte, E. Blohm-Sievers, B. Kleinhenz, L. Turner and J. Bryk for laboratory support, R. Bakarić has provided the phylostratigraphic map of C. elegans, and M. Domazet-Lošo and V. Dunjko have helped with statistics. L. Boell, F. Chang and A. Pozhitkov have made suggestions on the manuscript. This work was supported by Unity Through Knowledge Fund (grant No. 49), Adris Foundation and funds of the Max-Planck Society. Computational resources were provided by CSTMB and RBI (Phylostrat Cluster).

Author information

Authors and Affiliations

Authors

Contributions

T.D.-L. conceived the basic idea and conducted the experiments; D.T. contributed to the evaluation and interpretation of the results. Both authors wrote the manuscript.

Corresponding author

Correspondence to Tomislav Domazet-Lošo.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Notes 1- 2, additional references and Supplementary Figures 1- 4 with legends. (PDF 1998 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Domazet-Lošo, T., Tautz, D. A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns. Nature 468, 815–818 (2010). https://doi.org/10.1038/nature09632

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature09632

This article is cited by

Comments

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.

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