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.

  • Opinion
  • Published:

The molecular elements that underlie developmental evolution

Abstract

Abundant evidence indicates that developmental evolution, the foundation of morphological evolution, is based on changes in gene function. Over the past decade a consensus has developed that transcriptional regulation, acting through enhancer sequences, is the primary level of evolutionarily significant change. Here we propose that other regulatory levels are probably as important as enhancers in developmental evolution. We also explain why these alternative regulatory levels might have been neglected, and briefly discuss ways to test our hypothesis.

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: Hypotheses for the evolution of regulatory mutations at ARLs.

Similar content being viewed by others

References

  1. King, M. C. & Wilson, A. C. Evolution at two levels in humans and chimpanzees. Science 188, 107–116 (1975).

    Article  CAS  PubMed  Google Scholar 

  2. Britten, R. J. & Davidson, E. H. Repetitive and non-repetitive DNA sequences and a speculation on the origins of evolutionary novelty. Q. Rev. Biol. 46, 111–138 (1971).

    Article  CAS  PubMed  Google Scholar 

  3. Mann, R. S. & Carroll, S. B. Molecular mechanisms of selector gene function and evolution. Curr. Opin. Genet. Dev. 12, 592–600 (2002).

    Article  CAS  PubMed  Google Scholar 

  4. Simpson, P. Evolution of development in closely related species of flies and worms. Nature Rev. Genet. 3, 907–917 (2002).

    Article  CAS  PubMed  Google Scholar 

  5. Levine, M. & Tjian, R. Transcription regulation and animal diversity. Nature 424, 147–151 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Wray, G. A. Transcriptional regulation and the evolution of development. Int. J. Dev. Biol. 47, 675–684 (2003).

    CAS  PubMed  Google Scholar 

  7. Davidson, E. H. Genomic regulatory systems (Academic Press, San Diego, California, 2001).

    Google Scholar 

  8. Carroll, S. B. Homeotic genes and the evolution of arthropods and chordates. Nature 376, 479–485 (1995).

    Article  CAS  PubMed  Google Scholar 

  9. Akam, M. Hox genes, homeosis and the evolution of segment identity: no need for hopeless monsters. Int. J. Dev. Biol. 42, 445–451 (1998).

    CAS  PubMed  Google Scholar 

  10. Stern, D. L. Evolutionary developmental biology and the problem of variation. Evolution 54, 1079–1091 (2000).

    Article  CAS  PubMed  Google Scholar 

  11. Ludwig, M. Z., Patel, N. H. & Kreitman, M. Functional analysis of eve stripe 2 enhancer evolution in Drosophila: rules governing conservation and change. Development 125, 949–958 (1998).

    CAS  PubMed  Google Scholar 

  12. Wray, G. A. et al. The evolution of transcriptional regulation in eukaryotes. Mol. Biol. Evol. 20, 1377–1419 (2003).

    Article  CAS  PubMed  Google Scholar 

  13. Rockman, M. V. & Wray, G. A. Abundant raw material for cis-regulatory evolution in humans. Mol. Biol. Evol. 19, 1991–2004 (2002).

    Article  CAS  PubMed  Google Scholar 

  14. Crick, F. H. On protein synthesis. Symp. Soc. Exp. Biol. 12, 138–163 (1958).

    CAS  PubMed  Google Scholar 

  15. Simeone, A. et al. A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo. EMBO J. 12, 2735–2747 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Simeone, A. Otx1 and Otx2 in the development and evolution of the mammalian brain. EMBO J. 17, 6790–6798 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Boyl, P. P. et al. Forebrain and midbrain development requires epiblast-restricted Otx2 translational control mediated by its 3′ UTR. Development 128, 2989–3000 (2001).

    CAS  PubMed  Google Scholar 

  18. Acampora, D. et al. Otx genes in evolution: are they involved in instructing the vertebrate brain morphology? J. Anat. 199, 53–62 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kuersten, S. & Goodwin, E. B. The power of the 3′ UTR: translational control and development. Nature Rev. Genet. 4, 626–637 (2003).

    Article  CAS  PubMed  Google Scholar 

  20. Palacios, I. M. & St Johnston, D. Getting the message across: the intracellular localization of mRNAs in higher eukaryotes. Annu. Rev. Cell Dev. Biol. 17, 569–614 (2001).

    Article  CAS  PubMed  Google Scholar 

  21. Zaidi, S. H. & Malter, J. S. Nucleolin and heterogeneous nuclear ribonucleoprotein C proteins specifically interact with the 3′-untranslated region of amyloid protein precursor mRNA. J. Biol. Chem. 270, 17292–17298 (1995).

    Article  CAS  PubMed  Google Scholar 

  22. Maniatis, T. & Tasic, B. Alternative pre-mRNA splicing and proteome expansion in metazoans. Nature 418, 236–243 (2002).

    Article  CAS  PubMed  Google Scholar 

  23. Black, D. L. Protein diversity from alternative splicing: a challenge for bioinformatics and post-genome biology. Cell 103, 367–370 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Graveley, B. R. Alternative splicing: increasing diversity in the proteomic world. Trends Genet. 17, 100–107 (2001).

    Article  CAS  PubMed  Google Scholar 

  25. Garcia-Blanco, M. A., Baraniak, A. P. & Lasda, E. L. Alternative splicing in disease and therapy. Nature Biotechnol. 22, 535–546 (2004).

    Article  CAS  Google Scholar 

  26. Mine, M. et al. Splicing error in E1α pyruvate dehydrogenase mRNA caused by novel intronic mutation responsible for lactic acidosis and mental retardation. J. Biol. Chem. 278, 11768–11772 (2003).

    Article  CAS  PubMed  Google Scholar 

  27. Hutton, M. et al. Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393, 702–705 (1998).

    Article  CAS  PubMed  Google Scholar 

  28. Varani, L. et al. Structure of tau exon 10 splicing regulatory element RNA and destabilization by mutations of frontotemporal dementia and parkinsonism linked to chromosome 17. Proc. Natl Acad. Sci. USA 96, 8229–8234 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Jiang, Z., Cote, J., Kwon, J. M., Goate, A. M. & Wu, J. Y. Aberrant splicing of tau pre-mRNA caused by intronic mutations associated with the inherited dementia frontotemporal dementia with parkinsonism linked to chromosome 17. Mol. Cell. Biol. 20, 4036–4048 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Schutt, C. & Nothiger, R. Structure, function and evolution of sex-determining systems in Dipteran insects. Development. 127, 667–677 (2000).

    CAS  PubMed  Google Scholar 

  31. Soller, M. & White, K. ELAV inhibits 3′-end processing to promote neural splicing of ewg pre-mRNA. Genes Dev. 17, 2526–2538 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Brennecke, J., Hipfner, D. R., Stark, A., Russell, R. B. & Cohen, S. M. bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113, 25–36 (2003).

    Article  CAS  PubMed  Google Scholar 

  33. Mansfield, J. H. et al. MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nature Genet. 36, 1079–1083 (2004).

    Article  CAS  PubMed  Google Scholar 

  34. Hsieh, J. J., Cheng, E. H. & Korsmeyer, S. J. Taspase1: a threonine aspartase required for cleavage of MLL and proper HOX gene expression. Cell 115, 293–303 (2003).

    Article  CAS  PubMed  Google Scholar 

  35. Chambeyron, S. & Bickmore, W. A. Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription. Genes Dev. 18, 1119–1130 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Schadt, E. E. et al. Genetics of gene expression surveyed in maize, mouse and man. Nature 422, 297–302 (2003).

    Article  CAS  PubMed  Google Scholar 

  37. Wittkopp, P. J., Haerum, B. K. & Clark, A. G. Evolutionary changes in cis and trans gene regulation. Nature 430, 85–88 (2004).

    Article  CAS  PubMed  Google Scholar 

  38. Yvert, G. et al. Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors. Nature Genet. 35, 57–64 (2003).

    Article  CAS  PubMed  Google Scholar 

  39. Krawczak, M., Reiss, J. & Cooper, D. N. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum. Genet. 90, 41–54 (1992).

    Article  CAS  PubMed  Google Scholar 

  40. Caceres, J. F. & Kornblihtt, A. R. Alternative splicing: multiple control mechanisms and involvement in human disease. Trends Genet. 18, 186–193 (2002).

    Article  CAS  PubMed  Google Scholar 

  41. Pagani, F. & Baralle, F. E. Genomic variants in exons and introns: identifying the splicing spoilers. Nature Rev. Genet. 5, 389–396 (2004).

    Article  CAS  PubMed  Google Scholar 

  42. Jacob, F. & Monod, J. Genetic regulatory mechanisms in the synthesis of proteins. J. Mol. Biol. 3, 318–356 (1961).

    Article  CAS  PubMed  Google Scholar 

  43. Denny, P. C. & Tyler, A. Activation of protein biosynthesis in non-nucleate fragments of sea urchin eggs. Biochem. Biophys. Res. Commun. 14, 245–249 (1964).

    Article  CAS  PubMed  Google Scholar 

  44. Gross, P. R. & Cousineau, G. H. Effects of actinomycin D on macromolecule synthesis and early development in sea urchin eggs. Biochem. Biophys. Res. Commun. 10, 321–326 (1963).

    Article  CAS  PubMed  Google Scholar 

  45. Gross, P. R. & Cousineau, G. H. Macromolecule synthesis and the influence of actinomycin on early development. Exp. Cell Res. 33, 368–395 (1964).

    Article  CAS  PubMed  Google Scholar 

  46. Brachet, J. & Denis, H. Effects of actinomycin D on morphogenesis. Nature 198, 205–206 (1963).

    Article  CAS  PubMed  Google Scholar 

  47. Rifkin, S. A., Kim, J. & White, K. P. Evolution of gene expression in the Drosophila melanogaster subgroup. Nature Genet. 33, 138–144 (2003).

    Article  CAS  PubMed  Google Scholar 

  48. Khaitovich, P. et al. Regional patterns of gene expression in human and chimpanzee brains. Genome Res. 14, 1462–1473 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Prasad, J., Colwill, K., Pawson, T. & Manley, J. L. The protein kinase Clk/Sty directly modulates SR protein activity: both hyper- and hypophosphorylation inhibit splicing. Mol. Cell. Biol. 19, 6991–7000 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kadonaga, J. T. The DPE, a core promoter element for transcription by RNA polymerase II. Exp. Mol. Med. 34, 259–264 (2002).

    Article  CAS  PubMed  Google Scholar 

  51. Misra, S. et al. Annotation of the Drosophila melanogaster euchromatic genome: a systematic review. Genome Biol. 3, RESEARCH0083 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Fairbrother, W. G., Yeh, R. F., Sharp, P. A. & Burge, C. B. Predictive identification of exonic splicing enhancers in human genes. Science 297, 1007–1013 (2002).

    Article  CAS  PubMed  Google Scholar 

  53. Fairbrother, W. G. et al. RESCUE-ESE identifies candidate exonic splicing enhancers in vertebrate exons. Nucleic Acids Res. 32, W187–W190 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Brem, R. B., Yvert, G., Clinton, R. & Kruglyak, L. Genetic dissection of transcriptional regulation in budding yeast. Science 296, 752–755 (2002).

    Article  CAS  PubMed  Google Scholar 

  55. Morley, M. et al. Genetic analysis of genome-wide variation in human gene expression. Nature 430, 743–747 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

C.R.A. wishes to thank The Wellcome Trust for support, and members of the Laboratory for Development and Evolution for helpful comments and discussions on the ideas in this manuscript. The authors wish to thank the comments of two anonymous referees, which have contributed to improving the quality of this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Claudio R. Alonso.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

Entrez

ban

CFTR

Hoxb8

MAPT

Otx2

PDHA1

OMIM

cystic fibrosis

FURTHER INFORMATION

Claudio Alonso's web page

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alonso, C., Wilkins, A. The molecular elements that underlie developmental evolution. Nat Rev Genet 6, 709–715 (2005). https://doi.org/10.1038/nrg1676

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg1676

This article is cited by

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