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.

Developmental constraints shape the evolution of the nematode mid-developmental transition

Abstract

Evolutionary theory assumes that genetic variation is uniform and gradual in nature, yet morphological and gene expression studies have revealed that different life-stages exhibit distinct levels of cross-species conservation. In particular, a stage in mid-embryogenesis is highly conserved across species of the same phylum, suggesting that this stage is subject to developmental constraints, either by increased purifying selection or by a strong mutational bias. An alternative explanation, however, holds that the same ‘hourglass’ pattern of variation may result from increased positive selection at the earlier and later stages of development. To distinguish between these scenarios, we examined gene expression variation in a population of the nematode Caenorhabditis elegans using an experimental design that eliminated the influence of positive selection. By measuring gene expression for all genes throughout development in 20 strains, we found that variations were highly uneven throughout development, with a significant depletion during mid-embryogenesis. In particular, the family of homeodomain transcription factors, whose expression generally coincides with mid-embryogenesis, evolved under high constraint. Our data further show that genes responsible for the integration of germ layers during morphogenesis are the most constrained class of genes. Together, these results provide strong evidence for developmental constraints as the mechanism underlying the hourglass model of animal evolution. Understanding the pattern and mechanism of developmental constraints provides a framework to understand how evolutionary processes have interacted with embryogenesis and led to the diversity of animal life on Earth.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Studying developmental constraints on temporal gene expression during development.
Figure 2: Mid-embryogenesis is highly conserved in MA strains.
Figure 3: Analysis of functional gene groups shows that homeodomain genes are highly conserved across MA strains.
Figure 4: The phylotypic stage is a conserved period of integration between the endoderm and ectoderm.

References

  1. Arthur, W. Evolution: A Developmental Approach (Wiley, 2010).

  2. Gerhart, J. & Kirschner, M. Cells, Embryos and Evolution (Wiley, 1997).

    Google Scholar 

  3. Carroll, S. B., Grenier, J. K. & Weatherbee, S. D. From DNA to Diversity: Molecular Genetics and the Evolution of Animal Design (Wiley, 2004).

    Google Scholar 

  4. Davidson, E. H. & Erwin, D. H. Gene regulatory networks and the evolution of animal body plans. Science 311, 796–800 (2006).

    CAS  Article  Google Scholar 

  5. Wallace, A. R. Contributions to the Theory of Natural Selection. A Series of Essays (Macmillan, 1870).

    Google Scholar 

  6. Mayr, E. Animal Species and Evolution (Belknap/Harvard Univ. Press, 1963).

    Book  Google Scholar 

  7. Arthur, W. The interaction between developmental bias and natural selection: from centipede segments to a general hypothesis. Heredity 89, 239–246 (2002).

    CAS  Article  Google Scholar 

  8. Hall, B. K. Evolutionary Developmental Biology (Springer Science & Business Media, 1998).

    Google Scholar 

  9. Smith, J. M. et al. Developmental constraints and evolution: a perspective from the Mountain Lake Conference on Development and Evolution. Q. Rev. Biol. 60, 265–287 (1985).

    Article  Google Scholar 

  10. von Baer, K. E. Über Entwickelungsgeschichte der Thiere. Beobachtung und Reflexion (Bornträger, 1828).

    Book  Google Scholar 

  11. Haeckel, E. H. P. A. Anthropogenie; oder, Entwickelungsgeschichte des Menschen... Keimes- und Stammes-geschichte (Leipzig, 1874).

    Google Scholar 

  12. Sander, K. Pattern specification in the insect embryo. Ciba Foundation Symposium 29: Cell Patterning (eds Porter, R. & Rivers, J. ) 241–263 (Wiley, 1975).

    Google Scholar 

  13. Goldstein, B., Frisse, L. M. & Thomas, W. K. Embryonic axis specification in nematodes: evolution of the first step in development. Curr. Biol. 8, 157–160 (1998).

    CAS  Article  Google Scholar 

  14. Irmler, I., Schmidt, K. & Starck, J. M. Developmental variability during early embryonic development of zebra fish, Danio rerio. J. Exp. Zool. B 302, 446–457 (2004).

    Google Scholar 

  15. 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).

  16. Slack, J. M., Holland, P. W. & Graham, C. F. The zootype and the phylotypic stage. Nature 361, 490–492 (1993).

    CAS  Article  Google Scholar 

  17. Raff, R. A. The Shape of Life: Genes, Development, and the Evolution of Animal Form (Univ. Chicago Press, 2012).

    Google Scholar 

  18. Kalinka, A. T. et al. Gene expression divergence recapitulates the developmental hourglass model. Nature 468, 811–814 (2010).

    CAS  Article  Google Scholar 

  19. Levin, M., Hashimshony, T., Wagner, F. & Yanai, I. Developmental milestones punctuate gene expression in the Caenorhabditis embryo. Dev. Cell 22, 1101–1108 (2012).

    CAS  Article  Google Scholar 

  20. 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. Zool. B 304, 150–158 (2005).

    Article  Google Scholar 

  21. Irie, N. & Kuratani, S. Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis. Nat. Commun. 2, 248 (2011).

    Article  Google Scholar 

  22. Domazet-Lošo, T. & Tautz, D. A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns. Nature 468, 815–818 (2010).

    Article  Google Scholar 

  23. Quint, M. et al. A transcriptomic hourglass in plant embryogenesis. Nature 490, 98–101 (2012).

    CAS  Article  Google Scholar 

  24. Drost, H. -G., Gabel, A., Grosse, I. & Quint, M. Evidence for active maintenance of phylotranscriptomic hourglass patterns in animal and plant embryogenesis. Mol. Biol. Evol. 32, 1221–1231 (2015).

    CAS  Article  Google Scholar 

  25. Cheng, X., Hui, J. H. L., Lee, Y. Y., Wan Law, P. T. & Kwan, H. S. A ‘developmental hourglass’ in fungi. Mol. Biol. Evol. 32, 1556–1566 (2015).

    CAS  Article  Google Scholar 

  26. Harding, K., Wedeen, C., McGinnis, W. & Levine, M. Spatially regulated expression of homeotic genes in Drosophila. Science 229, 1236–1242 (1985).

    CAS  Article  Google Scholar 

  27. Akam, M. The molecular basis for metameric pattern in the Drosophila embryo. Development 101, 1–22 (1987).

    CAS  PubMed  Google Scholar 

  28. Schmidt, K. & Starck, J. M. Testing evolutionary hypotheses about the phylotypic period of zebrafish. J. Exp. Zool. B 316, 319–329 (2011).

    Article  Google Scholar 

  29. Rebeiz, M., Jikomes, N., Kassner, V. A. & Carroll, S. B. Evolutionary origin of a novel gene expression pattern through co-option of the latent activities of existing regulatory sequences. Proc. Natl Acad. Sci. USA 108, 10036–10043 (2011).

    CAS  Article  Google Scholar 

  30. Halligan, D. L. & Keightley, P. D. Spontaneous mutation accumulation studies in evolutionary genetics. Annu. Rev. Ecol. Evol. System. 40, 151–172 (2009).

    Article  Google Scholar 

  31. Baer, C. F. et al. Comparative evolutionary genetics of spontaneous mutations affecting fitness in rhabditid nematodes. Proc. Natl Acad. Sci. USA 102, 5785–5790 (2005).

    CAS  Article  Google Scholar 

  32. Levin, M. et al. The mid-developmental transition and the evolution of animal body plans. Nature 531, 637–641 (2016).

    CAS  Article  Google Scholar 

  33. Hashimshony, T., Feder, M., Levin, M., Hall, B. K. & Yanai, I. Spatiotemporal transcriptomics reveals the evolutionary history of the endoderm germ layer. Nature 519, 219–222 (2015).

    CAS  Article  Google Scholar 

  34. Stoltzfus, A. & Yampolsky, L. Y. Climbing Mount Probable: mutation as a cause of nonrandomness in evolution. J. Hered. 100, 637–647 (2009).

    CAS  Article  Google Scholar 

  35. Gilbert, S. F. Developmental Biology 6th edn (Sinauer, 2000).

    Google Scholar 

  36. Yanai, I., Peshkin, L., Jorgensen, P. & Kirschner, M. W. Mapping gene expression in two Xenopus species: evolutionary constraints and developmental flexibility. Dev. Cell 20, 483–496 (2011).

    CAS  Article  Google Scholar 

  37. Gerstein, M. B. et al. Comparative analysis of the transcriptome across distant species. Nature 512, 445–448 (2014).

    CAS  Article  Google Scholar 

  38. Estes, S. & Lynch, M. Rapid fitness recovery in mutationally degraded lines of Caenorhabditis elegans. Evolution 57, 1022–1030 (2003).

    Article  Google Scholar 

  39. Baugh, L. R., Hill, A. A., Slonim, D. K., Brown, E. L. & Hunter, C. P. Composition and dynamics of the Caenorhabditis elegans early embryonic transcriptome. Development 130, 889–900 (2003).

    CAS  Article  Google Scholar 

  40. Baker, S. C. et al. The External RNA Controls Consortium: a progress report. Nat. Methods 2, 731–734 (2005).

    CAS  Article  Google Scholar 

  41. Hashimshony, T., Wagner, F., Sher, N. & Yanai, I. CEL-Seq: single-cell RNA-Seq by multiplexed linear amplification. Cell Rep. 2, 666–673 (2012).

    CAS  Article  Google Scholar 

  42. Hashimshony, T. et al. CEL-Seq2: sensitive highly-multiplexed single-cell RNA-Seq. Genome Biol. 17, 77 (2016).

    Article  Google Scholar 

  43. Langmead, B., Trapnell, C., Pop, M. & Salzberg, S. L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009).

    Article  Google Scholar 

  44. Anders, S., Pyl, P. T. & Huber, W. HTSeq — a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166–169 (2015).

    CAS  Article  Google Scholar 

  45. Howe, K. L. et al. WormBase 2016: expanding to enable helminth genomic research. Nucl. Acids Res. 44, D774–D780 (2016).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank C. F. Baer of the University of Florida at Gainesville for providing the mutation accumulation strains and for his comments. We thank J. F. Ryan from the Whitney Institute for Marine Bioscience for comments. We also thank members of our laboratory for constructive comments. We thank the Technion Genome Center for technical assistance.

Author information

Authors and Affiliations

Authors

Contributions

H.Z. and I.Y. conceived and designed the project. H.Z. led the collection of samples, the processing of the samples for CEL-Seq and the initial bioinformatics. Both authors analysed the data and wrote the manuscript.

Corresponding author

Correspondence to Itai Yanai.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Figures 1–4; Supplementary Table 1. (PDF 3985 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zalts, H., Yanai, I. Developmental constraints shape the evolution of the nematode mid-developmental transition. Nat Ecol Evol 1, 0113 (2017). https://doi.org/10.1038/s41559-017-0113

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41559-017-0113

Further reading

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