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Natural variation in a neural globin tunes oxygen sensing in wild Caenorhabditis elegans

Nature volume 458, pages 1030–1033 (2009)Cite this article

Abstract

Behaviours evolve by iterations of natural selection, but we have few insights into the molecular and neural mechanisms involved. Here we show that some Caenorhabditis elegans wild strains switch between two foraging behaviours in response to subtle changes in ambient oxygen. This finely tuned switch is conferred by a naturally variable hexacoordinated globin, GLB-5. GLB-5 acts with the atypical soluble guanylate cyclases1,2,3, which are a different type of oxygen binding protein, to tune the dynamic range of oxygen-sensing neurons close to atmospheric (21%) concentrations. Calcium imaging indicates that one group of these neurons is activated when oxygen rises towards 21%, and is inhibited as oxygen drops below 21%. The soluble guanylate cyclase GCY-35 is required for high oxygen to activate the neurons; GLB-5 provides inhibitory input when oxygen decreases below 21%. Together, these oxygen binding proteins tune neuronal and behavioural responses to a narrow oxygen concentration range close to atmospheric levels. The effect of the glb-5 gene on oxygen sensing and foraging is modified by the naturally variable neuropeptide receptor npr-1 (refs 4, 5), providing insights into how polygenic variation reshapes neural circuit function.

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Figure 1: Polygenic natural variation tunes O 2 responses in wild C. elegans.
Figure 2: Natural variation in a hexacoordinated globin sculpts C. elegans O 2 responses.
Figure 3: glb-5 acts in O 2 sensing neurons.
Figure 4: Responses of O 2 sensing neurons.

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References

  1. Cheung, B. H., Arellano-Carbajal, F., Rybicki, I. & De Bono, M. Soluble guanylate cyclases act in neurons exposed to the body fluid to promote C. elegans aggregation behavior. Curr. Biol. 14, 1105–1111 (2004)

    Article  CAS  Google Scholar 

  2. Gray, J. M. et al. Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue. Nature 430, 317–322 (2004)

    Article  ADS  CAS  Google Scholar 

  3. Cheung, B. H., Cohen, M., Rogers, C., Albayram, O. & de Bono, M. Experience-dependent modulation of C. elegans behavior by ambient oxygen. Curr. Biol. 15, 905–917 (2005)

    Article  CAS  Google Scholar 

  4. de Bono, M. & Bargmann, C. I. Natural variation in a neuropeptide Y receptor homolog modifies social behavior and food response in C. elegans . Cell 94, 679–689 (1998)

    Article  CAS  Google Scholar 

  5. Coates, J. C. & de Bono, M. Antagonistic pathways in neurons exposed to body fluid regulate social feeding in Caenorhabditis elegans . Nature 419, 925–929 (2002)

    Article  ADS  CAS  Google Scholar 

  6. Korol, A., Rashkovetsky, E., Iliadi, K. & Nevo, E. Drosophila flies in “Evolution Canyon” as a model for incipient sympatric speciation. Proc. Natl Acad. Sci. USA 103, 18184–18189 (2006)

    Article  ADS  CAS  Google Scholar 

  7. Valdar, W. et al. Genome-wide genetic association of complex traits in heterogeneous stock mice. Nature Genet. 38, 879–887 (2006)

    Article  CAS  Google Scholar 

  8. Anholt, R. R. & Mackay, T. F. Quantitative genetic analyses of complex behaviours in Drosophila . Nature Rev. Genet. 5, 838–849 (2004)

    Article  CAS  Google Scholar 

  9. Sachidanandam, R. et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409, 928–933 (2001)

    Article  ADS  CAS  Google Scholar 

  10. Bouchard, T. J. J. & McGue, M. Genetic and environmental influences on human psychological differences. J. Neurobiol. 54, 4–45 (2003)

    Article  Google Scholar 

  11. Hodgkin, J. & Doniach, T. Natural variation and copulatory plug formation in Caenorhabditis elegans . Genetics 146, 149–164 (1997)

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Baumgartl, H., Kritzler, K., Zimelka, W. & Zinkler, D. Local PO2 measurements in the environment of submerged soil microarthropods. Acta Oecol. 15, 781–789 (1994)

    Google Scholar 

  13. Wicks, S. R., Yeh, R. T., Gish, W. R., Waterston, R. H. & Plasterk, R. H. Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map. Nature Genet. 28, 160–164 (2001)

    Article  CAS  Google Scholar 

  14. Ota, M., Isogai, Y. & Nishikawa, K. Structural requirement of highly-conserved residues in globins. FEBS Lett. 415, 129–133 (1997)

    Article  CAS  Google Scholar 

  15. Dewilde, S. et al. Biochemical characterization and ligand binding properties of neuroglobin, a novel member of the globin family. J. Biol. Chem. 276, 38949–38955 (2001)

    Article  CAS  Google Scholar 

  16. Trandafir, F. et al. Neuroglobin and cytoglobin as potential enzyme or substrate. Gene 398, 103–113 (2007)

    Article  CAS  Google Scholar 

  17. Yu, S., Avery, L., Baude, E. & Garbers, D. L. Guanylyl cyclase expression in specific sensory neurons: a new family of chemosensory receptors. Proc. Natl Acad. Sci. USA 94, 3384–3387 (1997)

    Article  ADS  CAS  Google Scholar 

  18. Chang, A. J., Chronis, N., Karow, D. S., Marletta, M. A. & Bargmann, C. I. A distributed chemosensory circuit for oxygen preference in C. elegans . PLoS Biol. 4, e274 (2006)

    Article  Google Scholar 

  19. Rogers, C., Persson, A., Cheung, B. & de Bono, M. Behavioral motifs and neural pathways coordinating O2 responses and aggregation in C. elegans . Curr. Biol. 16, 649–659 (2006)

    Article  CAS  Google Scholar 

  20. Ward, J. P. Oxygen sensors in context. Biochim. Biophys. Acta 1777, 1–14 (2008)

    Article  CAS  Google Scholar 

  21. Hou, S. et al. Myoglobin-like aerotaxis transducers in Archaea and Bacteria. Nature 403, 540–544 (2000)

    Article  ADS  CAS  Google Scholar 

  22. Wakasugi, K., Nakano, T. & Morishima, I. Oxidized human neuroglobin acts as a heterotrimeric Gα protein guanine nucleotide dissociation inhibitor. J. Biol. Chem. 278, 36505–36512 (2003)

    Article  CAS  Google Scholar 

  23. Kitatsuji, C., Kurogochi, M., Nishimura, S., Ishimori, K. & Wakasugi, K. Molecular basis of guanine nucleotide dissociation inhibitor activity of human neuroglobin by chemical cross-linking and mass spectrometry. J. Mol. Biol. 368, 150–160 (2007)

    Article  CAS  Google Scholar 

  24. Hoogewijs, D. et al. Wide diversity in structure and expression profiles among members of the Caenorhabditis elegans globin protein family. BMC Genomics 8, 356 (2007)

    Article  Google Scholar 

  25. Sulston, J. & Hodgkin, J. in The Nematode Caenorhabditis Elegans (ed. Wood, W. B.) 587–606 (Cold Spring Harbour Laboratory Press, 1988)

    Google Scholar 

  26. Kerr, R. A. & Schafer, W. R. Intracellular Ca2+ imaging in C. elegans . Methods Mol. Biol. 351, 253–264 (2006)

    CAS  PubMed  Google Scholar 

  27. Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning: a Laboratory Manual (Cold Spring Harbour Laboratory Press, 1989)

    Google Scholar 

  28. Oka, T., Toyomura, T., Honjo, K., Wada, Y. & Futai, M. Four subunit aisoforms of Caenorhabditis elegans vacuolar H+-ATPase. Cell-specific expression during development. J. Biol. Chem. 276, 33079–33085 (2001)

    Article  CAS  Google Scholar 

  29. Okkema, P. G., Harrison, S. W., Plunger, V., Aryana, A. & Fire, A. Sequencerequirements for myosin gene expression and regulation in Caenorhabditis elegans . Genetics 135, 385–404 (1993)

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Mello, C. C., Kramer, J. M., Stinchcomb, D. & Ambros, V. Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J. 10, 3959–3970 (1991)

    Article  CAS  Google Scholar 

  31. Antonini, E. & Brunori, M. Frontiers of Biology (Elsevier, 1971)

    Google Scholar 

  32. Bennett-Lovsey, R. M., Herbert, A. D., Sternberg, M. J. & Kelley, L. A. Exploring the extremes of sequence/structure space with ensemble fold recognition in the program Phyre. Proteins 70, 611–625 (2008)

    Article  CAS  Google Scholar 

  33. Arnold, K., Bordoli, L., Kopp, J. & Schwede, T. The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 22, 195–201 (2006)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank the Caenorhabditis Genetics Center, A. Chisholm, M.-A. Felix and E. Dolgin for C. elegans strains, A. Couto, B. Olofsson, I. Rabinovitch and K. Weber for comments on the manuscript, and I. Johnston and C. Tan for microfluidic devices. This work was supported by the Medical Research Council, a Human Frontier Science Program (HFSP) long-term fellowship (E.G.) and program grant (M.d.B.), the EU Marie Curie Actions (K.E.B.), the European Molecular Biology Organization (K.E.B. and P.L.) and the Fondation Wiener–Anspach (P.L.).

Author Contributions A.P., H.B. and M.d.B. identified glb-5; E.G. determined the glb-5 expression pattern, performed transgenic rescues, and did all biochemistry; P.L. and K.E.B. contributed equally to Ca2+ imaging. M.d.B wrote the text with contributed ideas and discussion from all authors.

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Author notes

  1. Annelie Persson and Einav Gross: These authors contributed equally to this work.

Authors and Affiliations

  1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK ,

    Annelie Persson, Einav Gross, Patrick Laurent, Karl Emanuel Busch, Hugo Bretes & Mario de Bono

  2. Department of Cell and Molecular Biology, Göteborg University, 405 30 Göteborg, Sweden

    Annelie Persson

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Correspondence to Mario de Bono.

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Persson, A., Gross, E., Laurent, P. et al. Natural variation in a neural globin tunes oxygen sensing in wild Caenorhabditis elegans. Nature 458, 1030–1033 (2009). https://doi.org/10.1038/nature07820

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