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Is the evolution of insulin Darwinian or due to selectively neutral mutation?

Abstract

A model for the evolution of insulin mainly in terms of adaptive processes is discussed. The model depends critically on the relationship of sequence changes to the three-dimensional structure and the role of various parts of this structure in the conversion of the proinsulin molecule to the active form, the storage of insulin, its transport to the site of action and its interaction with a receptor.

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References

  1. Darwinian, Neo-Darwinian Evolution, Proc. sixth Berkeley Symp., 5, (edit. by Le Cam, L. M., Neyman, J., and Scott, E. L.) (University of California Press, Berkeley and Los Angeles, 1972).

  2. Smith, E. L., in The Enzymes (edit. by Boyer, P. D.), 1, 267–314 (Academic New York, 1970).

    Google Scholar 

  3. Kimura, M., Nature, 217, 624–626 (1968).

    Article  ADS  CAS  Google Scholar 

  4. King, J. L., and Jukes, T. H., Science, 164, 788–798 (1969).

    Article  ADS  CAS  Google Scholar 

  5. Markussen, J., and Volund, A., Int. J. Peptide Protein Res., 6, 79–86 (1974).

    Article  CAS  Google Scholar 

  6. Smith, L. F., Diabetes, 21, Suppl. 2, 457–460 (1972).

    Article  CAS  Google Scholar 

  7. Adams, M. J., et al., Nature, 224, 491–495 (1969).

    Article  ADS  CAS  Google Scholar 

  8. Blundell, T. L., Dodson, G. G., Dodson, E. J., Hodgkin, D. C., and Vijayan, M., Rec. Prog. Hormone Res., 27, 1–40 (1971).

    CAS  Google Scholar 

  9. Blundell, T. L., Dodson, G. G., Hodgkin, D. C., and Mercola, D. A., Adv. Protein Chem., 26, 279–402 (1972).

    Article  CAS  Google Scholar 

  10. Steiner, D. F., and Oyer, P. E., Proc. natn. Acad. Sci. U.S.A., 57, 473–480 (1967).

    Article  ADS  CAS  Google Scholar 

  11. Grieder, M. H., Howell, S. L., and Lacy, P. E., J. Cell Biol., 41, 162–166 (1969).

    Article  Google Scholar 

  12. Lange, R. H., Diabetologia, 7, 465–466 (1971).

    Article  CAS  Google Scholar 

  13. Gavin, J. R., III, Gorden, P., Roth, J., Archer, J. A., Buell, D. N., J. biol. Chem., 248, 2202–2207 (1973).

    CAS  PubMed  Google Scholar 

  14. Gammettoft, S., and Gliemann, J., Biochem. biophys. Acta, 320, 16–32 (1973).

    Article  Google Scholar 

  15. Preychett, P., Roth, J., and Neville, D. M., Proc. natn. Acad. Sci. U.S.A., 68, 1833–1837 (1971).

    Article  ADS  Google Scholar 

  16. Falkmer, S., in Ostman, J., Diabetes, Proc. sixth Cong. Int. Diabetes Fed., 55–66 (Excerpta Medica Foundation, Amsterdam, 1969).

    Google Scholar 

  17. Frank, B. H., and Veros, A. J., Biochem. biophys. Res. Commun., 38, 284–289 (1970).

    Article  CAS  Google Scholar 

  18. Grant, P. T., Coombs, T. L., and Franks, B. H., Biochem. J., 126, 433 (1972).

    Article  CAS  Google Scholar 

  19. Baker, E. N., and Dodson, G. G., J. molec. Biol., 54, 605 (1970).

    Article  CAS  Google Scholar 

  20. Cutfield, J. F., Cutfield, S. M., Dodson, E. J., Dodson, G. G., and Sabesan, M. N., J. molec. Biol., 87, 23–30 (1974).

    Article  CAS  Google Scholar 

  21. Peterson, J. D., Coulter, C. L., Steiner, D. F., Emdin, S. O., and Falkmer, S., Nature, 251, 239–240 (1974).

    Article  ADS  CAS  Google Scholar 

  22. Zimmerman, A. E., and Yip, C. C., J. biol. Chem., 249, 4021–4036 (1974).

    CAS  PubMed  Google Scholar 

  23. Wood, S. P., Blundell, T. L., Wollmer, A., Lazarus, N. R., and Neville, R. W. J., Eur. J. Biochem. (in the press).

  24. Neville, R. W. J., Weir, B. J., and Lazarus, N. R., Diabetes, 22, 851–853 (1973).

    Article  CAS  Google Scholar 

  25. Dayhoff, M. O., Atlas of Protein Sequence and Structure, 5, D210–D211 (1972).

    Google Scholar 

  26. Markussen, J., and Sunby, F., Int. J. Peptide Protein Res., 5, 37–38 (1973).

    Article  CAS  Google Scholar 

Download references

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Blundell, T., Wood, S. Is the evolution of insulin Darwinian or due to selectively neutral mutation?. Nature 257, 197–203 (1975). https://doi.org/10.1038/257197a0

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