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. 1989 Aug;86(16):6191–6195. doi: 10.1073/pnas.86.16.6191

Protein evolution on rugged landscapes.

C A Macken 1, A S Perelson 1
PMCID: PMC297803  PMID: 2762321

Abstract

We analyze a mathematical model of protein evolution in which the evolutionary process is viewed as hill-climbing on a random fitness landscape. In studying the structure of such landscapes, we note that a large number of local optima exist, and we calculate the time and number of mutational changes until a protein gets trapped at a local optimum. Such a hill-climbing process may underlie the evolution of antibody molecules by somatic hypermutation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berek C., Milstein C. Mutation drift and repertoire shift in the maturation of the immune response. Immunol Rev. 1987 Apr;96:23–41. doi: 10.1111/j.1600-065x.1987.tb00507.x. [DOI] [PubMed] [Google Scholar]
  2. Bothwell A. L., Paskind M., Reth M., Imanishi-Kari T., Rajewsky K., Baltimore D. Somatic variants of murine immunoglobulin lambda light chains. Nature. 1982 Jul 22;298(5872):380–382. doi: 10.1038/298380a0. [DOI] [PubMed] [Google Scholar]
  3. Chien N. C., Pollock R. R., Desaymard C., Scharff M. D. Point mutations cause the somatic diversification of IgM and IgG2a antiphosphorylcholine antibodies. J Exp Med. 1988 Mar 1;167(3):954–973. doi: 10.1084/jem.167.3.954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clarke S. H., Huppi K., Ruezinsky D., Staudt L., Gerhard W., Weigert M. Inter- and intraclonal diversity in the antibody response to influenza hemagglutinin. J Exp Med. 1985 Apr 1;161(4):687–704. doi: 10.1084/jem.161.4.687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Crews S., Griffin J., Huang H., Calame K., Hood L. A single VH gene segment encodes the immune response to phosphorylcholine: somatic mutation is correlated with the class of the antibody. Cell. 1981 Jul;25(1):59–66. doi: 10.1016/0092-8674(81)90231-2. [DOI] [PubMed] [Google Scholar]
  6. Fontana W., Schuster P. A computer model of evolutionary optimization. Biophys Chem. 1987 May 9;26(2-3):123–147. doi: 10.1016/0301-4622(87)80017-0. [DOI] [PubMed] [Google Scholar]
  7. Kauffman S., Levin S. Towards a general theory of adaptive walks on rugged landscapes. J Theor Biol. 1987 Sep 7;128(1):11–45. doi: 10.1016/s0022-5193(87)80029-2. [DOI] [PubMed] [Google Scholar]
  8. Kocks C., Rajewsky K. Stepwise intraclonal maturation of antibody affinity through somatic hypermutation. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8206–8210. doi: 10.1073/pnas.85.21.8206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. McKean D., Huppi K., Bell M., Staudt L., Gerhard W., Weigert M. Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin. Proc Natl Acad Sci U S A. 1984 May;81(10):3180–3184. doi: 10.1073/pnas.81.10.3180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Panka D. J., Mudgett-Hunter M., Parks D. R., Peterson L. L., Herzenberg L. A., Haber E., Margolies M. N. Variable region framework differences result in decreased or increased affinity of variant anti-digoxin antibodies. Proc Natl Acad Sci U S A. 1988 May;85(9):3080–3084. doi: 10.1073/pnas.85.9.3080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Roberts S., Cheetham J. C., Rees A. R. Generation of an antibody with enhanced affinity and specificity for its antigen by protein engineering. Nature. 1987 Aug 20;328(6132):731–734. doi: 10.1038/328731a0. [DOI] [PubMed] [Google Scholar]
  12. Rudikoff S., Giusti A. M., Cook W. D., Scharff M. D. Single amino acid substitution altering antigen-binding specificity. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1979–1983. doi: 10.1073/pnas.79.6.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sablitzky F., Wildner G., Rajewsky K. Somatic mutation and clonal expansion of B cells in an antigen-driven immune response. EMBO J. 1985 Feb;4(2):345–350. doi: 10.1002/j.1460-2075.1985.tb03635.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Smith J. M. Natural selection and the concept of a protein space. Nature. 1970 Feb 7;225(5232):563–564. doi: 10.1038/225563a0. [DOI] [PubMed] [Google Scholar]
  15. Spetner L. M. Natural selection versus gene uniqueness. Nature. 1970 Jun 6;226(5249):948–949. doi: 10.1038/226948a0. [DOI] [PubMed] [Google Scholar]
  16. Wysocki L., Manser T., Gefter M. L. Somatic evolution of variable region structures during an immune response. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1847–1851. doi: 10.1073/pnas.83.6.1847. [DOI] [PMC free article] [PubMed] [Google Scholar]

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