Short-time evolution in the adaptive immune system.

We exploit a simple model to numerically and analytically investigate the effect of enforcing a time constraint for achieving a system-wide goal during an evolutionary dynamics. This situation is relevant to finding antibody specificities in the adaptive immune response as well as to artificial situations in which an evolutionary dynamics is used to generate a desired capability in a limited number of generations. When the likelihood of finding the target phenotype is low, we find that the optimal mutation rate can exceed the error threshold, in contrast to conventional evolutionary dynamics. We also show how a logarithmic correction to the usual inverse scaling of population size with mutation rate arises. Implications for natural and artificial evolutionary situations are discussed.

[1]  Andrew G. Glen,et al.  APPL , 2001 .

[2]  Stefan Bornholdt,et al.  Coevolution of quasispecies: B-cell mutation rates maximize viral error catastrophes. , 2001, Physical review letters.

[3]  H. Levine,et al.  Optimal Strategy for Competence Differentiation in Bacteria , 2010, PLoS genetics.

[4]  Akira Oyama,et al.  Real-coded adaptive range genetic algorithm applied to transonic wing optimization , 2000, Appl. Soft Comput..

[5]  Garnett Kelsoe,et al.  Predicted and inferred waiting times for key mutations in the germinal centre reaction: Evidence for stochasticity in selection , 1998, Immunology and cell biology.

[6]  M. Eigen,et al.  Molecular quasi-species. , 1988 .

[7]  Michael W. Deem,et al.  LOCALIZATION AND GLASSY DYNAMICS IN THE IMMUNE SYSTEM , 2006 .

[8]  Alan S. Perelson,et al.  The Evolution of Emergent Organization in Immune System Gene Libraries , 1995, ICGA.

[9]  M. Deem,et al.  Quasispecies theory for multiple-peak fitness landscapes. , 2006, Physical review. E, Statistical, nonlinear, and soft matter physics.

[10]  J. Edwards,et al.  B-cell targeting in rheumatoid arthritis and other autoimmune diseases , 2006, Nature Reviews Immunology.

[11]  K. Rajewsky,et al.  The repertoire of somatic antibody mutants accumulating in the memory compartment after primary immunization is restricted through affinity maturation and mirrors that expressed in the secondary response , 1990, The Journal of experimental medicine.

[12]  David G. Schatz,et al.  Targeting of somatic hypermutation , 2006, Nature Reviews Immunology.

[13]  Chin-Kun Hu,et al.  Self-organizing behavior in a lattice model for co-evolution of virus and immune systems. , 2007, Physical review. E, Statistical, nonlinear, and soft matter physics.

[14]  P. Hajela,et al.  Genetic algorithms in truss topological optimization , 1995 .

[15]  A S Perelson,et al.  Modeling and optimization of populations subject to time-dependent mutation. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[16]  C. Brooks Computer simulation of liquids , 1989 .

[17]  D. Wilson A theory of group selection. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Michael W Deem,et al.  Sequence space localization in the immune system response to vaccination and disease. , 2003, Physical review letters.

[19]  C. Benoist,et al.  Autoimmunity provoked by infection: how good is the case for T cell epitope mimicry? , 2001, Nature Immunology.

[20]  P. Hogeweg,et al.  Error-threshold exists in fitness landscapes with lethal mutants , 2007, BMC Evolutionary Biology.

[21]  T. Wassmer 6 , 1900, EXILE.

[22]  S H Kleinstein,et al.  Toward quantitative simulation of germinal center dynamics: biological and modeling insights from experimental validation. , 2001, Journal of theoretical biology.

[23]  L. McGuinness,et al.  A single-cell pedigree analysis of alternative stochastic lymphocyte fates , 2009, Proceedings of the National Academy of Sciences.

[24]  A. Kang,et al.  Autoimmunity to type II collagen an experimental model of arthritis , 1977, The Journal of experimental medicine.

[25]  L. Wilkinson Immunity , 1891, The Lancet.

[26]  M. Wabl,et al.  Genome-wide somatic hypermutation. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[27]  M. Deem,et al.  A hierarchical approach to protein molecular evolution. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[28]  J. Singh,et al.  Why are there so few key mutant clones? The influence of stochastic selection and blocking on affinity maturation in the germinal center. , 2003, International immunology.

[29]  Michael W Deem,et al.  Spontaneous emergence of modularity in a model of evolving individuals and in real networks. , 2009, Physical review. E, Statistical, nonlinear, and soft matter physics.

[30]  Eugene I. Shakhnovich,et al.  Optimality of Mutation and Selection in Germinal Centers , 2010, PLoS Comput. Biol..

[31]  U. Storb,et al.  Somatic hypermutation of immunoglobulin genes is linked to transcription initiation. , 1996, Immunity.

[32]  D. Nicolae,et al.  Effects of sequence and structure on the hypermutability of immunoglobulin genes. , 2002, Immunity.

[33]  M. Shlomchik,et al.  The Influence of Somatic Mutation on Clonal Expansion , 1989 .

[34]  G. Weisbuch,et al.  A shape space approach to the dynamics of the immune system. , 1990, Journal of theoretical biology.

[35]  L. Staudt,et al.  Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Grant P. Steven,et al.  Structural application of a shape optimization method based on a genetic algorithm , 2001 .

[37]  Claus O Wilke,et al.  Quasispecies theory in the context of population genetics , 2005, BMC Evolutionary Biology.

[38]  Andrew J. McMichael,et al.  Clonal Selection, Clonal Senescence, and Clonal Succession: The Evolution of the T Cell Response to Infection with a Persistent Virus1 , 2002, The Journal of Immunology.

[39]  M. Eigen Selforganization of matter and the evolution of biological macromolecules , 1971, Naturwissenschaften.

[40]  M. Cohn,et al.  The Protection: The Unit of Humoral Immunity Selected by Evolution , 1990, Immunological Reviews.

[41]  Franco Celada,et al.  Affinity maturation and hypermutation in a simulation of the humoral immune response , 1996, European journal of immunology.

[42]  Melinda Fitzgerald,et al.  Immunol. Cell Biol. , 1995 .

[43]  P. Higgs,et al.  Population evolution on a multiplicative single-peak fitness landscape. , 1996, Journal of theoretical biology.

[44]  M. Deem,et al.  Phase diagrams of quasispecies theory with recombination and horizontal gene transfer. , 2006, Physical review letters.

[45]  J. Uhr,et al.  ANTIBODY FORMATION , 1962, The Journal of experimental medicine.