Survival of the sparsest: robust gene networks are parsimonious

Biological gene networks appear to be dynamically robust to mutation, stochasticity, and changes in the environment and also appear to be sparsely connected. Studies with computational models, however, have suggested that denser gene networks evolve to be more dynamically robust than sparser networks. We resolve this discrepancy by showing that misassumptions about how to measure robustness in artificial networks have inadvertently discounted the costs of network complexity. We show that when the costs of complexity are taken into account, that robustness implies a parsimonious network structure that is sparsely connected and not unnecessarily complex; and that selection will favor sparse networks when network topology is free to evolve. Because a robust system of heredity is necessary for the adaptive evolution of complex phenotypes, the maintenance of frugal network complexity is likely a crucial design constraint that underlies biological organization.

[1]  Morley's “Organic Chemistry” , 1886, Nature.

[2]  E. Lewis A gene complex controlling segmentation in Drosophila , 1978, Nature.

[3]  A. Kondrashov Deleterious mutations and the evolution of sexual reproduction , 1988, Nature.

[4]  John H. Holland,et al.  Adaptation in Natural and Artificial Systems: An Introductory Analysis with Applications to Biology, Control, and Artificial Intelligence , 1992 .

[5]  A. Wagner DOES EVOLUTIONARY PLASTICITY EVOLVE? , 1996, Evolution; international journal of organic evolution.

[6]  Alexander V. Spirov,et al.  Graphical interface to the genetic network database GeNet , 1998, Bioinform..

[7]  G. Odell,et al.  The segment polarity network is a robust developmental module , 2000, Nature.

[8]  R. Solé,et al.  Gene networks capable of pattern formation: from induction to reaction-diffusion. , 2000, Journal of theoretical biology.

[9]  Marek S. Skrzypek,et al.  YPDTM, PombePDTM and WormPDTM: model organism volumes of the BioKnowledgeTM Library, an integrated resource for protein information , 2001, Nucleic Acids Res..

[10]  A. Bergman,et al.  Waddington's canalization revisited: Developmental stability and evolution , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[11]  S. Shen-Orr,et al.  Network motifs in the transcriptional regulation network of Escherichia coli , 2002, Nature Genetics.

[12]  Nicola J. Rinaldi,et al.  Transcriptional Regulatory Networks in Saccharomyces cerevisiae , 2002, Science.

[13]  L. Hood,et al.  A Genomic Regulatory Network for Development , 2002, Science.

[14]  Ricard V Solé,et al.  Adaptive walks in a gene network model of morphogenesis: insights into the Cambrian explosion. , 2003, The International journal of developmental biology.

[15]  A. Bergman,et al.  Evolutionary capacitance as a general feature of complex gene networks , 2003, Nature.

[16]  Uri Alon,et al.  Response delays and the structure of transcription networks. , 2003, Journal of molecular biology.

[17]  Carsten Peterson,et al.  Random Boolean network models and the yeast transcriptional network , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[18]  J. Masel,et al.  Genetic assimilation can occur in the absence of selection for the assimilating phenotype, suggesting a role for the canalization heuristic , 2004, Journal of evolutionary biology.

[19]  J. Mattick RNA regulation: a new genetics? , 2004, Nature Reviews Genetics.

[20]  H. Iba,et al.  Reverse engineering genetic networks using evolutionary computation. , 2005, Genome informatics. International Conference on Genome Informatics.

[21]  Kristen K. Dang,et al.  Sexual reproduction selects for robustness and negative epistasis in artificial gene networks , 2006, Nature.

[22]  P. Cluzel,et al.  Effects of topology on network evolution , 2006 .

[23]  R. B. Azevedo,et al.  Sexual reproduction selects for robustness and negative epistasis in artificial gene networks , 2006, Nature.

[24]  G. Almouzni,et al.  Chromatin assembly: a basic recipe with various flavours. , 2006, Current opinion in genetics & development.

[25]  A. Bergman,et al.  Functional and evolutionary inference in gene networks: does topology matter? , 2006, Genetica.

[26]  Qingqiu Gong,et al.  An Arabidopsis gene network based on the graphical Gaussian model. , 2007, Genome research.

[27]  Andreas Wagner,et al.  Robustness Can Evolve Gradually in Complex Regulatory Gene Networks with Varying Topology , 2007, PLoS Comput. Biol..

[28]  S. Henikoff,et al.  Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription , 2007, Nature Genetics.

[29]  A. Bergman,et al.  The limits of subfunctionalization , 2007, BMC Evolutionary Biology.

[30]  Rick Durrett,et al.  Wagner's canalization model. , 2007, Theoretical population biology.

[31]  A. Wagner,et al.  Innovation and robustness in complex regulatory gene networks , 2007, Proceedings of the National Academy of Sciences.

[32]  Aviv Bergman,et al.  Coevolution of robustness, epistasis, and recombination favors asexual reproduction , 2007, Proceedings of the National Academy of Sciences.

[33]  A. Wagner,et al.  Multifunctionality and robustness trade-offs in model genetic circuits. , 2008, Biophysical journal.