Toward a Theory of Multilevel Evolution: Long-Term Information Integration Shapes the Mutational Landscape and Enhances Evolvability

  • Paulien HogewegEmail author
Part of the Advances in Experimental Medicine and Biology book series (volume 751)


Most of evolutionary theory has abstracted away from how information is coded in the genome and how this information is transformed into traits on which selection takes place. While in the earliest stages of biological evolution, in the RNA world, the mapping from the genotype into function was largely predefined by the physical–chemical properties of the evolving entities (RNA replicators, e.g. from sequence to folded structure and catalytic sites), in present-day organisms, the mapping itself is the result of evolution. I will review results of several in silico evolutionary studies which examine the consequences of evolving the genetic coding, and the ways this information is transformed, while adapting to prevailing environments. Such multilevel evolution leads to long-term information integration. Through genome, network, and dynamical structuring, the occurrence and/or effect of random mutations becomes nonrandom, and facilitates rapid adaptation. This is what does happen in the in silico experiments. Is it also what did happen in biological evolution? I will discuss some data that suggest that it did. In any case, these results provide us with novel search images to tackle the wealth of biological data.


Long Terminal Repeat Transcription Factor Binding Site High Fitness High Mutation Rate Fitness Landscape 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



I thank my (former) students, in particular Nobuto Takeuchi, Anton Crombach, Otto Corderro, and Thomas Cuypers. I reviewed their work in this chapter, and I thoroughly enjoyed working with them! I also thank my longtime collaborator Ben Hesper for his strong conceptual support.


  1. 1.
    Adami C, Ofria C, Collier TC (2000) Evolution of biological complexity. Proc Natl Acad Sci 97(9):4463PubMedCrossRefGoogle Scholar
  2. 2.
    Barabási AL, Albert R (1999) Emergence of scaling in random networks. Science 286(5439):509PubMedCrossRefGoogle Scholar
  3. 3.
    Boerlijst M, Hogeweg P (1992) Self-structuring and selection: Spiral waves as a substrate for prebiotic evolution. In: In: Langton CG, Taylor C, Farmer JD, Rasmussen S (eds) Artificial Life II pp. 255–276Google Scholar
  4. 4.
    Boerlijst MC, Hogeweg P (1991) Spiral wave structure in pre-biotic evolution: Hypercycles stable against parasites. Phys D Nonlin Phenom 48(1):17–28CrossRefGoogle Scholar
  5. 5.
    Ciliberti S, Martin OC, Wagner A (2007) Innovation and robustness in complex regulatory gene networks. Proc Natl Acad Sci 104(34):13591PubMedCrossRefGoogle Scholar
  6. 6.
    Cordero OX, Hogeweg P (2006) Feed-forward loop circuits as a side effect of genome evolution. Mol Biol Evol 23(10):1931PubMedCrossRefGoogle Scholar
  7. 7.
    Crick F (1971) Central dogma of molecular biology. Tsitologiia 13(7):906Google Scholar
  8. 8.
    Crombach A, Hogeweg P (2007) Chromosome rearrangements and the evolution of genome structuring and adaptability. Mol Biol Evol 24(5):1130PubMedCrossRefGoogle Scholar
  9. 9.
    Crombach A, Hogeweg P (2008) Evolution of evolvability in gene regulatory networks. PLoS Comput Biol 4(7):e1000112PubMedCrossRefGoogle Scholar
  10. 10.
    Cuypers TD, Hogeweg P (2012) Virtual genomes in flux: An interplay of neutrality and adaptability explains genome expansion and streamlining. Genome Biol Evol 4(3):212–229PubMedCrossRefGoogle Scholar
  11. 11.
    David LA, Alm EJ (2011) Rapid evolutionary innovation during an archaean genetic expansion. Nature 480(7376):241–244PubMedCrossRefGoogle Scholar
  12. 12.
    de Boer F, Hogeweg P (2010) Eco-evolutionary dynamics, coding structure and the information threshold. BMC Evol Biol 10(1):361PubMedCrossRefGoogle Scholar
  13. 13.
    Draghi J, Wagner GP (2009) The evolutionary dynamics of evolvability in a gene network model. J Evol Biol 22(3):599–611PubMedCrossRefGoogle Scholar
  14. 14.
    Draghi JA, Parsons TL, Wagner GP, Plotkin JB (2010) Mutational robustness can facilitate adaptation. Nature 463(7279):353–355PubMedCrossRefGoogle Scholar
  15. 15.
    Dunham MJ, Badrane H, Ferea T, Adams J, Brown PO, Rosenzweig F, Botstein D (2002) Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae. Proc Natl Acad Sci 99(25):16144PubMedCrossRefGoogle Scholar
  16. 16.
    Ferea TL, Botstein D, Brown PO, Rosenzweig RF (1999) Systematic changes in gene expression patterns following adaptive evolution in yeast. Proc Natl Acad Sci 96(17):9721PubMedCrossRefGoogle Scholar
  17. 17.
    Ferrada E, Wagner A (2008) Protein robustness promotes evolutionary innovations on large evolutionary time-scales. Proc Roy Soc B Biol Sci 275(1643):1595CrossRefGoogle Scholar
  18. 18.
    Fontana W (2002) Modelling  evo-devo with RNA. BioEssays 24(12):1164–1177PubMedCrossRefGoogle Scholar
  19. 19.
    Fontana W, Schuster P (1998) Continuity in evolution: on the nature of transitions. Science 280(5368):1451PubMedCrossRefGoogle Scholar
  20. 20.
    Fontana W, Stadler PF, Bornberg-Bauer EG, Griesmacher T, Hofacker IL, Tacker M, Tarazona P, Weinberger ED, Schuster P (1993) RNA folding and combinatory landscapes. Phys Rev E 47(3):2083–2099CrossRefGoogle Scholar
  21. 21.
    Francino MP (2005) An adaptive radiation model for the origin of new gene functions. Nat Genet 37(6):573PubMedCrossRefGoogle Scholar
  22. 22.
    Grüner W, Giegerich R, Strothmann D, Reidys C, Weber J, Hofacker IL, Stadler PF, Schuster P (1996) Analysis of rna sequence structure maps by exhaustive enumeration I. Neutral networks. Monatsh Chem Chem Mon 127(4):355–374Google Scholar
  23. 23.
    Hahn MW, Han MV, Han SG (2007) Gene family evolution across 12 drosophila genomes. PLoS Genet 3(11):e197PubMedCrossRefGoogle Scholar
  24. 24.
    Hogeweg P (2011) The roots of bioinformatics in theoretical biology. PLoS Comput Biol 7(3):e1002021PubMedCrossRefGoogle Scholar
  25. 25.
    Hogeweg P, Hesper B (1984) Energy directed folding of rna sequences. Nucleic Acids Res 12(1 Pt 1):67PubMedCrossRefGoogle Scholar
  26. 26.
    Hogeweg P, Hesper B (1989) An adaptive, selfmodifying, non goal directed modelling methodology. In: Elzas MS, Oren TI, Zeigler BP (eds) Knowledge systems paradigms. Elsevier Science, North Holland, pp 77–92Google Scholar
  27. 27.
    Hogeweg P, Takeuchi N (2003) Multilevel selection in models of prebiotic evolution: compartments and spatial self-organization. Orig Life Evol Biosph 33(4):375–403PubMedCrossRefGoogle Scholar
  28. 28.
    Holland LZ, Albalat R, Azumi K, Benito-Gutiérrez È, Blow MJ, Bronner-Fraser M, Brunet F, Butts T, Candiani S, Dishaw LJ et al (2008) The amphioxus genome illuminates vertebrate origins and cephalochordate biology. Genome Res 18(7):1100PubMedCrossRefGoogle Scholar
  29. 29.
    Hurst LD, Pál C, Lercher MJ (2004) The evolutionary dynamics of eukaryotic gene order. Nat Rev Genet 5(4):299–310PubMedCrossRefGoogle Scholar
  30. 30.
    Huynen MA (1996) Exploring phenotype space through neutral evolution. J Mol Evol 43(3):165–169PubMedCrossRefGoogle Scholar
  31. 31.
    Huynen MA, Hogeweg P (1994) Pattern generation in molecular evolution: Exploitation of the variation in RNA landscapes. J Mol Evol 39(1):71–79PubMedCrossRefGoogle Scholar
  32. 32.
    Huynen MA, Stadler PF, Fontana W (1996) Smoothness within ruggedness: The role of neutrality in adaptation. Proc Natl Acad Sci USA 93(1):397PubMedCrossRefGoogle Scholar
  33. 33.
    Huynen MA, Snel B, Bork P, Gibson TJ (2001) The phylogenetic distribution of frataxin indicates a role in iron-sulfur cluster protein assembly. Hum Mol Genet 10(21):2463PubMedCrossRefGoogle Scholar
  34. 34.
    Kacser H, Beeby R (1984) Evolution of catalytic proteins. J Mol Evol 20(1):38–51PubMedCrossRefGoogle Scholar
  35. 35.
    Kashtan N, Itzkovitz S, Milo R, Alon U (2004) Topological generalizations of network motifs. Phys Rev E 70(3):031909CrossRefGoogle Scholar
  36. 36.
    Kauffman S, Levin S (1987) Toward a general theory of adaptive walks on rugged landscapes*. J Theor Biol 128(1):11–45PubMedCrossRefGoogle Scholar
  37. 37.
    Kim WK, Marcotte EM (2008) Age-dependent evolution of the yeast protein interaction network suggests a limited role of gene duplication and divergence. PLoS Comput Biol 4(11):e1000232PubMedCrossRefGoogle Scholar
  38. 38.
    Kimura M (1983) The neutral theory of molecular evolution. Cambridge University Press, CambridgeCrossRefGoogle Scholar
  39. 39.
    Koonin EV (2011) Are there laws of genome evolution? PLoS Comput Biol 7(8):e1002173PubMedCrossRefGoogle Scholar
  40. 40.
    Lynch M (2007) The origins of genome architecture. Sinauer Associates, SunderlandGoogle Scholar
  41. 41.
    Lynch M, Conery JS (2003) The origins of genome complexity. Science 302(5649):1401Google Scholar
  42. 42.
    May RM (2004) Uses and abuses of mathematics in biology. Science 303(5659):790PubMedCrossRefGoogle Scholar
  43. 43.
    Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U (2002) Network motifs: simple building blocks of complex networks. Science 298(5594):824PubMedCrossRefGoogle Scholar
  44. 44.
    Neyfakh AA, Baranova NN, Mizrokhi LJ (2006) A system for studying evolution of life-like virtual organisms. Biol Direct 1(1):23PubMedCrossRefGoogle Scholar
  45. 45.
    Pagie L, Hogeweg P (1997) Evolutionary consequences of coevolving targets. Evol Comput 5(4):401–418PubMedCrossRefGoogle Scholar
  46. 46.
    Pál C, Hurst LD (2003) Evidence for co-evolution of gene order and recombination rate. Nat Genet 33(3):392–395PubMedCrossRefGoogle Scholar
  47. 47.
    Pastor-Satorras R, Smith E, Solé RV (2003) Evolving protein interaction networks through gene duplication. J Theor Biol 222(2):199–210PubMedCrossRefGoogle Scholar
  48. 48.
    Renner A, Bornberg-Bauer E (1997) Exploring the fitness landscapes of lattice proteins. Pac Symp Biocomput 361–372Google Scholar
  49. 49.
    Romero PA, Arnold FH (2009) Exploring protein fitness landscapes by directed evolution. Nat Rev Mol Cell Biol 10(12):866–876PubMedCrossRefGoogle Scholar
  50. 50.
    Savill NJ, Rohandi P, Hogeweg P (1997) Self-reinforcing spatial patterns enslave evolution in a host-parasitoid system. J Theor Biol 188:11–20PubMedCrossRefGoogle Scholar
  51. 51.
    Scharloo W (1991) Canalization: genetic and developmental aspects. Annu Rev Ecol Systemat 22:65–93CrossRefGoogle Scholar
  52. 52.
    Schultes EA, Bartel DP (2000) One sequence, two ribozymes: Implications for the emergence of new ribozyme folds. Science 289(5478):448PubMedCrossRefGoogle Scholar
  53. 53.
    Schuster P, Fontana W, Stadler PF, Hofacker IL (1994) From sequences to shapes and back: a case study in RNA secondary structures. Proc Biol Sci 255(1344):279–284PubMedCrossRefGoogle Scholar
  54. 54.
    Shakhnovich BE, Deeds E, Delisi C, Shakhnovich E (2005) Protein structure and evolutionary history determine sequence space topology. Genome Res 15(3):385PubMedCrossRefGoogle Scholar
  55. 55.
    Smith JM, Szathmáry E (1997) The major transitions in evolution. Oxford University Press, OxfordGoogle Scholar
  56. 56.
    Takeuchi N, Hogeweg P (2008) Evolution of complexity in RNA-like replicator systems. Biol Direct 3(11). doi:10.1186/1745-6150-3-11Google Scholar
  57. 57.
    Takeuchi N, Hogeweg P (2009) Multilevel selection in models of prebiotic evolution II: a direct comparison of compartmentalization and spatial self-organization. PLoS Comput Biol 5(10):e1000542PubMedCrossRefGoogle Scholar
  58. 58.
    Takeuchi N, Poorthuis P, Hogeweg P (2005) Phenotypic error threshold; additivity and epistasis in rna evolution. BMC Evol Biol 5(1):9PubMedCrossRefGoogle Scholar
  59. 59.
    Takeuchi N, Hogeweg P, Koonin EV (2011) On the origin of dna genomes: evolution of the division of labor between template and catalyst in model replicator systems. PLoS Comput Biol 7(3):e1002024PubMedCrossRefGoogle Scholar
  60. 60.
    ten Tusscher K, Hogeweg P (2009) The role of genome and gene regulatory network canalization in the evolution of multi-trait polymorphisms and sympatric speciation. BMC Evol Biol 9(1):159PubMedCrossRefGoogle Scholar
  61. 61.
    Van Der Laan JD, Hogeweg P (1995) Predator-prey coevolution: Interactions among different time scales. Proc Roy Soc Lond B 259:35–42CrossRefGoogle Scholar
  62. 62.
    Van Hoek MJA, Hogeweg P (2006) In silico evolved lac operons exhibit bistability for artificial inducers, but not for lactose. Biophys J 91(8):2833–2843PubMedCrossRefGoogle Scholar
  63. 63.
    Van Nimwegen E, Crutchfield JP (2000) Metastable evolutionary dynamics: crossing fitness barriers or escaping via neutral paths? Bull Math Biol 62(5):799–848PubMedCrossRefGoogle Scholar
  64. 64.
    Van Nimwegen E, Crutchfield JP, Huynen M (1999) Neutral evolution of mutational robustness. Proc Natl Acad Sci USA 96(17):9716PubMedCrossRefGoogle Scholar
  65. 65.
    Van Noort V, Snel B, Huynen MA (2004) The yeast coexpression network has a small-world, scale-free architecture and can be explained by a simple model. EMBO Rep 5(3):280–284PubMedCrossRefGoogle Scholar
  66. 66.
    Wagner A (2005) Robustness and evolvability in living systems. Princeton University Press, PrincetonGoogle Scholar
  67. 67.
    Wagner A (2008) Neutralism and selectionism: a network-based reconciliation. Nat Rev Genet 9(12):965–974PubMedCrossRefGoogle Scholar
  68. 68.
    Wagner A (2008) Robustness and evolvability: a paradox resolved. Proc Roy Soc B Biol Sci 275(1630):91CrossRefGoogle Scholar
  69. 69.
    Wagner A (2011) The origins of evolutionary innovations: a theory of transformative change in living systems. Oxford University Press, OxfordGoogle Scholar
  70. 70.
    Wloch DM, Szafraniec K, Borts RH, Korona R (2001) Direct estimate of the mutation rate and the distribution of fitness effects in the yeast saccharomyces cerevisiae. Genetics 159(2):441PubMedGoogle Scholar
  71. 71.
    Wright S (1932) The roles of mutation, inbreeding, crossbreeding and selection in evolution. Proc 6th Int Cong Genet 1:356–366Google Scholar
  72. 72.
    Zuckerkandl E (1997) Neutral and nonneutral mutations: the creative mix; evolution of complexity in gene interaction systems. J Mol Evol 44:2–8CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Theoretical Biology and Bioinformatics GroupUtrecht UniversityUtrechtThe Netherlands

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