Biological robustness: Paradigms, mechanisms, systems principles

Frontiers in Genetics

Volumn 3, Issue MAY, 2012, Pages

  Whitacre, James Michael ^a  

^a VRIJE UNIVERSITEIT BRUSSEL   (Belgium)

Author keywords

Biochemical networks; Bow tie; Canalization; Degeneracy; Evolution; Homeostasis; Redundancy; Robustness

Indexed keywords

EID: 84867635448     PISSN: None     EISSN: 16648021     Source Type: Journal    
DOI: 10.3389/fgene.2012.00067     Document Type: Review

References (153)

1. Agrawal,A. A. (2001). Phenotypic plasticity in the interactions and evolution of species. Science 294,321-326.
2. Aldana, M., Balleza, E., Kauffman, S., and Resendiz, O. (2007). Robustness and evolvability in genetic regulatory networks. J. Theor. Biol. 245, 433-448.
3. Alderson, D. L., and Doyle, J. C. (2010). Contrasting views of complexity and their implications for network-centric infrastructures. IEEE Trans. Syst. Man Cybern. A Syst. Hum. 40, 839-852.
4. Almaas, E., Kovács, B., Vicsek, T., Oltvai,Z.N.,and Barabási,A. L. (2004). Global organization of metabolic fluxes in the bacterium Escherichia coli. Nature 427, 839-843.
5. Alon, U., Surette, M. G., Barkai, N., and Leibler, S. (1999). Robustness in bacterial chemotaxis. Nature 397, 168-171.
6. Ancel, L. W., and Fontana, W. (2000). Plasticity, evolvability, and modularity in RNA. J. Exp. Zool. 288, 242-283.
7. Ashby, W. R. (1964). An Introduction to Cybernetics. London: Methuen.
8. Atamas, S. (2005). Les affinités electives. Pour la Science 46, 39-43.
9. Babajide, A., Hofacker, I. L., Sippl, M. J., and Stadler, P. F. (1997). Neutral networks in protein space: a computational study based on knowledge-based potentials of mean force. Fold. Des. 2,261-269.
10. Bak, P., and Paczuski, M. (1995). Complexity, contingency, and criticality. Proc. Natl. Acad. Sci. U.S.A. 92, 6689-6696.
11. Barabási, A. L., and Albert, R. (1999). Emergence of scaling in random networks. Science 286, 509-512.
12. Barkai, N., and Leibler, S. (1997). Robustness in simple biochemical networks. Nature 387, 913-917.
13. Bender, A., and Whitacre, J. M. (2011). Emergent flexibility as a strategy for addressing long-term planning uncertainty, in NATO Risk-Based Planning Conference, Salisbury.
14. Berlow, E. L. (1999). Strong effects of weak interactions in ecological communities. Nature 398, 330-334.
15. Bettis,R. A., andHitt,M. A. (1995). The new competitive landscape. Strateg. Manag. J. 16, 7-19.
16. Bloom, J. D., Labthavikul, S. T., Otey, C. R., and Arnold, F. H. (2006). Protein stability promotes evolvability. Proc. Natl. Acad. Sci. U.S.A. 103, 5869.
17. Braendle, C., and Félix, M. A. (2008). Plasticity and errors of a robust developmental system in different environments. Dev. Cell 15, 714-724.
18. Buchman, T. G. (2002). The community of the self. Nature 420,246-251.
19. Carlson, J. M., and Doyle, J. (2002). Complexity and robustness. Proc. Natl. Acad. Sci. U.S.A. 99, 2538-2545.
20. Chandra, F. A., Buzi, G., and Doyle, J. C. (2011). Glycolytic oscillations and limits on robust efficiency. Science 333, 187.
21. Ciliberti, S., Martin, O. C., and Wagner, A. (2007). Innovation and robustness in complex regulatory gene networks. Proc. Natl. Acad. Sci. U.S.A. 104,13591-13596.
22. Clark, E., Nellis, A., Hickinbotham, S., Stepney, S., Clarke, T., Pay, M., and Young, P. (2011). Degeneracy enriches artificial chemistry binding systems, in European Conference on Artificial Life, Paris.
23. Coelho, P. M. B. M., Salvador, A., and Savageau, M. A. (2009). Quantifying global tolerance of biochemical systems: design implications for moiety-transfer cycles. PLoS Comput. Biol. 5, e1000319. doi:10.1371/journal.pcbi.1000319
24. Conant, G. C., and Wagner, A. (2004). Duplicate genes and robustness to transient gene knock-downs in Caenorhabditis elegans. Proc. Biol. Sci. 271, 89-96.
25. Cowen, L. E., and Lindquist, S. (2005). Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi. Science 309, 2185.
26. Crawford, M. (1992). The hidden costs of accelerated pro duct development. J. Prod. Innov. Manag. 9, 188-199.
27. Crowe, J. H., and Crowe, L. M. (2000). Preservation of mammalian cells-learning nature's tricks. Nat. Biotechnol. 18, 145.
28. Csermely, P. (2004). Strong links are important, but weak links stabilize them. Trends Biochem. Sci. 29, 331-334.
29. Csete, M., and Doyle, J. (2004). Bow ties, metabolism and disease. Trends Biotechnol. 22, 446-450.
30. Dawkins, R. (1983).UniversalDarwinism, in Evolution from Molecules to Man, ed. D. S. Bendall (Cambridge University Press), 202.
31. Dawkins, R. (1999). The Extended Phenotype: The Long Reach of the Gene. Oxford University Press.
32. Day, R., Laland, K. N., and Odling-Smee, F. J. (2003). Rethinking adaptation. Perspect. Biol. Med. 46, 80-95.
33. de Visser, J., Hermisson, J., Wagner, G. P., Ancel Meyers, L., Bagheri-Chaichian, H., Blanchard, J. L., Chao, L., Cheverud, J. M., Elena, S. F., Fontana, W., Gibson, G., Hansen, T. F., Krakauer, D., Lewontin, R. C., Ofria, C., Rice, S. H., von Dassow, G., Wagner, A., and Whitlock, M. C. (2003). Perspective: evolution and detection of genetic robustness. Evolution 57,1959-1972.
34. Dennett, D. (1995). Darwin's Dangerous Idea. New York: Simon & Schuster.
35. Edelman, G. (1987). Neural Darwinism: The Theory of Neuronal Group Selection. New York: Basic Books.
36. Edelman, G. M. (1993). Neural Darwinism: selection and reentrant signaling in higher brain function. Neuron 10,115-125.
37. Edelman, G. M., and Gally, J. A. (2001). Degeneracy and complexity in biological systems. Proc. Natl. Acad. Sci. U.S.A. 98, 13763-13768.
38. Edwards, J. S., and Palsson, B. O. (2000). Robustness analysis of the Escherichia coli metabolic network. Biotechnol. Prog. 16,927-939.
39. Eldar, A., Dorfman, R., Weiss, D., Ashe, H., Shilo, B. Z., and Barkai, N. (2002). Robustness of the BMP morphogen gradient in Drosophila embryonic patterning. Nature 419, 304-308.
40. Espinosa-Soto, C., Padilla-Longoria, P., and Alvarez-Buylla, E. R. (2004). A gene regulatory network model for cell-fate determination during Arabidopsis thaliana flower development that is robust and recovers experimental gene expression profiles. Plant Cell 16, 2923.
41. Featherstone, D., and Broadie, K. (2002). Wrestling with pleiotropy:genomic and topological analysis of the yeast gene expression network. Bioessays 24, 267-274.
42. Feinerman, O., Veiga, J., Dorfman, J. R., Germain, R. N., and Altan-Bonnet, G. (2008). Variability and robustness in T cell activation from regulated heterogeneity in protein levels. Science 321,1081.
43. Félix, M. A., and Wagner, A. (2008). Robustness and evolution: concepts, insights and challenges from a developmental model system. Heredity 100,132-140.
44. Fernandez-Leon, J. A. (2011). Behavioural Robustness and the Distributed Mechanisms Hypothesis. D.Phil. Ph.D. thesis, University of Sussex.
45. Fontana, W., and Schuster, P. (1998). Continuity in evolution: on the nature of transitions. Science 280, 1451-1455.
46. Force, A., Cresko, W. A., Pickett, F. B., Proulx, S. R., Amemiya, C., and Lynch, M. (2005). The origin of subfunctions and modular gene regulation. Genetics 170, 433-446.
47. Frei, R., and Whitacre, J. M. (in press). Degeneracy and networked buffering: principles for supporting emergent evolvability in agile manufacturing systems. J. Nat. Comput.
48. Fu, J., Keurentjes, J. J., Bouwmeester, H., America, T., Verstappen, F. W., Ward, J. L., Beale, M. H., de Vos, R. C., Dijkstra, M., Scheltema, R. A., Johannes, F., Koornneef, M., Vreugdenhil, D., Breitling, R., and Jansen, R. C. (2009). System-wide molecular evidence for phenotypic buffering in Arabidopsis. Nat. Genet. 41, 166-167.
49. Gibson, G., and Dworkin, I. (2004). Uncovering cryptic genetic variation. Nat. Rev. Genet. 5, 681-690.
50. Gómez-Gardenes, J., Moreno, Y., and Floría, L. M. (2005). On the robustness of complex heterogeneous gene expression networks. Biophys. Chem. 115,225-228.
51. Gonze, D., Halloy, J., and Goldbeter, A. (2002). Robustness of circadian rhythms with respect to molecular noise. Proc. Natl. Acad. Sci. U.S.A. 99, 673.
52. Granovetter, M. S. (1973). The strength of weak ties. Am. J. Sociol. 78, 1360-1380.
53. Green, D. G., Newth, D., and Kirley, M. G. (2000). Connectivity and catastrophe-towards a general theory of evolution, in Artificial Life VII: Proceedings of the Seventh International Conference, 153-161.
54. Griffin, A. (1993). Metrics for measuring product development cycle time. J. Prod. Innov. Manag. 10, 112-125.
55. Guidetti, R., and Jönsson, K. I. (2002). Long-term anhydrobiotic survival in semi-terrestrial micrometazoans. J. Zool. 257, 181-187.
56. Guo, B., Styles, C. A., Feng, Q., and Fink, G. R. (2000). A Saccharomyces gene family involved in invasive growth, cell-cell adhesion, and mating. Proc. Natl. Acad. Sci. U.S.A. 97, 12158-12163.
57. Hamrick, J., and Godt, M. (1996). Effects of life history traits on genetic diversity in plant species. Philos. Trans. R. Soc. Lond. B Biol. Sci. 351, 1291-1298.
58. Harding, A., and Hancock, J. F. (2008). Ras nanoclusters: combining digital and analog signaling. Cell Cycle 7, 127-134.
59. Hayden, E. J., Ferrada, E., and Wagner, A. (2011). Cryptic genetic variation promotes rapid evolutionary adaptation in an RNA enzyme. Nature 474, 92-97.
60. Heylighen, F., and Joslyn, C. (2001). Cybernetics and second order cybernetics. Encyclopedia Phys. Sci. Technol. 4, 155-170.
61. Holling, C. S. (2001). Understanding the complexity of economic, ecological, and social systems. Ecosystems 4, 390-405.
62. Huang, P. H., Mukasa, A., Bonavia, R., Flynn, R. A., Brewer, Z. E., Cavenee, W. K., Furnari, F. B., and White, F. M. (2007). Quantitative analysis of EGFRvIII cellular signaling networks reveals a combinatorial therapeutic strategy for glioblastoma. Proc. Natl. Acad. Sci. 104, 12867.
63. Ingolia, N. T. (2004). Topology and robustness in the Drosophila segment polarity network. PLoS Biol. 2, e123. doi:10.1371/journal.pbio.0020123
64. Isalan, M., Lemerle, C., Michalodimitrakis, K., Horn, C., Beltrao, P., Raineri, E., Garriga-Canut, M., and Serrano, L. (2008). Evolvability and hierarchy in rewired bacterial gene networks. Nature 452, 840-845.
65. Jablonka, E., Oborny, B., Molnár, I., Kisdi, E., Hofbauer, J., and Czárán, T. (1995). The adaptive advantage of phenotypic memory in changing environments. Philos. Trans. R. Soc. Lond. B Biol. Sci. 350, 133-141.
66. Jahnke, S., Memmesheimer, R. M., and Timme, M. (2009). Howchaotic is the balanced state Front. Comput. Neurosci. 3:13. doi:10.3389/neuro.10.013.2009
67. Jeong, H., Mason, S. P., Barabási, A. L., and Oltvai, Z. N. (2001). Lethality and centrality in protein networks. Nature 411, 41-42.
68. Jeong, H., Tombor, B., Albert, R., Oltvai, Z. N., and Barabási, A. L. (2000). The large-scale organization of metabolic networks. Nature 407, 651-654.
69. Jin, Y., and Meng, Y. (2011). Morphogenetic robotics: an emerging new field in developmental robotics. IEEE Trans. Syst. Man Cybern. C Appl. Rev. 41,145-160.
70. Jönsson, K. I., Rabbow, E., Schill, R. O., Harms-Ringdahl, M., and Rettberg, P. (2008). Tardigrades survive exposure to space in low Earth orbit. Curr. Biol. 18,R729-R731.
71. Kacser, H., and Burns, J. A. (1981). The molecular basis of dominance. Genetics 97, 639.
72. Kacser, H., and Burns, J. A. (1995). The control of flux. Biochem. Soc. Trans. 23, 341-366.
73. Kauffman, S. A. (1969). Metabolic stability and epigenesis in randomly constructed genetic nets. J. Theor. Biol. 22,437-467.
74. Kauffman, S. A. (1990). Requirements for evolvability in complex systems: orderly components and frozen dynamics. Physica D 42, 135-152.
75. Kauffman, S. A. (1993). The Origins of Order: Self-Organization and Selection in Evolution. Oxford University Press.
76. Kerkstra, S., and Scha, I. R. (2008). Evolution and the Genotype-Phenotype Map. Masters thesis, University of Amsterdam.
77. Kirschner, M., and Gerhart, J. (1998). Evolvability. Proc. Natl. Acad. Sci. U.S.A. 95, 8420-8427.
78. Kitami, T., and Nadeau, J. H. (2002). Biochemical networking contributes more to genetic buffering in human and mouse metabolic pathways than does gene duplication. Nat. Genet. 32, 191-194.
79. Kitano, H. (2002). Computational systems biology. Nature 420, 206-210.
80. Kitano, H. (2004a). Cancer as a robust system: implications for anti-cancer therapy. Nat. Rev. Cancer 4, 227-235.
81. Kitano, H. (2004b). Biological robustness. Nat. Rev. Genet. 5, 826-837.
82. Kitano, H. (2007). Towards a theory of biological robustness. Mol. Syst. Biol. 3, 1-7.
83. Kitano, H., and Oda, K. (2006). Robustness trade-offs and host-microbial symbiosis in the immune system. Mol. Syst. Biol. 2,2006.0022.
84. Kondoh, M. (2003). Foraging adaptation and the relationship between food-web complexity and stability. Science 299, 1388.
85. Kondoh, M. (2007). Anti-predator defence and the complexity-stability relationship of food webs. Proc. Biol. Sci. 274, 1617.
86. Kupiec, J. J. (1997). A Darwinian theory for the origin of cellular differentiation. Mol. Gen. Genet. 255, 201-208.
87. Kurakin, A. (2009). Scale-free flow of life: on the biology, economics, and physics of the cell. Theor. Biol. Med. Model. 6.
88. Laland, K., and Sterelny, K. (2006). Perspective: seven reasons (not) to neglect niche construction. Evolution 1751-1762.
89. Lehner, B. (2010). Genes confer similar robustness to environmental, stochastic, and genetic perturbations in yeast. PLoS ONE 5, e9035. doi:10.1371/journal.pone.0009035
90. Levchenko, A., and Iglesias, P. (2002). Models of eukaryotic gradient sensing: application to chemotaxis of amoebae and neutrophils. Biophys. J. 82, 50-63.
91. Levin, S., and Lubchenco, J. (2008). Resilience, robustness, and marine ecosystem-based management. Bioscience 58,27-32.
92. Li, F., Long, T., Lu, Y., Ouyang, Q., and Tang, C. (2004). The yeast cell-cycle network is robustly designed. Proc. Natl. Acad. Sci. U.S.A. 101, 4781-4786.
93. Lynch, M. (2007). The frailty of adaptive hypotheses for the origins of organismal complexity. Proc. Natl. Acad. Sci. U.S.A. 104, 8597.
94. Ma, H. W., and Zeng, A. P. (2003). The connectivity structure, giant strong component and centrality of metabolic networks. Bioinformatics 19, 1423-1430.
95. Martin, O., and Wagner, A. (2008). Multifunctionality and robustness trade-offs in model genetic circuits. Biophys. J. 94, 2927-2937.
96. McBride, R. C., Ogbunugafor, C. B., and Turner, P. E. (2008). Robustness promotes evolvability of thermotolerance in an RNA virus. BMC Evol. Biol. 8, 231. doi:10.1186/1471-2148-8-231
97. McCann, K., Hastings, A., and Huxel, G. R. (1998). Weak trophic interactions and the balance of nature. Nature 395, 794-798.
98. McCune, J. M. (2001). The dynamics of CD4+ T-cell depletion in HIV disease. Nature AW, 974-979.
99. Meiklejohn, C. D., and Hartl, D. L. (2002). A single mode ofcanalization. Trends Ecol. Evol. (Amst.) 17,468-473.
100. Mendao, M., Timmis, J., Andrews, P. S., and Davies, M. (2007). The immune system in pieces: computational lessons from degeneracy in the immune system, in IEEE Symposium on Foundations of Computational Intelligence, 2007, 394-400.
101. Meng, Y., Zhang, Y., and Jin, Y (2011). Autonomous self-reconfiguration of modular robots by evolving a hierarchical mechanochemical model. IEEE Comput. Intell. Mag. 6, 43-54.
102. Millson, M. R., Raj, S. P., and Wilemon, D. (1992). A survey of major approaches for accelerating new product development. J. Prod. Innov. Manag. 9, 53-69.
103. Morohashi, M., Winn, A. E., Borisuk, M. T., Bolouri, H., Doyle, J., and Kitano, H. (2002). Robustness as a measure of plausibility in models of biochemical networks. J. Theor. Biol. 216, 19-30.
104. Newman, S. A. (1994). Generic physical mechanisms of tissue morphogenesis: a common basis for development and evolution. J. Evol. Biol. 7, 467-488.
105. Odling-Smee, F., Laland, K. N., and Feldman, M. W (1996). Niche construction. Am. Nat. 147, 641-648.
106. Ozaki, K., and Leonard, W. J. (2002). Cytokine and cytokine receptor pleiotropy and redundancy. J. Biol. Chem. 277,29355.
107. Page, A. L. (1993). Assessing new product development practices and performance: establishing crucial norms. J. Prod. Innov. Manag. 10, 273-290.
108. Pastor-Satorras, R., Smith, E., and Solé, R. V. (2003). Evolving protein interaction networks through gene duplication.J. Theor. Biol. 222, 199-210.
109. Pfennig, D. W., Wund, M. A., Snell-Rood, E. C., Cruickshank, T., Schlichting, C. D., and Moczek, A. P. (2010). Phenotypic plasticity's impacts on diversification and speciation. Trends Ecol. Evol. (Amst.) 25, 459-467.
110. Randles, M., Lamb, D., Odat, E., and Taleb-Bendiab, A. (2010). Distributed redundancy and robustness in complex systems. J. Comput. Syst. Sci. 77, 293-304.
111. Raup, D. M. (1992). Extinction: Bad genes or Bad Luck? WW Norton & Company.
112. Ravasz, E., Somera, A. L., Mongru, D. A., Oltvai, Z. N., and Barabási, A. L. (2002). Hierarchical organization of modularity in metabolic networks. Science 297,1551-1555.
113. Rutherford, S. L. (2000). From genotype to phenotype: buffering mechanisms and the storage of genetic information. Bioessays 22, 1095-1105.
114. Rutherford, S. L. (2003). Between genotype and phenotype: protein chaperones and evolvability. Nat. Rev. Genet. 4, 263.
115. Rutherford, S. L., and Lindquist, S. (1998). Hsp90 as a capacitor for morphological evolution. Nature 336-342.
116. Sauer, U., Canonaco, F., Heri, S., Perrenoud, A., and Fischer, E. (2004). The soluble and membrane-bound transhydrogenases UdhA and PntAB have divergent functions in NADPH metabolism of Escherichia coli. J. Biol. Chem. 279, 6613.
117. Savageau, M. A., Coelho, P. M., Fasani, R. A., Tolla, D. A., and Salvador, A. (2009). Phenotypes and tolerances in the design space of biochemical systems. Proc. Natl Acad. Sci. U.S.A. 106, 6435.
118. Scharloo, W. (1991). Canalization: genetic and developmental aspects. Annu. Rev. Ecol. Syst. 65-93.
119. Seki,K., and Toyoshima, M. (1998). Preserving tardigrades under pressure. Nature 395, 853-854.
120. Shinar, G., and Feinberg, M. (2010). Structural sources of robustness in biochemical reaction networks. Science 327,1389.
121. Siegal, M. L., and Bergman, A. (2002). Waddington's canalization revisited: developmental stability and evolution. Proc. Natl. Acad. Sci. U.S.A. 99, 10528-10532.
122. Smart, A., Amaral, L. A., and Ottino, J. M. (2008). Cascading failure and robustness in metabolic networks. Proc. Natl. Acad. Sci. 105, 13223.
123. Solé, R. V., Pastor-Satorras, R., Smith, E., and Kepler, T. B. (2002). A model of large-scale proteome evolution. Adv. Complex Syst. 5, 43-54.
124. Stelling, J., Klamt, S., Bettenbrock, K., Schuster, S., and Gilles, E. D. (2002). Metabolic network structure determines key aspects offunctionality and regulation. Nature 420, 190-193.
125. Stelling, J., Sauer, U., Szallasi, Z., Doyle, F. J. III, and Doyle, J. (2004a). Robustness of cellular functions. Cell 118,675-685.
126. Stelling, J., Gilles, E. D., and Doyle, F. J. III. (2004b). Robustness properties of circadian clock architectures. Proc. Natl. Acad. Sci. U.S.A. 101, 13210.
127. Stommel, J. M., Kimmelman, A. C., Ying, H., Nabioullin, R., Ponugoti, A. H., Wiedemeyer, R., Stegh, A. H., Bradner, J. E., Ligon, K. L., Brennan, C., Chin, L., and DePinho, R. A. (2007). Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 318, 287.
128. Stromberg, S. P., and Carlson, J. (2006). Robustness and fragility in immunosenescence. PLoS Comput. Biol. 2, e160. doi:10.1371/journal.pcbi.0020160
129. Szollosi, G. J., and Derenyi, I. (2009). Congruent Evolution of Genetic and Environmental Robustness in Micro-RNA. Mol. Biol. Evol. 26, 867.
130. Tanaka, R. (2005). Scale-rich metabolic networks. Phys. Rev. Lett. 94, 168101-168105.
131. Tian, T., Olson, S., Whitacre, J. M., and Harding, A. (2011). The origins of cancer robustness and evolvability. Integr. Biol. (Camb.) 3, 17-30.
132. Tieri, P., Grignolio, A., Zaikin, A., Mishto, M., Remondini, D., Castellani, G. C.,and Franceschi, C. (2010). Network, degeneracy and bow tie integrating paradigms and architectures to grasp the complexity of the immune system. Theor. Biol. Med. Model. 7, 32.
133. Tononi, G., Sporns, O., and Edelman, G. M. (1999). Measures of degeneracy and redundancy in biological networks. Proc. Natl. Acad. Sci. U.S.A. 96,3257-3262.
134. Uller, T. (2008). Developmental plasticity and the evolution of parental effects. Trends Ecol. Evol. (Amst.) 23, 432-438.
135. von Dassow, G., Meir, E., Munro, E. M., and Odell, G. M. (2000). The segment polarity network is a robust developmental module. Nature 406, 188-192.
136. Waddington, C.H. (1942). Canalization of development and the inheritance of acquired characters. Nature 150, 563.
137. Waddington, C. H. (1953). Genetic assimilation of an acquired character. Evolution 7, 118-126.
138. Wagner, A. (2005). Distributed robustness versus redundancy as causes of mutational robustness. Bioessays 27, 176-188.
139. Wagner, A. (2008). Robustness and evolvability: a paradox resolved. Proc. R. Soc. Lond. B Biol. Sci. 275, 91-100.
140. Waldner, J. B. (2008). Nanocomputers and Swarm Intelligence. Wiley-ISTE.
141. Wall, M. E., Hlavacek, W S., and Savageau, M. A. (2004). Design of gene circuits: lessons from bacteria. Nat. Rev. Genet. 5, 34-42.
142. Walter, C. (2005). Kryder's law. Sci. Am. 293,32.
143. West-Eberhard, M. (2005). Developmental plasticity and the origin of species differences. Proc. Natl. Acad. Sci. U.S.A. 102, 6543.
144. West-Eberhard, M. J. (2003). Developmental Plasticity and Evolution. Oxford University Press.
145. Whitacre, J. M. (2010). Degeneracy: a link between evolvability, robustness and complexity in biological systems. Theor. Biol. Med. Model. 7.
146. Whitacre, J. M., and Bender, A. (2010a). Degeneracy: a design principle for achieving robustness and evolvability.J. Theor. Biol. 263, 143-153.
147. Whitacre, J. M., and Bender, A. (2010b). Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems. Theor. Biol. Med. Model. 7.
148. Whitacre, J. M., and Bender, A. (in press). Pervasive flexibility in living technologies through degeneracy based design. Artif. Life.
149. Whitacre, J. M., Lin, J., and Harding, A. (2012). T cell adaptiveimmunity proceeds through environment-induced daptation from the exposure of cryptic genetic variation. Front. Genet. 3:5. doi:10.3389/fgene.2012.00005
150. Whitacre, J. M., Rohlfshagen, P., Bender, A., and Yao, X. (in press). Evolutionary mechanics: new engineering principles for the emergence of flexibility in a dynamic and uncertain world. Nat. Comp.
151. Whitacre, J. M., Rohlfshagen, P., Yao, X., and Bender, A. (2010). The role of degenerate robustness in the evolvability of multi-agent systems in dynamic environments, in PPSN XI, Krakow, 284-293.
152. Wilhelm, T., Behre, J., and Schuster, S. (2004). Analysis of structural robustness of metabolic networks. Syst. Biol. (Stevenage) 1, 114-120.
153. Yi, T. M., Huang, Y., Simon, M. I., and Doyle, J. (2000). Robust perfect adaptation in bacterial chemo-taxis through integral feedback control. Proc. Natl. Acad. Sci. U.S.A. 97, 4649.