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Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13439-44. Epub 2005 Sep 9.

Eukaryotic cells are dynamically ordered or critical but not chaotic.

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  • 1Institute for Systems Biology, Seattle, WA 98103, USA.


Two important theoretical approaches have been developed to generically characterize the relationship between the structure and function of large genetic networks: the continuous approach, based on reaction-kinetics differential equations, and the Boolean approach, based on difference equations and discrete logical rules. These two approaches do not always coincide in their predictions for the same system. Nonetheless, both of them predict that the highly nonlinear dynamics exhibited by genetic regulatory systems can be characterized into two broad regimes, to wit, an ordered regime where the system is robust against perturbations, and a chaotic regime where the system is extremely sensitive to perturbations. It has been a plausible and long-standing hypothesis that genomic regulatory networks of real cells operate in the ordered regime or at the border between order and chaos. This hypothesis is indirectly supported by the robustness and stability observed in the phenotypic traits of living organisms under genetic perturbations. However, there has been no systematic study to determine whether the gene-expression patterns of real cells are compatible with the dynamically ordered regimes predicted by theoretical models. Using the Boolean approach, here we show what we believe to be the first direct evidence that the underlying genetic network of HeLa cells appears to operate either in the ordered regime or at the border between order and chaos but does not appear to be chaotic.

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