Biology Reference
In-Depth Information
Chapter 2
Complex Systems Biology of Networks:
The Riddle and the Challenge
Miguel A. Aon
Abstract There is no direct relationship between metabolite, mRNA, protein,
and gene; the expression of a gene is not necessarily correlated with the abun-
dance of the corresponding protein product, and the activity of a protein may
depend on posttranslational modifications, e.g., phosphorylation, redox-modulation/
modification, and acetylation. It is believed that the diverse nature and outcomes of
networks composed of genes, transcripts, proteins, and metabolites remain an
obstacle for tracing the flux from genes to proteins in order to be able to capture
or explain developmental programs or the underlying mechanisms of a disease.
A different approach is needed to address this problem, and accordingly an alter-
native view based on the dynamic integration of three different kinds of networks,
mass-energy, information, and signaling, is proposed and developed in this chapter.
From this perspective, the spatio-temporal expression of mass-energy transforma-
tion and information-carrying networks is modulated by signaling networks
associated with fundamental cellular processes such as cell division, differentiation,
and autophagy. The dynamic network of reaction fluxes (i.e., the fluxome)
represents the ultimate integrative outcome of the whole process. This
approach—which accounts for the basic biological fact that cells and organisms
make themselves—can only be realized by networks connected by overall cyclic
topologies. Thereby, the output of mass-energy/information networks, composed
of proteins, transcriptional factors, metabolites, is at the same time input for
signaling networks which output activates or represses those same networks that
produced them.
( ... ) If the genes are “essentially the same,” what then is it that makes one organism a fly
and another a mouse, a chimp, or a human? The answer, it seems, is to be found in the
structure of gene networks—in the way in which genes are connected to other genes by the
complex regulatory mechanisms that, in their interactions, determine when and where a
particular gene will be expressed. But unlike the sequence of the genome, this regulatory
M.A. Aon ( * )
Division of Cardiology, Johns Hopkins University, Baltimore, MD 21205, USA
e-mail: maon1@jhmi.edu
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