Complex Gene Regulatory Networks – from Structure to Biological Observables: Cell Fate Determination
SUI HUANG, STUART A. KAUFFMAN
"which features [added: of GRNs] are inevitably linked to the very physical processes through which net-works have grown in evolution and which arose due to natural selection because they confer a survival advan- tage [15,77,78,93,203]? Often this question is taken for granted and an all-mighty selection process is assumed that can produce any structure as long as it contributes suf- ficiently to fitness. This however, would require that dur- ing natural selection the random, mutation-driven reshuf- fling of nodes and connections has no constrains and that Darwinian evolution explores the entire space of possible architectures. Clearly this is not the case: physical con- straints in the rearrangement of DNA (insertions, dele- tions, duplications, conversion, etc) [16,170,187] as well as graph theoretical considerations channel the possibil- ities for how one graph can transform into another."
"it is important to note that one genome in principle encodes exactly one fixed net- work, since the network connections are defined by the specific molecular interactions between the protein struc- ture of TFs and the DNA sequence motif of the cis-regula- tory promoter elements they recognize. Both are encoded by the genomic sequence. The often encountered notion that “networks change during development” and that “ev- ery cell type has its own network” is in this strict formalism incorrect –"