Editing Gene regulatory network (section)

=== Global feature ===
Gene regulatory networks are generally thought to be made up of a few highly connected [[node (graph theory)|node]]s ([[network topology|hubs]]) and many poorly connected nodes nested within a hierarchical regulatory regime. Thus gene regulatory networks approximate a [[Network topology|hierarchical]] [[Scale-free network|scale free network]] topology.<ref name=":0">{{cite journal | vauthors = Barabási AL, Oltvai ZN | title = Network biology: understanding the cell's functional organization | journal = Nature Reviews. Genetics | volume = 5 | issue = 2 | pages = 101–113 | date = February 2004 | pmid = 14735121 | doi = 10.1038/nrg1272 | s2cid = 10950726 }}</ref> This is consistent with the view that most genes have limited [[pleiotropy]] and operate within regulatory [[Modularity (biology)|modules]].<ref>{{cite journal | vauthors = Wagner GP, Zhang J | title = The pleiotropic structure of the genotype-phenotype map: the evolvability of complex organisms | journal = Nature Reviews. Genetics | volume = 12 | issue = 3 | pages = 204–213 | date = March 2011 | pmid = 21331091 | doi = 10.1038/nrg2949 | s2cid = 8612268 }}</ref> This structure is thought to evolve due to the [[preferential attachment]] of [[Gene duplication|duplicated genes]] to more highly connected genes.<ref name=":0" /> Recent work has also shown that natural selection tends to favor networks with sparse connectivity.<ref>{{cite journal | vauthors = Leclerc RD | title = Survival of the sparsest: robust gene networks are parsimonious | journal = Molecular Systems Biology | volume = 4 | issue = 1 | pages = 213 | date = August 2008 | pmid = 18682703 | pmc = 2538912 | doi = 10.1038/msb.2008.52 }}</ref>

There are primarily two ways that networks can evolve, both of which can occur simultaneously. The first is that network topology can be changed by the addition or subtraction of nodes (genes) or parts of the network (modules) may be expressed in different contexts. The'' [[Drosophila]]'' [[Hippo signaling pathway]] provides a good example. The Hippo signaling pathway controls both mitotic growth and post-mitotic cellular differentiation.<ref name=":1">{{cite journal | vauthors = Jukam D, Xie B, Rister J, Terrell D, Charlton-Perkins M, Pistillo D, Gebelein B, Desplan C, Cook T | display-authors = 6 | title = Opposite feedbacks in the Hippo pathway for growth control and neural fate | journal = Science | volume = 342 | issue = 6155 | pages = 1238016 | date = October 2013 | pmid = 23989952 | pmc = 3796000 | doi = 10.1126/science.1238016 }}</ref> Recently it was found that the network the Hippo signaling pathway operates in differs between these two functions which in turn changes the behavior of the Hippo signaling pathway. This suggests that the Hippo signaling pathway operates as a conserved regulatory module that can be used for multiple functions depending on context.<ref name=":1" /> Thus, changing network topology can allow a conserved module to serve multiple functions and alter the final output of the network. The second way networks can evolve is by changing the strength of interactions between nodes, such as how strongly a transcription factor may bind to a [[cis-regulatory element]]. Such variation in strength of network edges has been shown to underlie between species variation in vulva cell fate patterning of ''[[Caenorhabditis]]'' worms.<ref>{{cite journal | vauthors = Hoyos E, Kim K, Milloz J, Barkoulas M, Pénigault JB, Munro E, Félix MA | title = Quantitative variation in autocrine signaling and pathway crosstalk in the Caenorhabditis vulval network | journal = Current Biology | volume = 21 | issue = 7 | pages = 527–538 | date = April 2011 | pmid = 21458263 | pmc = 3084603 | doi = 10.1016/j.cub.2011.02.040 | bibcode = 2011CBio...21..527H }}</ref>