Robustness and Evolvability of the Human Signaling Network

Cited 21 time in webofscience Cited 0 time in scopus
  • Hit : 267
  • Download : 0
Biological systems are known to be both robust and evolvable to internal and external perturbations, but what causes these apparently contradictory properties? We used Boolean network modeling and attractor landscape analysis to investigate the evolvability and robustness of the human signaling network. Our results show that the human signaling network can be divided into an evolvable core where perturbations change the attractor landscape in state space, and a robust neighbor where perturbations have no effect on the attractor landscape. Using chemical inhibition and overexpression of nodes, we validated that perturbations affect the evolvable core more strongly than the robust neighbor. We also found that the evolvable core has a distinct network structure, which is enriched in feedback loops, and features a higher degree of scale-freeness and longer path lengths connecting the nodes. In addition, the genes with high evolvability scores are associated with evolvability-related properties such as rapid evolvability, low species broadness, and immunity whereas the genes with high robustness scores are associated with robustness-related properties such as slow evolvability, high species broadness, and oncogenes. Intriguingly, US Food and Drug Administration-approved drug targets have high evolvability scores whereas experimental drug targets have high robustness scores.
Publisher
PUBLIC LIBRARY SCIENCE
Issue Date
2014-07
Language
English
Article Type
Article
Keywords

EVOLUTIONARY DESIGN PRINCIPLES; GENETIC REGULATORY NETWORKS; BIOLOGICAL NETWORKS; RAPID EVOLUTION; BOOLEAN NETWORK; FEEDBACK LOOPS; MODELS; PATHWAY; TRANSDUCTION; ADAPTATION

Citation

PLOS COMPUTATIONAL BIOLOGY, v.10, no.7

ISSN
1553-7358
DOI
10.1371/journal.pcbi.1003763
URI
http://hdl.handle.net/10203/192649
Appears in Collection
BiS-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 21 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0