Robustness and evolvability of the human signaling network
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 netw...
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Published in | PLoS computational biology Vol. 10; no. 7; p. e1003763 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
01.07.2014
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors have declared that no competing interests exist. Conceived and designed the experiments: KHC. Performed the experiments: DV AGM. Analyzed the data: JK DV JRK WK KHC. Contributed reagents/materials/analysis tools: JK DV JRK AGM. Wrote the paper: JK DV JRK WK KHC. Performed simulations: JK JRK. |
ISSN: | 1553-7358 1553-734X 1553-7358 |
DOI: | 10.1371/journal.pcbi.1003763 |