Crosstalk and the evolvability of intracellular communication

• Published in: Nature communications Vol. 8; no. 1; p. 16009
• Main Authors: Rowland, Michael A., Greenbaum, Joseph M., Deeds, Eric J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10-07-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/553/2703; 631/553/2712; 96/95; Apoptosis; Boolean; Cellular communication; Communication; Crosstalk; Cytokines; Evolution; Evolution, Molecular; Gene expression; Human tissues; Humanities and Social Sciences; Humans; Hypotheses; Intracellular signalling; Kinases; Models, Genetic; multidisciplinary; Proteins; Receptor Cross-Talk; Science; Science (multidisciplinary); Signal transduction; Signal Transduction - genetics; Tissues
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms16009

Metazoan signalling networks are complex, with extensive crosstalk between pathways. It is unclear what pressures drove the evolution of this architecture. We explore the hypothesis that crosstalk allows different cell types, each expressing a specific subset of signalling proteins, to activate different outputs when faced with the same inputs, responding differently to the same environment. We find that the pressure to generate diversity leads to the evolution of networks with extensive crosstalk. Using available data, we find that human tissues exhibit higher levels of diversity between cell types than networks with random expression patterns or networks with no crosstalk. We also find that crosstalk and differential expression can influence drug activity: no protein has the same impact on two tissues when inhibited. In addition to providing a possible explanation for the evolution of crosstalk, our work indicates that consideration of cellular context will likely be crucial for targeting signalling networks.
The evolutionary rationale behind the extensive crosstalk between Metazoan signalling pathways remains elusive. Here the authors provide evidence that crosstalk in the human signalling network evolves as a means to allow efficient diversification of cellular responses to the same signals between different cell types.