Crosstalk and the evolvability of intracellular communication

Michael A. Rowland, Joseph M. Greenbaum and Eric J. Deeds ()
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Michael A. Rowland: Environmental Laboratory, US Army Engineer Research and Development Center, 3909 Halls Ferry Road, Vicksburg, Mississippi 39180, USA
Joseph M. Greenbaum: Center for Computational Biology, University of Kansas, 2030 Becker Dr Lawrence, Kansas 66047, USA
Eric J. Deeds: Center for Computational Biology, University of Kansas, 2030 Becker Dr Lawrence, Kansas 66047, USA

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms16009

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