Association between gene expression plasticity and regulatory network topology
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What drives the evolution of gene network topology? During the last decades, many looked into it to find structures responsible for gene expression patterns. Gene expression plasticity for instance has been associated with many network structures, but both theoretical results and empirical observations were often equivocal. Our objective was to decipher the regulatory causes of gene expression plasticity, and more specifically, which structures in regulatory networks were relevant for the sensitivity to environmental factors. We sought the common regulatory structures associated with gene expression plasticity between predictions from an evolutionary simulation model and the global regulatory network from Escherichia coli . The combination of empirical and theoretical approaches and their strikingly similar results confirmed that selection promotes more regulation towards plastic genes and, as a consequence, plastic genes were more often regulated by feedforward loops than non-plastic genes. Selection tends to bias the distribution of regulatory loop motifs towards positive feedforward and diamond loops, but this enrichment in specific structures was the same in plastic and non-plastic genes. The impossibility to predict gene expression plasticity from the network regulatory structure opens interesting questions about the nature of the missing information in current systems biology databases.
Significance statement
Organisms can respond to their environment, and some of their traits are said to be plastic, i.e. dependent on environmental signals. At the individual level, understanding how gene expression varies in response to the environment is of critical importance. Some argued that this sensitivity could be deduced from the structure and motifs of gene regulatory networks, but theoretical and empirical studies could not reach a consensus. Here, we aim at disentangling the relationship between regulatory structure and gene expression plasticity, combining empirical data of Escherichia coli and population evolution modelling. Both approaches agree on a larger amount of regulators for plastic genes compared to non-plastic genes. There were clear signals of selection enriching networks in specific structures, such as feedforward loops, but this selection was independent from gene expression plasticity.
