Correlated stabilizing selection shapes the topology of gene regulatory networks

The evolution of gene expression is constrained by the topology of gene regulatory networks, as co-expressed genes are likely to be affected together by mutations. Conversely, co-expression can also be an advantage when genes are under joint selection. Here, we assessed theoretically whether correlated selection (selection for a combination of traits) was able to affect the pattern of correlated gene expressions and the underlying gene regulatory networks. We ran individualbased simulations, applying a stabilizing correlated fitness function to two genetic architectures: a quantitative genetics (multilinear) model featuring epistasis and pleiotropy, and a gene regulatory model, mimicking the mechanisms of gene expression regulation. Simulations showed that correlated mutational effects evolved in both genetic architecture as a response to correlated selection, but the response in gene networks was less precise due to the mechanistic constraints of gene regulation. The intensity of gene co-expression was mostly explained by the regulatory distance between genes (largest correlations being associated to genes directly interacting with each other), and the sign of co-expression was associated with the nature of the regulatory interaction (transcription activation or inhibition). These results concur to the idea that gene network topologies could partly reflects past correlated selection patterns on gene expression.