Correlated stabilizing selection shapes the topology of gene regulatory networks. 2023

Apolline J R Petit, and Jeremy Guez, and Arnaud Le Rouzic
CNRS, IRD, UMR EGCE, Université Paris-Saclay, 91190 Gif-sur-Yvette, France.

The evolution of gene expression is constrained by the topology of gene regulatory networks, as co-expressed genes are likely to have their expressions 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 individual-based simulations, applying a stabilizing correlated fitness function to three genetic architectures: a quantitative genetics (multilinear) model featuring epistasis and pleiotropy, a quantitative genetics model where each genes has an independent mutational structure, and a gene regulatory network model, mimicking the mechanisms of gene expression regulation. Simulations showed that correlated mutational effects evolved in the three genetic architectures as a response to correlated selection, but the response in gene networks was specific. 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 regulation (transcription activation or inhibition). These results concur to the idea that gene network topologies could partly reflect past selection patterns on gene expression.

UI MeSH Term Description Entries
D008957 Models, Genetic Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment. Genetic Models,Genetic Model,Model, Genetic
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D012641 Selection, Genetic Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population. Natural Selection,Genetic Selection,Selection, Natural
D053263 Gene Regulatory Networks Interacting DNA-encoded regulatory subsystems in the GENOME that coordinate input from activator and repressor TRANSCRIPTION FACTORS during development, cell differentiation, or in response to environmental cues. The networks function to ultimately specify expression of particular sets of GENES for specific conditions, times, or locations. Gene Circuits,Gene Modules,Gene Networks,Transcriptional Networks,Gene Module,Circuit, Gene,Circuits, Gene,Gene Circuit,Gene Network,Gene Regulatory Network,Module, Gene,Modules, Gene,Network, Gene,Network, Gene Regulatory,Network, Transcriptional,Networks, Gene,Networks, Gene Regulatory,Networks, Transcriptional,Regulatory Network, Gene,Regulatory Networks, Gene,Transcriptional Network

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