Modeling genome-wide by environment interactions through omnigenic interactome networks.

How genes interact with the environment to shape phenotypic variation and evolution is a fundamental question intriguing to biologists from various fields. Existing linear models built on single genes are inadequate to reveal the complexity of genotype-environment (G-E) interactions. Here, we develop a conceptual model for mechanistically dissecting G-E interplay by integrating previously disconnected theories and methods. Under this integration, evolutionary game theory, developmental modularity theory, and a variable selection method allow us to reconstruct environment-induced, maximally informative, sparse, and casual multilayer genetic networks. We design and conduct two mapping experiments by using a desert-adapted tree species to validate the biological application of the model proposed. The model identifies previously uncharacterized molecular mechanisms that mediate trees' response to saline stress. Our model provides a tool to comprehend the genetic architecture of trait variation and evolution and trace the information flow of each gene toward phenotypes within omnigenic networks.