Topological features of gene regulatory networks predict patterns of natural diversity in environmental response

Molecular interactions affect the evolution of complex traits. For instance, adaptation may be constrained by pleiotropic or epistatic effects, both of which will be reflected in the structure of molecular interaction networks. To date, empirical studies investigating the role of molecular interactions in phenotypic evolution have been idiosyncratic, offering no clear patterns. Here, we investigated the network topology of genes putatively involved in local adaptation to two abiotic stressors--drought and cold--in Arabidopsis thaliana. Our findings suggest that the gene-interaction topologies for both cold and drought stress response are non-random, with genes that show genetic variation in drought response (GxE) being significantly more peripheral and cold response genes being significantly more central than genes not involved in either response. We suggest that the observed topologies reflect different constraints on the genetic pathways involved in the assayed phenotypes. The approach presented here may inform predictive models linking genetic variation in molecular signaling networks with phenotypic variation, specifically traits involved in environmental response.\n\nSignificance StatementOur study focuses on genes whose transcriptional activity exhibits genetic variation in response to the environment, or \"GxE.\" GxE is a widely observed phenomenon of critical importance to understanding the genotype-to-phenotype map, the evolution of natural populations, medical genetics, population response to climate change, and agricultural improvement. We investigated expression GxE in plant responses to two abiotic cues: cold and drought. We found that genes showing genetically variable response to cold stress are centrally located in regulatory networks whereas genes showing genetically variable response to drought stress are peripherally located in regulatory networks. This result suggests that selection is presented with vastly different mutational landscapes for shaping evolutionary or breeding response to these two important climatic factors