Network properties constrain natural selection on gene expression in Caenorhabditis elegans

Gene regulatory networks (GRNs) integrate genetic and environmental signals to coordinate complex phenotypes and evolve through a balance of selection and drift. Using publicly available datasets from Caenorhabditis elegans , we investigated the extent of natural selection on transcript abundance by linking population-scale variation in gene expression to fecundity, a key fitness component. While the expression of most genes covaried only weakly with fitness, which is typical for polygenic traits, we identified seven transcripts under significant directional selection. These included nhr-114 and feh-1, implicating variation in nutrient-sensing and metabolic pathways as impacting fitness. Stronger directional selection on tissue-specific and older genes highlighted the germline and nervous system as focal points of adaptive change. Network position further constrained selection on gene expression; high-connectivity genes faced stronger stabilizing and directional selection, highlighting GRN architecture as a key factor in microevolutionary dynamics. The activity of transcription factors such as zip-3 , which regulates mitochondrial stress responses, emerged as targets of selection, revealing potential links between energy homeostasis and fitness. Our findings demonstrate how GRNs mediate the interplay between selection and drift, shaping microevolutionary trajectories of gene expression and phenotypic diversity.