A Cross-Species Homeostatic Window of Gene Expression Noise: From Coral to Mammalian Cells

A fundamental challenge in genetic engineering and synthetic biology is that while we can precisely tune gene expression levels, we lack a universal metric for determining "how much is enough". Overexpression causes cytotoxicity, underexpression fails to produce a phenotype, and the optimal level is typically found through trial-and-error. Here we analyzed 12 publicly available transcriptome datasets from coral, sea anemone, yeast, Arabidopsis, and mouse under heat stress. We propose that the coefficient of variation (CV) of core stress-responsive genes has a cross-species homeostatic window of 0.05-0.30. Within this window, cells and organisms exhibit the highest stress tolerance and functional robustness. CV < 0.05 indicates transcriptional rigidity (insufficient response), while CV > 0.30 indicates chaotic overload (cytotoxicity). The window is consistent across species and conditions, and the CV converges toward the lower part of the window (0.12-0.18) after heat acclimation. This homeostatic window hypothesis provides a quantitative, species-independent benchmark for gene expression tuning, with potential applications in synthetic biology, gene therapy, and ecological engineering.