Frank, S. A. 2023. Disease from opposing forces in regulatory control. Evolution, Medicine, and Public Health. 11:348-352.
Danger requires a strong rapid response. Speedy triggers are prone to false signals. False alarms can be costly, requiring strong negative regulators to oppose the initial triggers. Strongly opposed forces can easily be perturbed, leading to imbalance and disease. For example, immunity and fear response balance strong rapid triggers against widespread slow negative regulators. Diseases of immunity and behavior arise from imbalance. A different opposition of forces occurs in mammalian growth, which balances strong paternally expressed accelerators against maternally expressed suppressors. Diseases of overgrowth or undergrowth arise from imbalance. Other examples of opposing forces and disease include control of dopamine expression and male versus female favored traits.