Stress-Adaptive Survival and Longevity Effects of Tumor Suppressor Mutation: Population Modeling with lgl Gene in Drosophila

Michael Golubovsky, Duke University
Nataly Weisman, Russian Academy of Sciences

Human populations are polymorphic for risk factor mutations predisposing to diseases and cancer. To address how this heterozygosity influences health status in changing environmental/stress conditions we used the model of lgl tumor suppressor (TS) gene in Drosophila. The lgl is the first case of monogenically controlled neoplasia found in animals. Lgl protein is conservative during evolution, mutations of human homologue Hugl discovered in 70% of solid carcinomas. Unexpectedly, our long-term studies showed omnipresence of lgl alleles in geographically distant Drosophila populations. To understand this paradox we compared the survival and longevity profiles of lgl/+ TS-carriers in normal and stress conditions (different omnient temperatures and infection virus susceptibility). TS-carriers had a disadvantage in optimal but appeared adaptive in stress conditions. The TS-dependent stress adaptiveness was maternally mediated. The data obtained are important for better understanding of population spreading of risk factor mutations and their effects on public health in environmental/stress oscillations including climate variability and global catastrophes.