Inter individual variability in neuronal expression of heat shock protein genes predicts stress survival inCaenorhabditis elegans

Abstract

Despite being isogenic and grown under controlled conditions, C. elegans populations exhibit widespread inter-individual variability in many traits, making it an ideal model organism to investigate non-genetic influences on phenotypic diversity. Our particular interest is to study the consequences of inter-individual variability in genes encoding heat shock proteins, which are expressed at low levels under non-stimulated conditions. To robustly quantify inter-individual gene expression, we developed a novel pipeline that combines a highly efficient cDNA extraction method with a high-throughput qPCR nanofluidics technology with a bespoke computational analysis. We validated our approach by benchmarking against in vivo reporters. We also screened among hundreds of stress inducible genes, and identified a regulon formed by transcripts belonging to the inducible heat shock protein family. We demonstrate, using a bipartite in vivo fluorescent reporter, that the inter-individual variability in the stress regulon stems mostly from anterior neurons. Our studies demonstrate for the first time that, under physiological and unstimulated conditions, the variable expression of neural stress responses has cross-tissue consequences for fitness at the individual worm level, suggesting an adaptive role under variable environmental conditions.