hsp-16.2 chaperone biomarkers track physiological states of proteome dosage

ABSTRACT Phenotypic expression of many traits varies among isogenic individuals in homogeneous environments. Intrinsic variation in the protein chaperone system affects a wide variety of traits in diverse biological systems. In C. elegans , expression of hsp-16.2 chaperone biomarkers predicts the penetrance of mutations and lifespan after heat shock. But the physiological mechanisms by which cells express different amounts of the biomarker were unknown. Here, we used an in vivo microscopy approach to dissect the mechanisms of cell-to-cell variation in hsp-16.2 biomarker expression, focusing on the intestines, which generate most signal. We found both intrinsic noise and signaling noise are low. The major axis of cell-to-cell variation in gene expression is composed of general differences in protein dosage. Thus, hsp-16.2 biomarkers reveal states of high or low effective dosages for many genes. It is possible that natural variation in protein dosage or chaperone activity may account for missing heritability of some traits.