Fig. 5: Working model.

a Genetic experiments from Mendenhall et al. show that interindividual variation in the hsp-16.2 reporter gene arises from differences in insulin signaling and depolarization of the AFD neuron pair¹⁴. Thus, animals with low insulin signaling and high neuronal depolarization would have the highest expression of the hsp-16.2 lifespan/penetrance biomarker and have the longest lifespans, highest penetrance of hypermorphic phenotypes and lowest penetrance of hypomorphic phenotypes. b Diagram of the molecular and physiological differences in cells that underlie global differences in protein dosage. Solid arrows are directly supported by experiments in C. elegans using reporter genes (here in Figs. 3, 4, and Supplementary Fig. 12) and microarrays (previously²⁷). c Three panels showing consequences of different states of protein expression capacity (G). Left panel shows an individual with average G and wild-type phenotypes. Middle panel shows an individual with low G and penetrance of a hypormorphic phenotype for the allele of Gene C. Right panel shows an individual with high G and penetrance of a hypermorphic phenotype for the allele of Gene B.