Natural variation in the irld gene family affects insulin/IGF signaling and starvation resistance

Abstract

Starvation resistance is a fundamental, disease-relevant trait, but the genetic basis of its natural variation is unknown. We developed a synthetic population-sequencing approach to measure starvation resistance for many wild C. elegans strains simultaneously. We identified three quantitative trait loci with variants in 16 insulin/EGF receptor-like domain (irld) family members. We show that four irld genes affect starvation resistance by regulating insulin/IGF signaling. We propose that IRLD proteins bind insulin-like peptides to modify signaling in the sensory nervous system thereby affecting organismal physiology. This work demonstrates efficacy of using population sequencing to dissect a complex trait, identifies irld genes that regulate insulin/IGF signaling, and shows that an expanded gene family modifies a deeply conserved signaling pathway to affect a fitness-proximal trait.