Study on a daf-18/PTEN allele that uncouples distinct phenotypes in daf-2/Insulin/IGF-1 receptor mutant C. elegans

Abstract

Insulin/IGF-1 signaling is one of the well-described and evolutionarily conserved longevity-mediating pathway. The Caenorhabditis elegans daf-2 is a key regulator of lifespan, larval development and resistance to bacterial pathogens. Although many research has been conducted to date, whether the regulation of pleiotropic effects such as development and immunity can be uncoupled at a certain point in IIS pathway has not been addressed yet. In this study, a mutant animal with complete suppression of dauer state which is hibernation-like stage of diapause, and relatively reduced pathogen resistance in daf-2(e1370) mutant background, hereby named as sdli (Suppressor-of-Dauer-but-Less-Immunity), was generated through EMS mutagenesis. Its various physiologic characteristics have been identified. A new mutation on daf-18 gene was reported as the causative of sdli phenotype in daf-2(e1370) mutant animals, whose genotype is daf-2(e1370); daf-18(yh1). It was found out that C105Y change in DAF-18 is the EMS-induced change leading to sdli phenotype. Various life history traits of daf-2(e1370); daf-18(yh1) were examined including lifespan, brood size, and oxidative stress resistance were also examined. Importantly, mutant animal also preserved increased lifespan up to certain level compared to well-known null mutant daf-2(e1370); daf-18(nr2037). This study is important since it is an example of how a specific daf-18 mutation can uncouple certain pleiotropic phenotypes of daf-2(e1370) mutants.