The nematode Caenorhabditis elegans responds to overcrowding and scarcity of food by arresting development as a dauer larva, a nonfeeding, long-lived, stress-resistant, alternative third-larval stage. Previous work has shown that mutations in the genes
daf-2 (encoding a member of the insulin receptor family) and
age-1 (encoding a PI 3-kinase) result in constitutive formation of dauer larvae (Daf-c), increased adult longevity (Age), and increased intrinsic thermotolerance (Itt). Some
daf-2 mutants have additional developmental, behavioral, and reproductive defects. We have characterized in detail 15 temperature-sensitive and 1 nonconditional
daf-2 allele to investigate the extent of
daf-2 mutant defects and to examine whether specific mutant traits correlate with each other. The greatest longevity seen in
daf-2 mutant adults was approximately three times that of wild type. The temperature-sensitive
daf-2 mutants fell into two overlapping classes, including eight class 1 mutants, which are Daf-c, Age, and Itt, and exhibit low levels of L1 arrest at 25.5 degrees. Seven class 2 mutants also exhibit the class 1 defects as well as some or all of the following: reduced adult motility, abnormal adult body and gonad morphology, high levels of embryonic and L1 arrest, production of progeny late in life, and reduced brood size. The strengths of the Daf-c, Age, and Itt phenotypes largely correlated with each other but not with the strength of class 2-specific defects. This suggests that the DAF-2 receptor is bifunctional. Examination of the null phenotype revealed a maternally rescued egg, L1 lethal component, and a nonconditional Daf-c component. With respect to the Daf-c phenotype, the dauer-defective (Daf-d) mutation
daf-12(
m20) was epistatic to
daf-2 class 1 alleles but not the severe class 2 alleles tested. All
daf-2 mutant defects were suppressed by the daf-d mutation
daf-16(
m26). Our findings suggest a new model for
daf-2,
age-1,
daf-12, and
daf-16 interactions.