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Genetics. Sep 1998; 150(1): 129–155.
PMCID: PMC1460297

Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans.

Abstract

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.

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Selected References

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  • Gottlieb S, Ruvkun G. daf-2, daf-16 and daf-23: genetically interacting genes controlling Dauer formation in Caenorhabditis elegans. Genetics. 1994 May;137(1):107–120. [PMC free article] [PubMed]
  • Hodgkin J. Male Phenotypes and Mating Efficiency in CAENORHABDITIS ELEGANS. Genetics. 1983 Jan;103(1):43–64. [PMC free article] [PubMed]
  • Johnson TE, Wood WB. Genetic analysis of life-span in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6603–6607. [PMC free article] [PubMed]
  • Johnson TE, Mitchell DH, Kline S, Kemal R, Foy J. Arresting development arrests aging in the nematode Caenorhabditis elegans. Mech Ageing Dev. 1984 Nov;28(1):23–40. [PubMed]
  • Kapeller R, Cantley LC. Phosphatidylinositol 3-kinase. Bioessays. 1994 Aug;16(8):565–576. [PubMed]
  • Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R. A C. elegans mutant that lives twice as long as wild type. Nature. 1993 Dec 2;366(6454):461–464. [PubMed]
  • Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science. 1997 Aug 15;277(5328):942–946. [PubMed]
  • Klass M, Hirsh D. Non-ageing developmental variant of Caenorhabditis elegans. Nature. 1976 Apr 8;260(5551):523–525. [PubMed]
  • Larsen PL. Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8905–8909. [PMC free article] [PubMed]
  • Larsen PL, Albert PS, Riddle DL. Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics. 1995 Apr;139(4):1567–1583. [PMC free article] [PubMed]
  • Lin K, Dorman JB, Rodan A, Kenyon C. daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science. 1997 Nov 14;278(5341):1319–1322. [PubMed]
  • Lithgow GJ, White TM, Hinerfeld DA, Johnson TE. Thermotolerance of a long-lived mutant of Caenorhabditis elegans. J Gerontol. 1994 Nov;49(6):B270–B276. [PubMed]
  • Lithgow GJ, White TM, Melov S, Johnson TE. Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7540–7544. [PMC free article] [PubMed]
  • Malone EA, Thomas JH. A screen for nonconditional dauer-constitutive mutations in Caenorhabditis elegans. Genetics. 1994 Mar;136(3):879–886. [PMC free article] [PubMed]
  • Malone EA, Inoue T, Thomas JH. Genetic analysis of the roles of daf-28 and age-1 in regulating Caenorhabditis elegans dauer formation. Genetics. 1996 Jul;143(3):1193–1205. [PMC free article] [PubMed]
  • Morris JZ, Tissenbaum HA, Ruvkun G. A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature. 1996 Aug 8;382(6591):536–539. [PubMed]
  • Antebi A, Culotti JG, Hedgecock EM. daf-12 regulates developmental age and the dauer alternative in Caenorhabditis elegans. Development. 1998 Apr;125(7):1191–1205. [PubMed]
  • Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, Ruvkun G. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature. 1997 Oct 30;389(6654):994–999. [PubMed]
  • Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974 May;77(1):71–94. [PMC free article] [PubMed]
  • Cassada RC, Russell RL. The dauerlarva, a post-embryonic developmental variant of the nematode Caenorhabditis elegans. Dev Biol. 1975 Oct;46(2):326–342. [PubMed]
  • Chisholm AD, Horvitz HR. Patterning of the Caenorhabditis elegans head region by the Pax-6 family member vab-3. Nature. 1995 Sep 7;377(6544):52–55. [PubMed]
  • Partridge L, Harvey PH. The ecological context of life history evolution. Science. 1988 Sep 16;241(4872):1449–1455. [PubMed]
  • Dorman JB, Albinder B, Shroyer T, Kenyon C. The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans. Genetics. 1995 Dec;141(4):1399–1406. [PMC free article] [PubMed]
  • Friedman DB, Johnson TE. A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics. 1988 Jan;118(1):75–86. [PMC free article] [PubMed]
  • Gems D, Riddle DL. Longevity in Caenorhabditis elegans reduced by mating but not gamete production. Nature. 1996 Feb 22;379(6567):723–725. [PubMed]
  • Golden JW, Riddle DL. The Caenorhabditis elegans dauer larva: developmental effects of pheromone, food, and temperature. Dev Biol. 1984 Apr;102(2):368–378. [PubMed]
  • Riddle DL, Swanson MM, Albert PS. Interacting genes in nematode dauer larva formation. Nature. 1981 Apr 23;290(5808):668–671. [PubMed]
  • Sohal RS, Buchan PB. Relationship between physical activity and life span in the adult housefly, Musca domestica. Exp Gerontol. 1981;16(2):157–162. [PubMed]
  • Wadsworth WG, Riddle DL. Developmental regulation of energy metabolism in Caenorhabditis elegans. Dev Biol. 1989 Mar;132(1):167–173. [PubMed]
  • Ward S, Carrel JS. Fertilization and sperm competition in the nematode Caenorhabditis elegans. Dev Biol. 1979 Dec;73(2):304–321. [PubMed]
  • Williams BD, Schrank B, Huynh C, Shownkeen R, Waterston RH. A genetic mapping system in Caenorhabditis elegans based on polymorphic sequence-tagged sites. Genetics. 1992 Jul;131(3):609–624. [PMC free article] [PubMed]
  • Trent C, Tsuing N, Horvitz HR. Egg-laying defective mutants of the nematode Caenorhabditis elegans. Genetics. 1983 Aug;104(4):619–647. [PMC free article] [PubMed]
  • Zhang Y, Emmons SW. Specification of sense-organ identity by a Caenorhabditis elegans Pax-6 homologue. Nature. 1995 Sep 7;377(6544):55–59. [PubMed]
  • Trout WE, Kaplan WD. A relation between longevity, metabolic rate, and activity in shaker mutants of Drosophila melanogaster. Exp Gerontol. 1970 Apr;5(1):83–92. [PubMed]

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