Jones et al 2001 T2 lifespan and Dauer, 26 genes Gene list file name: Jones2001.T2_lifespan_Dauer.txt Type of gene identifier: Cosmid name Description: Jones et al 2001 Table2: Expression of Genes Implicated Previousl in Lifespan and Dauer Organism: Caenorhabditis elegans (nematode) Gene list type: Experimental Gene name Source Gene ID All gene names WormBase description WormBase CDS description Proteome description Member of lists (Publications) Other annotations B0240.3 B0240.3 daf-11; B0240.3; 5M200; CE05174; NM_073559; WBGene00000907; WP:CE05174 The daf-11 gene encodes a guanylate cyclase that affects dauer formation, chemotaxis, and axon formation; it is genetically upstream of daf-12 with respect to dauer larvae formation and is expressed in a subset of amphid neurons. guanylate cyclase Jones et al 2001 T2 lifespan and Dauer B0334.8 B0334.8 age-1; daf-23; B0334.8; 2L810; CE23506; NM_064061; WBGene00000090; WP:CE23506 age-1 encodes the C. elegans ortholog of the phosphoinositide 3-kinase (PI3K) p110 catalytic subunit; AGE-1, supplied maternally and embryonically, is a central component of the C. elegans insulin-like signaling pathway, lying downstream of the DAF-2/insulin receptor and upstream of both the PDK-1 and AKT-1/AKT-2 kinases and the DAF-16 forkhead type transcription factor, whose negative regulation is the key output of the insulin signaling pathway; in accordance with its role in insulin signaling, AGE-1 activity is required for regulation of metabolism, life span, dauer formation, stress resistance, fertility, and embryonic development; although the age-1 expression pattern has not yet been reported, ectopic expression studies indicate that pan-neuronal age-1 expression is sufficient to rescue life-span defects, while neuronal, intestinal, or muscle expression can partially rescue dauer formation, and neuronal or muscle expression can rescue metabolic defects. phosphatidylinositol 3-kinase Jones et al 2001 T2 lifespan and Dauer, McCarroll et al 2004 SFig1-4 conserved w/ Drosoph, Reinke et al 2004, list of genes in cluster F, Reinke et al 2004, fem1 enriched genes, Reinke et al 2004, list of genes in cluster order, Reinke et al 2004, oogenesis enriched genes, Reinke et al 2004, wt vs glp-4 enriched genes, ViswanathanM et al 2005 S2 sir-2.1 regulated B0412.2 B0412.2 daf-7; B0412.2; 3B431; CE01758; NM_064864; WBGene00000903; WP:CE01758 daf-7 encodes a member of the transforming growth factor beta superfamily that affects dauer larvae formation in a TGF-beta-mediated pathway and also affects egg laying; expressed in the ASI neurons. transforming growth factor beta proteins Jones et al 2001 T2 lifespan and Dauer, Reinke et al 2004, list of genes in cluster A, Reinke et al 2004, list of genes in cluster order C08A9.1 C08A9.1 sod-3; C08A9.1; CE08002; MnSOD; NM_078363; WBGene00004932; WP:CE08002; XR707 sod-3 encodes a iron/manganese superoxide dismutase, predicted to be mitochondrial, that might defend against oxidative stress and promote normal lifespan; sod-3 mRNA levels are diminished by mutation of daf-16, and heterologously expressed SOD-3 in E. coli protects against methyl viologen-induced oxidative stress. superoxide dismutase Jones et al 2001 T2 lifespan and Dauer, Lund et al 2002 Fig4 Mount 15, McElwee et al 2003 T1 targets of daf-16, McElwee et al 2003 Fig4 daf-16 target lifspan, Murphy et al 2003 Fig2 Class1 elongate lifespan, Reinke et al 2004, fem1 enriched genes, Reinke et al 2004, mixed oogenesis soma, ViswanathanM et al 2005 S2 daf-16 Resveratrol, ViswanathanM et al 2005 S2 sir-2.1 regulated, Wang et al 2003 S6 removed genes of contamination C08H9.5 C08H9.5 old-1; tkr-1; C08H9.5; 2K154; CE02991; NM_063729; WBGene00003862; WP:CE02991 tyrosine-protein kinase (KIN15/KIN16 subfamily) Jones et al 2001 T2 lifespan and Dauer, ViswanathanM et al 2005 S2 sir-2.1 regulated C11E4.1 C11E4.1 C11E4.1; CE31410; WBGene00007516; WP:CE31410; XK203 glutathione peroxidase Jones et al 2001 T2 lifespan and Dauer, Wang et al 2003 S3 genes pass one-way ANOVA, Wang et al 2003 S4 Dauer Enriched, Wang et al 2003 S4 genes pass two-wayANOVA P0 C11E4.2 C11E4.2 C11E4.2; CE08102; WBGene00007517; WP:CE08102; XK205 glutathione peroxidase Jones et al 2001 T2 lifespan and Dauer, ViswanathanM et al 2005 S2 sir-2.1 regulated, ViswanathanM et al 2005 S2 daf-16 Resveratrol, Wang et al 2003 S3 genes pass one-way ANOVA, Wang et al 2003 S4 Dauer Enriched, Wang et al 2003 S4 genes pass two-wayANOVA P0 C15F1.7 C15F1.b sod-1; C15F1.7; C15F1.7b.1; C15F1.7b.2; C15F1.B; 2H264; CE20508; CE23550; NM_063030; WBGene00004930; WP:CE20508; WP:CE23550 The sod-1 gene encodes an ortholog of human SOD1 (OMIM:147450), which when mutated leads to amyotrophic lateral sclerosis (OMIM:105400). McCarroll et al 2004 SFig5 conserved w/ yeast, McCarroll et al 2004 SFig1-4 conserved w/ Drosoph, ViswanathanM et al 2005 S2 sir-2.1 regulated F25E2.5 F25E2.5 daf-3; F25E2.5; CE26364; CE28002; CE30963; NM_075760; WBGene00000899; WP:CE26364; WP:CE28002; WP:CE30963; XB438 daf-3 encodes a Smad protein; DAF-3 functions as a transcriptional regulator that is required for formation of the alternative dauer larval stage; DAF-3 activity is antagonized by signaling through the DAF-7/TGF-beta pathway which promotes reproductive growth; in yeast two-hybrid studies, DAF-3 interacts with SMA-3, another Smad protein that does not appear to have a role in dauer formation; a DAF-3::GFP fusion protein is expressed in many tissues that undergo remodeling during dauer development; DAF-3 localizes predominantly to the cytoplasm, but is also found associated with chromosomes in mitotic cells. Jones et al 2001 T2 lifespan and Dauer, ViswanathanM et al 2005 S2 daf-16 Resveratrol F26E4.12 F26E4.12 F26E4.12; 1K359; CE09696; WBGene00009165; WP:CE09696 glutathione peroxidase Jones et al 2001 T2 lifespan and Dauer, McCarroll et al 2004 SFig5 conserved w/ yeast, McCarroll et al 2004 SFig1-4 conserved w/ Drosoph, ViswanathanM et al 2005 S2 sir-2.1 regulated F29C4.1 F29C4.1 daf-1; F29C4.1; 4A889; CE17719; CE31492; WBGene00000897; WP:CE17719; WP:CE31492 daf-1 encodes a TGF-beta type I receptor homolog required, in association with the TGF beta-like type II receptor DAF-4, for the regulation of dauer formation by environmental signals through the ASI chemosensory neuron; DAF-1 is bound by BRA-1 and has an intracellular serine-threonine kinase domain; mutations in daf-1 result in constitutive formation of dauer larvae even in abundant food. protein kinase Jones et al 2001 T2 lifespan and Dauer, McCarroll et al 2004 SFig1-4 conserved w/ Drosoph, Reinke et al 2004, fem1 enriched genes, Reinke et al 2004, mixed oogenesis soma, ViswanathanM et al 2005 S2 sir-2.1 regulated F33H1.1 F33H1.1 daf-19; daf-24; F33H1.1; 2K448; CE17763; CE28019; WBGene00000914; WP:CE17763; WP:CE28019 DNA binding transcription factor Jones et al 2001 T2 lifespan and Dauer, McCarroll et al 2004 SFig5 conserved w/ yeast, McCarroll et al 2004 SFig1-4 conserved w/ Drosoph F55H2.1 F55H2.1 SOD4-1; sod-4; F55H2.1; 3K588; CE25009; NM_066690; WBGene00004933; WP:CE25009 Superoxide dismutase Jones et al 2001 T2 lifespan and Dauer, McCarroll et al 2004 SFig1-4 conserved w/ Drosoph H42K12.1 H42K12.1 pdk-1; H33H01.A; H42K12.1; CE28739; CE28740; WBGene00003965; WP:CE28739; WP:CE28740; XB945 The pdk-1 gene encodes an ortholog of the human 3-phosphoinositide dependent kinase 1 (PDK1; OMIM:605213). Jones et al 2001 T2 lifespan and Dauer, McCarroll et al 2004 SFig1-4 conserved w/ Drosoph, Reinke et al 2004, fem1 enriched genes, Reinke et al 2004, mixed oogenesis soma R03G5.5 R03G5.5 R03G5.5; CE07402; WBGene00019846; WP:CE07402; XI416 glutathione peroxidase Custodia et al 2001 T2 Glut-S-transferase, Jones et al 2001 T2 lifespan and Dauer, ViswanathanM et al 2005 S2 sir-2.1 regulated, Wang et al 2003 S4 Climbing, Wang et al 2003 S3 genes pass one-way ANOVA, Wang et al 2003 S4 genes pass two-wayANOVA P0 R10H10.2 R10H10.2 spe-26; R10H10.2; 4L154; CE06293; NM_069518; WBGene00004972; WP:CE06293 spe-26 encodes a Kelch motif-containing protein similar to the Drosophila proteins kelch and diablo and the Limulus (horseshoe crab) actin-bundling protein scruin; SPE-26 activity is required for several processes including embryogenesis, spermatogenesis, thermotolerance, and regulation of lifespan; SPE-26 mRNA is detected in spermatogonial cells and spermatocytes, but not in spermatids. MIPP repeats Jones et al 2001 T2 lifespan and Dauer, Reinke et al 2004, wt vs glp-4 enriched genes, Reinke et al 2004, list of genes in cluster order, Reinke et al 2004, wt males vs glp4 male enriched , Reinke et al 2004, spermatogenesis enriched genes, Reinke et al 2004, list of genes in cluster D, Reinke et al 2004, fem3 enriched genes, Reinke et al 2004, shared sperm R11A8.4 R11A8.4 sir-2.1; R11A8.4; R11A8.4.1; R11A8.4.2; 4L128; CE06302; NM_069511; WBGene00004800; WP:CE06302 sir-2.1 encodes a homolog of the S. cerevisiae gene SIR2. Yeast regulatory protein SIR2 like Jones et al 2001 T2 lifespan and Dauer, McCarroll et al 2004 SFig5 conserved w/ yeast, McCarroll et al 2004 SFig1-4 conserved w/ Drosoph, Reinke et al 2004, wt herm vs wt male enriched gen, ViswanathanM et al 2005 S2 sir-2.1 regulated, Wang et al 2003 S3 genes pass one-way ANOVA, Wang et al 2003 S4 Dauer Enriched, Wang et al 2003 S4 genes pass two-wayANOVA P0 R13H8.1 R13H8.1 daf-16; daf-17; R13H8.1; R13H8.1e.1; R13H8.1e.2; 1L351; CE28771; CE28772; CE28773; CE33160; CE38722; CE38723; WBGene00000912; WP:CE28771; WP:CE28772; WP:CE28773; WP:CE33160; WP:CE38722; WP:CE38723 daf-16 encodes a transcription factor of the HNF-3/forkhead family (orthologous to mammalian AFX, FKHR, and FKHRL1) that acts in an insulin-mediated pathway to affect dauer formation, and that also affects life span and reproduction; DAF-16 can interact with CBP-1 in vitro, and interacts genetically both with other genes in the insulin signaling and with the nuclear hormone receptor DAF-12; daf-16 is broadly expressed in most if not all cells (though expression in the pharynx and in the somatic gonad differ for the two isoforms); DAF-16 is homologous to human FORKHEAD BOX O1A (FOXO1A), which when mutated leads to rhabdomyosarcoma (OMIM:136533). Jones et al 2001 T2 lifespan and Dauer, McElwee et al 2003 Fig4 daf-16 target lifspan, Wang et al 2003 S4 TransientList, Wang et al 2003 S3 genes pass one-way ANOVA, Wang et al 2003 S4 Dauer Enriched, Wang et al 2003 S4 genes pass two-wayANOVA P0, Wang et al 2003 Fig7 daf-16 T07A9.6 T07A9.6 daf-18; T07A9.6; 4B174; CE26385; NM_067525; WBGene00000913; WP:CE26385 daf-18 encodes a lipid phosphatase homologous to the human PTEN tumor suppresor (OMIM:601728, mutated in Cowden disease and several cancers); DAF-18 negatively regulates insulin-like signaling mediated by DAF-2/IR and AGE-1/PI3K and thus plays a role in metabolism, development, and longevity; based on sequence and genetic analysis, DAF-18 is predicted to dephosphorylate AGE-1-generated PIP3 in order to limit activation of the downstream AKT-1 and AKT-2 kinases that negatively regulate DAF-16. Jones et al 2001 T2 lifespan and Dauer, McCarroll et al 2004 SFig1-4 conserved w/ Drosoph, Reinke et al 2004, fem1 enriched genes, Reinke et al 2004, list of genes in cluster order, Reinke et al 2004, oogenesis enriched genes, Reinke et al 2004, wt vs glp-4 enriched genes, Reinke et al 2004, wt herm vs wt male enriched gen, Reinke et al 2004, list of genes in cluster E, ViswanathanM et al 2005 S2 daf-16 Resveratrol, ViswanathanM et al 2005 S2 sir-2.1 regulated T24H7.1 T24H7.1 phb-2; T24H7.1; 2G543; CE02883; NM_062849; WBGene00004015; WP:CE02883 Prohibitin Jones et al 2001 T2 lifespan and Dauer, McCarroll et al 2004 SFig5 conserved w/ yeast, McCarroll et al 2004 SFig1-4 conserved w/ Drosoph, ViswanathanM et al 2005 S2 sir-2.1 regulated, Wang et al 2003 S5 genes common to feeding ANOVA, Wang et al 2003 S3 genes pass one-way ANOVA T28B8.2 T28B8.2 Ceinsulin-1; igf-1; ins-18; T28B8.2; 1I725; CE27217; NM_059830; WBGene00002101; WP:CE27217 The ins-18 gene encodes an insulin/IGF-like peptide that may act in a common pathway with daf-2 to regulate lifespan. insulin-like growth factor I like Jones et al 2001 T2 lifespan and Dauer, Murphy et al 2003 Fig2 Class1 elongate lifespan, Reinke et al 2004, wt herm vs wt herm enriched gen, Reinke et al 2004, IVb male soma enriched genes, Wang et al 2003 S3 genes pass one-way ANOVA, Wang et al 2003 S4 Dauer Enriched, Wang et al 2003 S4 genes pass two-wayANOVA P0 Y54G11A.6 Y54G11A.6 ctl-1; Y54G11A.6; 2O592; CE30713; NM_064578; WBGene00000830; WP:CE30713; cat2 ctl-1 encodes a cytoplasmic catalase. catalase Jones et al 2001 T2 lifespan and Dauer, Murphy et al 2003 Fig2 Class1 elongate lifespan, ViswanathanM et al 2005 S2 sir-2.1 regulated Y55D5A.5 Y55D5A.5 daf-2; Y55D5A.5; Y55D5A_392.A; 3E86; CE27499; NM_065249; WBGene00000898; WP:CE27499 daf-2 encodes a predicted receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage, adult longevity, reproduction, fat storage, and response to exogenous stressors such as high temperature or bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary signals that coordinate growth and longevity throughout the animal. Jones et al 2001 T2 lifespan and Dauer, McCarroll et al 2004 SFig1-4 conserved w/ Drosoph, Reinke et al 2004, intrinsic, Reinke et al 2004, wt vs glp-4 enriched genes, Reinke et al 2004, list of genes in cluster order, Reinke et al 2004, list of genes in cluster E, Roy et al 2002 S3 muscle genes ZC395.2 ZC395.2 clk-1; coq-1; coq-7; ZC395.2; 3G369; CE01438; NM_065727; WBGene00000536; WP:CE01438 The clk-1 gene partially controls lifespan in vivo; it encodes a homolog of the yeast COQ9 protein, and is necessary for the biosynthesis of ubiquinone (UQ(9)) from demethoxyubiquinone (DMQ(9)). Jones et al 2001 T2 lifespan and Dauer, McCarroll et al 2004 SFig5 conserved w/ yeast, McCarroll et al 2004 SFig1-4 conserved w/ Drosoph, Romagnolo et al 2002 Fig3b Oxidation, Roy et al 2002 S3 muscle genes, ViswanathanM et al 2005 S2 sir-2.1 regulated ZC395.6 ZC395.6 gro-1; ZC395.6; 3G355; CE30119; NM_065721; WBGene00001740; WP:CE30119 This gene encodes a protein predicted by Eisenberg and coworkers, with 52% accuracy, to be mitochondrial. tRNA isopentenyltransferase Jones et al 2001 Non dauer genes P<0.05, Jones et al 2001 T2 lifespan and Dauer, McCarroll et al 2004 SFig5 conserved w/ yeast, Reinke et al 2004, list of genes in cluster order, Reinke et al 2004, intrinsic, Reinke et al 2004, wt vs glp-4 enriched genes, Reinke et al 2004, wt herm vs wt male enriched gen, Reinke et al 2004, list of genes in cluster E, ViswanathanM et al 2005 S2 sir-2.1 regulated ZK430.1 ZK430.1 T12C9.2; ZK430.1; 2E721; CE05078; WBGene00022739; WP:CE05078 Jones et al 2001 T2 lifespan and Dauer, McCarroll et al 2004 SFig1-4 conserved w/ Drosoph, Reinke et al 2004, intrinsic, Reinke et al 2004, wt vs glp-4 enriched genes, Reinke et al 2004, GO categories