Sulston JE et al. (1992) Nature "The C. elegans genome sequencing project: a beginning."

Wilson RK, Metzstein MM, Ainscough R, Waterston RH, Coulson AR, Craxton M, Thomas K, Dear S, Qiu L, Staden R, Berks M, Halloran N, Thierry-Mieg J, Hillier L, Sulston JE, Du Z, Durbin RM, Hawkins TL, Green P

[Nature, 1992]

The long-term goal of this project is the elucidation of the complete sequence of the Caenorhabditis elegans genome. During the first year methods have been developed and a strategy implemented that is amenable to large-scale sequencing. The three cosmids sequenced in this initial phase are surprisingly rich in genes, many of which have mammalian homologues.AD - MRC Laboratory of Molecular Biology, Cambridge, UK.FAU - Sulston, JAU - Sulston JFAU - Du, ZAU - Du ZFAU - Thomas, KAU - Thomas KFAU - Wilson, RAU - Wilson RFAU - Hillier, LAU - Hillier LFAU - Staden, RAU - Staden RFAU - Halloran, NAU - Halloran NFAU - Green, PAU - Green PFAU - Thierry-Mieg, JAU - Thierry-Mieg JFAU - Qiu, LAU - Qiu LAU - et al.LA - engPT - Journal ArticleCY - ENGLANDTA - NatureJID - 0410462RN - 0 (Cosmids)SB - IM

Vassilieva LL et al. (1999) Genetics "The rate of spontaneous mutation for life-history traits in Caenorhabditis elegans."

Vassilieva LL, Lynch M

[Genetics, 1999]

Spontaneous mutations were accumulated in 100 replicate lines of Caenorhabditis elegans over a period of approximately 50 generations. Periodic assays of these lines and comparison to a frozen control suggest that the deleterious mutation rate for typical life-history characters in this species is at least 0.05 per diploid genome per generation, with the average mutational effect on the order of 14% or less in the homozygous state and the average mutational heritability approximately 0.0034. While the average mutation rate per character and the average mutational heritability for this species are somewhat lower than previous estimates for Drosophila, these differences can be reconciled to a large extent when the biological differences between these species are taken into consideration.AD - Department of Biology, University of Oregon, Eugene, Oregon 97403, USA.larissa@darkwing.uoregon.eduFAU - Vassilieva, L LAU - Vassilieva LLFAU - Lynch, MAU - Lynch MLA - engID - RO1-GM36827/GM/NIGMSPT - Journal ArticleCY - UNITED STATESTA - GeneticsJID - 0374636SB - IM

Legouis R et al. (2000) Nat Cell Biol "LET-413 is a basolateral protein required for the assembly of adherens junctions in Caenorhabditis elegans."

Sookhareea S, Gansmuller A, Legouis R, Baillie DL, Bosher JM, Labouesse M

[Nat Cell Biol, 2000]

Epithelial cells are polarized, with apical and basal compartments demarcated by tight and adherens junctions. Proper establishment of these subapical junctions is critical for normal development and histogenesis. We report the characterization of the gene let-413 which has a critical role in assembling adherens junctions in Caenorhabditis elegans. In let-413 mutants, adherens junctions are abnormal and mislocalized to more basolateral positions, epithelial cell polarity is affected and the actin cytoskeleton is disorganized. The LET-413 protein contains one PDZ domain and 16 leucine-rich repeats with high homology to proteins known to interact with small GTPases. Strikingly, LET-413 localizes to the basolateral membrane. We suggest that LET-413 acts as an adaptor protein involved in polarizing protein trafficking in epithelial cells.AD - Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France.FAU - Legouis, RAU - Legouis RFAU - Gansmuller, AAU - Gansmuller AFAU - Sookhareea, SAU - Sookhareea SFAU - Bosher, J MAU - Bosher JMFAU - Baillie, D LAU - Baillie DLFAU - Labouesse, MAU - Labouesse MLA - engSI - GENBANK/AJ276590PT - Journal ArticleCY - ENGLANDTA - Nat Cell BiolJID - 100890575RN - 0 (Helminth Proteins)RN - 0 (LET-413 protein)SB - IM

McIntire SL et al. (1993) Nature "The GABAergic nervous system of Caenorhabditis elegans."

Horvitz HR, Kaplan JM, McIntire SL, Jorgensen EM

[Nature, 1993]

gamma-Aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in vertebrates and invertebrates. GABA receptors are the target of anxiolytic, antiepileptic and antispasmodic drugs, as well as of commonly used insecticides. How does a specific neurotransmitter such as GABA control animal behaviour? To answer this question, we identified all neurons that react with antisera raised against the neurotransmitter GABA in the nervous system of the nematode Caenorhabditis elegans. We determined the in vivo functions of 25 of the 26 GABAergic neurons by killing these cells with a laser microbeam in living animals and by characterizing a mutant defective in GABA expression. On the basis of the ultrastructurally defined connectivity of the C. elegans nervous system, we deduced how these GABAergic neurons act to control the body and enteric muscles necessary for different behaviours. Our findings provide evidence that GABA functions as an excitatory as well as an inhibitory neurotransmitter.AD - Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139.FAU - McIntire, S LAU - McIntire SLFAU - Jorgensen, EAU - Jorgensen EFAU - Kaplan, JAU - Kaplan JFAU - Horvitz, H RAU - Horvitz HRLA - engPT - Journal ArticleCY - ENGLANDTA - NatureJID - 0410462RN - 56-12-2 (gamma-Aminobutyric Acid)SB - IM

Walhout AJM et al. (2000) Science "Protein interaction mapping in C. elegans using proteins involved in vulval development."

Sordella R, Hartley JL, Lu WX, Thierry-Mieg N, Walhout AJM, Brasch MA, Temple GF, Vidal MI

[Science, 2000]

Protein interaction mapping using large-scale two-hybrid analysis has been proposed as a way to functionally annotate large numbers of uncharacterized proteins predicted by complete genome sequences. This approach was examined in Caenorhabditis elegans, starting with 27 proteins involved in vulval development. The resulting map reveals both known and new potential interactions and provides a functional annotation for approximately 100 uncharacterized gene products. A protein interaction mapping project is now feasible for C. elegans on a genome-wide scale and should contribute to the understanding of molecular mechanisms in this organism and in human diseases.AD - Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.FAU - Walhout, A JAU - Walhout AJFAU - Sordella, RAU - Sordella RFAU - Lu, XAU - Lu XFAU - Hartley, J LAU - Hartley JLFAU - Temple, G FAU - Temple GFFAU - Brasch, M AAU - Brasch MAFAU - Thierry-Mieg, NAU - Thierry-Mieg NFAU - Vidal, MAU - Vidal MLA - engID - 1 R21 CA81658 A 01/CA/NCIID - 1 RO1 HG01715-01/HG/NHGRIPT - Journal ArticleCY - UNITED STATESTA - ScienceJID - 0404511RN - 0 (Genetic Vectors)RN - 0 (Helminth Proteins)RN - 0 (LIN-35 protein)RN - 0 (LIN-53 protein)RN - 0 (Repressor Proteins)RN - 0 (Retinoblastoma Protein)SB - IM

Reboul J et al. (2001) Nat Genet "Open-reading-frame sequence tags (OSTs) support the existence of at least 17,300 genes in C. elegans."

Doucette-Stamm L, Lamesch PE, Reboul J, Temple GF, Hartley JL, Brasch MA, Hill DE, Vaglio P, Thierry-Mieg N, Shin-i T, Lee H, Moore T, Vandenhaute J, Kohara Y, Vidal M, Jackson C, Thierry-Mieg J, Tzellas N, Thierry-Mieg D, Hitti J

[Nat Genet, 2001]

The genome sequences of Caenorhabditis elegans, Drosophila melanogaster and Arabidopsis thaliana have been predicted to contain 19,000, 13,600 and 25,500 genes, respectively. Before this information can be fully used for evolutionary and functional studies, several issues need to be addressed. First, the gene number estimates obtained in silico and not yet supported by any experimental data need to be verified. For example, it seems biologically paradoxical that C. elegans would have 50% more genes than Drosophilia. Second, intron/exon predictions need to be tested experimentally. Third, complete sets of open reading frames (ORFs), or "ORFeomes," need to be cloned into various expression vectors. To address these issues simultaneously, we have designed and applied to C. elegans the following strategy. Predicted ORFs are amplified by PCR from a highly representative cDNA library using ORF-specific primers, cloned by Gateway recombination cloning and then sequenced to generate ORF sequence tags (OSTs) as a way to verify identity and splicing. In a sample (n=1,222) of the nearly 10,000 genes predicted ab initio (that is, for which no expressed sequence tag (EST) is available so far), at least 70% were verified by OSTs. We also observed that 27% of these experimentally confirmed genes have a structure different from that predicted by GeneFinder. We now have experimental evidence that supports the existence of at least 17,300 genes in C. elegans. Hence we suggest that gene counts based primarily on ESTs may underestimate the number of genes in human and in other organisms.AD - Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.FAU - Reboul, JAU - Reboul JFAU - Vaglio, PAU - Vaglio PFAU - Tzellas, NAU - Tzellas NFAU - Thierry-Mieg, NAU - Thierry-Mieg NFAU - Moore, TAU - Moore TFAU - Jackson, CAU - Jackson CFAU - Shin-i, TAU - Shin-i TFAU - Kohara, YAU - Kohara YFAU - Thierry-Mieg, DAU - Thierry-Mieg DFAU - Thierry-Mieg, JAU - Thierry-Mieg JFAU - Lee, HAU - Lee HFAU - Hitti, JAU - Hitti JFAU - Doucette-Stamm, LAU - Doucette-Stamm LFAU - Hartley, J LAU - Hartley JLFAU - Temple, G FAU - Temple GFFAU - Brasch, M AAU - Brasch MAFAU - Vandenhaute, JAU - Vandenhaute JFAU - Lamesch, P EAU - Lamesch PEFAU - Hill, D EAU - Hill DEFAU - Vidal, MAU - Vidal MLA - engID - R21 CA81658 A 01/CA/NCIID - RO1 HG01715-01/HG/NHGRIPT - Journal ArticleCY - United StatesTA - Nat GenetJID - 9216904SB - IM

McIntire SL et al. (1993) Nature "Genes required for GABA function in Caenorhabditis elegans."

Jorgensen EM, Horvitz HR, McIntire SL

[Nature, 1993]

gamma-Aminobutyric acid (GABA) neurotransmission is widespread in vertebrate and invertebrate nervous systems. Here we use a genetic approach to identify molecules specific to GABA function. On the basis of the known in vivo roles of GABAergic neurons in controlling behaviour of the nematode Caenorhabditis elegans, we identified mutants defective in GABA-mediated behaviours. Five genes are necessary either for GABAergic neuronal differentiation or for pre- or postsynaptic GABAergic function. The gene unc-30 is required for the differentiation of a specific type of GABAergic neuron, the type-D inhibitory motor neuron. The gene unc-25 is necessary for GABA expression and probably encodes the GABA biosynthetic enzyme glutamic acid decarboxylase. The genes unc-46 and unc-47 seem to be required for normal GABA release. Finally, the gene unc-49 is apparently necessary postsynaptically for the inhibitory effect of GABA on the body muscles and might encode a protein needed for the function of a GABAA-like receptor. Some of these genes are likely to encode previously unidentified proteins required for GABA function.AD - Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.FAU - McIntire, S LAU - McIntire SLFAU - Jorgensen, EAU - Jorgensen EFAU - Horvitz, H RAU - Horvitz HRLA - engPT - Journal ArticleCY - ENGLANDTA - NatureJID - 0410462RN - 0 (Nipecotic Acids)RN - 2763-96-4 (Muscimol)RN - 498-95-3 (nipecotic acid)RN - 56-12-2 (gamma-Aminobutyric Acid)RN - 56879-46-0 (homoproline)SB - IM

Robins H et al. (2005) Proc Natl Acad Sci U S A. "Incorporating structure to predict microRNA targets."

Li Y, Robins H, Padgett RW

[Proc Natl Acad Sci U S A., 2005]

MicroRNAs (miRNAs) are a recently discovered set of regulatory genes that constitute up to an estimated 1% of the total number of genes in animal genomes, including Caenorhabditis elegans, Drosophila, mouse, and humans [Lagos-Quintana, M., Rauhut, R., Lendeckel, W. M Tuschl, T. (2001) Science 294, 853-858; Lai, E. C., Tomancak, P., Williams, R. W. M Rubin, G.M. (2003) Genome Biol. 4, R42; Lau, N. C., Lim, L. P., Weinstein, E. G. M Bartel, D. P. (2001) Science 294, 858-862; Lee, R. C. M Ambros, V. (2001) Science 294, 862-8644; and Lee, R. C., Feinbaum, R. L. M Ambros, V. (1993) Cell 115, 787-798]. In animals, miRNAs regulate genes by attenuating protein translation through imperfect base pair binding to 3' UTR sequences of target genes. A major challenge in understanding the regulatory role of miRNAs is to accurately predict regulated targets. We have developed an algorithm for predicting targets that does not rely on evolutionary conservation. As one of the features of this algorithm, we incorporate the folded structure of mRNA. By using Drosophila miRNAs as a test case, we have validated our predictions in 10 of 15 genes tested. One of these validated genes is mad as a target for bantam. Furthermore, our computational and experimental data suggest that miRNAs have fewer targets than previously reported.

Tissenbaum HA et al. (2001) Nature "Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans."

Guarente L, Tissenbaum HA

[Nature, 2001]

In Caenorhabditis elegans, mutations that reduce the activity of an insulin-like receptor (daf-2) or a phosphatidylinositol-3-OH kinase (age-1) favour entry into the dauer state during larval development and extend lifespan in adults. Downregulation of this pathway activates a forkhead transcription factor (daf-16), which may regulate targets that promote dauer formation in larvae and stress resistance and longevity in adults. In yeast, the SIR2 gene determines the lifespan of mother cells, and adding an extra copy of SIR2 extends lifespan. Sir2 mediates chromatin silencing through a histone deacetylase activity that depends on NAD (nicotinamide adenine dinucleotide) as a cofactor. We have surveyed the lifespan of C. elegans strains containing duplications of chromosomal regions. Here we report that a duplication containing sir-2.1-the C. elegans gene most homologous to yeast SIR2-confers a lifespan that is extended by up to 50%. Genetic analysis indicates that the sir-2.1 transgene functions upstream of daf-16 in the insulin-like signalling pathway. Our findings suggest that Sir2 proteins may couple longevity to nutrient availability in many eukaryotic organisms.AD - Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.FAU - Tissenbaum, H AAU - Tissenbaum HAFAU - Guarente, LAU - Guarente LLA - engPT - Journal ArticleCY - EnglandTA - NatureJID - 0410462RN - 0 (DAF-16 transcription factor)RN - 0 (Helminth Proteins)RN - 0 (Trans-Activators)RN - 0 (Transcription Factors)RN - EC 3.5.1.- (Histone Deacetylase)RN - EC 3.5.1.- (SIR2 protein)SB - IM