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At least 19 recordsLinked to original sources

Comparative genomics in C. elegans, C. briggsae, and other Caenorhabditis species.

The genome of the nematode Caenorhabditis elegans was the first animal genome sequenced. Subsequent sequencing of the Caenorhabditis briggsae genome enabled a comparison of the genomes of two nematode species. In this chapter, we describe the methods that we used to compare the C. elegans genome to that of C. briggsae. We discuss how these methods could be developed to compare the C. elegans and C. briggsae genomes to those of Caenorhabditis remanei, C. n. sp. represented by strains PB2801 and CB5161, among others (1), and Caenorhabditis japonica, which are currently being sequenced.

Animals↗

The UNC-119 family of neural proteins is functionally conserved between humans, Drosophila and C. elegans.

C. elegans animals mutant for the unc-119 gene exhibit movement, sensory and behavioral abnormalities. Consistent with a nervous system role, unc-119 reporter genes are expressed throughout the C. elegans nervous system. The UNC-119 protein has strong sequence similarity to the predicted protein from a human gene, HRG4/HsUNC-119, whose transcript is abundant in the retina. Using these similarities, we have identified a Drosphila homolog, DmUNC-119, which is expressed in the Drosophila nervous system. The predicted C. elegans, human and Drosophila gene products are conserved across two domains. Expression of portions of HRG4/HsUNC-119 or DmUNC-119, directed by the unc-119 promoter, can fully rescue the C. elegans unc-119 mutant phenotype. We tested the ability of portions of HRG4/HsUNC-119 to rescue, and found that its function in C. elegans requires the conserved carboxyl terminus, while the dissimilar amino terminus is dispensable. UNC-119, HRG4 and DmUNC-119 constitute members of a new class of neural genes whose common function has been maintained through metazoan evolution.

Adaptor Proteins, Signal Transducing↗

Activation of nicotinic receptors uncouples a developmental timer from the molting timer in C. elegans.

C. elegans develops through four larval stages (L1 to L4) separated by molts. The identity of larval stages is mostly determined by stage-specific expression of heterochronic genes, which constitute an intrinsic genetic timer. However, extrinsic cues such as food availability or population density also modulate the developmental timing of C. elegans by mechanisms that remain largely unknown. To investigate a potential role of the nervous system in the temporal regulation of C. elegans development, we pharmacologically manipulated nicotinic neurotransmission, which represents a prominent signaling component in C. elegans nervous system. Exposure to the nicotinic agonist DMPP during post-embryonic development is lethal at the L2/L3 molt. Specifically, it delays cell divisions and differentiation during the L2 stage but does not affect the timing of the molt cycle, hence causing exposure of a defective L3 cuticle to the environment after the L2/L3 molt. Forcing development through a previously uncharacterized L2 diapause resynchronizes these events and suppresses DMPP-induced lethality. Nicotinic acetylcholine receptors (nAChRs) containing the UNC-63 subunit are required, probably in neurons, to trigger the action of DMPP. Using a forward genetic screen, we further demonstrated that the nuclear hormone receptor (NHR) DAF-12 is necessary to implement the developmental effects of DMPP. Therefore, a novel neuroendocrine pathway involving nAChRs and the NHR DAF-12 can control the speed of stage-specific developmental events in C. elegans. Activation of DMPP-sensitive nAChRs during the second larval stage uncouples a molting timer and a developmental timer, thus causing a heterochronic phenotype that is lethal at the subsequent molt.

Animals↗

NemaFootPrinter: a web based software for the identification of conserved non-coding genome sequence regions between C. elegans and C. briggsae.

BACKGROUND: NemaFootPrinter (Nematode Transcription Factor Scan Through Philogenetic Footprinting) is a web-based software for interactive identification of conserved, non-exonic DNA segments in the genomes of C. elegans and C. briggsae. It has been implemented according to the following project specifications:a) Automated identification of orthologous gene pairs. b) Interactive selection of the boundaries of the genes to be compared. c) Pairwise sequence comparison with a range of different methods. d) Identification of putative transcription factor binding sites on conserved, non-exonic DNA segments. RESULTS: Starting from a C. elegans or C. briggsae gene name or identifier, the software identifies the putative ortholog (if any), based on information derived from public nematode genome annotation databases. The investigator can then retrieve the genome DNA sequences of the two orthologous genes; visualize graphically the genes' intron/exon structure and the surrounding DNA regions; select, through an interactive graphical user interface, subsequences of the two gene regions. Using a bioinformatics toolbox (Blast2seq, Dotmatcher, Ssearch and connection to the rVista database) the investigator is able at the end of the procedure to identify and analyze significant sequences similarities, detecting the presence of transcription factor binding sites corresponding to the conserved segments. The software automatically masks exons. DISCUSSION: This software is intended as a practical and intuitive tool for the researchers interested in the identification of non-exonic conserved sequence segments between C. elegans and C. briggsae. These sequences may contain regulatory transcriptional elements since they are conserved between two related, but rapidly evolving genomes. This software also highlights the power of genome annotation databases when they are conceived as an open resource and the possibilities offered by seamless integration of different web services via the http protocol. AVAILABILITY: The program is freely available at http://bio.ifom-firc.it/NTFootPrinter.

Animals↗

Generation and modulation of chemosensory behaviors in C. elegans.

C. elegans recognizes and discriminates among hundreds of chemical cues using a relatively compact chemosensory nervous system. Chemosensory behaviors are also modulated by prior experience and contextual cues. Because of the facile genetics and genomics possible in this organism, C. elegans provides an excellent system in which to explore the generation of chemosensory behaviors from the level of a single gene to the motor output. This review summarizes the current knowledge on the molecular and neuronal substrates of chemosensory behaviors and chemosensory behavioral plasticity in C. elegans.

Adaptation, Biological↗

Translational regulation of tra-2 by its 3' untranslated region controls sexual identity in C. elegans.

C. elegans hermaphrodites make sperm and then oocytes in an otherwise female animal. Gain-of-function mutations in the sex-determining gene tra-2 (tra-2(gf)) transform hermaphrodites into females (spermless hermaphrodites). The tra-2(gf) mutations map to a perfect direct repeat in the 3' untranslated region; each repeat is called a direct repeat element (DRE). Three experiments demonstrate that DREs repress tra-2 at the translational level. First, tra-2(gf) mRNAs are associated with larger polysomes than are their wild-type counterparts. Second, translation of a reporter RNA is inhibited by DREs. Third, disruption of DREs does not increase tra-2 mRNA levels. An RNA binding activity specifically associates with the DREs. We propose that tra-2 translation is inhibited by association of an RNA binding-factor with the DREs and that this translational control is essential for development of C. elegans as a hermaphrodite/male species.

Animals↗

Analysis of the effects of turning bias on chemotaxis in C. elegans.

C. elegans advances up a chemical gradient by modulating the probability of occasional large, course-correcting turns called pirouettes. However, it remains uncertain whether C. elegans also uses other behavioral strategies for chemotaxis. Previous observations of the unusual, spiral-shaped chemotaxis tracks made by the bent-head mutant unc-23 point to a different strategy in which the animal continuously makes more subtle course corrections. In the present study we have combined automated tracking of individual animals with computer modeling to test the hypothesis that the pirouette strategy is sufficient on its own to account for the spiral tracks. Tracking experiments showed that the bent-head phenotype causes a strong turning bias and disrupts pirouette execution but does not disrupt pirouette initiation. A computer simulation of disrupted pirouette behavior and turning bias reproduced the spiral tracks of unc-23 chemotaxis behavior, showing that the pirouette strategy is sufficient to account for the mutant phenotype. In addition, the simulation reproduced higher order features of the behavior such as the relationship between the handedness of the spiral and the side to which the head was bent. Our results suggest that the pirouette mechanism is sufficient to account for a diverse range of chemotaxis trajectories.

Animals↗

Cellular and molecular analyses of olfactory behavior in C. elegans.

C. elegans responds to and discriminates among a large number of volatile and water-soluble chemicals using a few defined chemosensory neurons. The functions of individual sensory neurons have been defined by cell killing experiments, and genes required for responses to subsets of chemicals have been identified. C. elegans has several large families of putative chemosensory receptor genes, and one of these genes has been demonstrated to encode a receptor for a specific odorant. Current work is aimed at identifying additional components of chemosensory neuron development and function.

Journal Article↗

aex-3 encodes a novel regulator of presynaptic activity in C. elegans.

C. elegans aex-3 mutations cause pleiotropic behavioral defects that are suggestive of reduced synaptic transmission. aex-3 mutations also show strong genetic interactions with mutations in unc-31 and unc-64, two other genes implicated in synaptic transmission. Physiological and pharmacological studies indicate that aex-3 defects are presynaptic. In aex-3 mutants, the synaptic vesicle-associated RAB-3 protein aberrantly accumulates in neuronal cell bodies and is reduced in synapse-rich axons. This localization defect is specific to RAB-3, since other synaptic proteins are localized normally in aex-3 mutants. aex-3 encodes a 1409 amino acid protein with strong homology to DENN, a human protein of unknown function. In C. elegans, aex-3 is expressed in all or nearly all neurons. These results suggest that AEX-3 is a novel regulator of presynaptic activity that interacts with RAB-3 to regulate synaptic vesicle release.

Aldicarb↗

Lateral signaling mediated by axon contact and calcium entry regulates asymmetric odorant receptor expression in C. elegans.

C. elegans detects several odorants with the bilaterally symmetric pair of AWC olfactory neurons. A stochastic, coordinated decision ensures that the candidate odorant receptor gene str-2 is expressed in only one AWC neuron in each animal--either the left or the right neuron, but never both. An interaction between the two AWC neurons generates asymmetric str-2 expression in a process that requires normal axon guidance and probably AWC axon contact. This interaction induces str-2 expression by reducing calcium signaling through a voltage-dependent Ca2+ channel and the CaM kinase II UNC-43. CaMKII activity acts as a switch in the initial decision to express str-2; thus, calcium signals can define distinct cell types during neuronal development. A cGMP signaling pathway that is used in olfaction maintains str-2 expression after the initial decision has been made.

Animals↗

Identification of a microtubule-based cytoplasmic motor in the nematode C. elegans.

C. elegans contains a microtubule binding protein that resembles both dynein and kinesin. This protein has a MgATPase activity and copurifies on both sucrose gradients and DEAE Sephadex columns with a polypeptide of Mr approximately 400 kd. The ATPase activity is 50% inhibited by 10 microM vanadate, 1 mM N-ethyl maleimide, or 5 mM AMP-PNP; it is enhanced 50% by 0.2% Triton. The 400 kd polypeptide is cleaved at a single site by ultraviolet light in the presence of ATP and vanadate. In these ways, the protein resembles dynein. The protein also promotes ATP-dependent translocation of microtubules or axonemes, "plus" ends trailing. This property is kinesin-like; however, the motility is blocked by 5 microM vanadate, 1 mM N-ethyl maleimide, 0.5 mM ATP-gamma-S, or by ATP-vanadate-UV cleavage of the 400 kd polypeptide, characteristics that differ from kinesin. We propose that this protein is a novel microtubule translocator.

Adenosine Triphosphatases↗

Differences in non-LTR retrotransposons within C. elegans and C. briggsae genomes.

An exhaustive study of the Sam/Frodo family of non-LTR retrotransposons in the Caenorhabditis elegans and Caenorhabditis briggsae genomes demonstrated that C. briggsae contains 60 Sam/Frodo elements including a new subfamily designated Merry, while at least 1000 elements are present in C. elegans. In contrast to C. elegans, C. briggsae does not contain any other non-LTR retrotransposons. The Sam/Frodo/Merry sequences in C. briggsae are shorter and less complete than the Sam/Frodo sequences in C. elegans probably because they all lack a functional first open reading frame (ORF1) and because the genome only encodes one functional reverse transcriptase gene of a non-LTR retrotransposon. Evidence of purifying selection for a functional reverse transcriptase sequence in master/leader elements was found in both nematodes in spite of low copy numbers in C. briggsae. Sam elements in C. elegans are the most abundant Sam/Frodo/Merry family members. They contain the only functional ORF1 copies and, unlike Frodo and Merry members, have a higher GC content than the genomic regions in which they reside. This may indicate a higher transcription rate within this subfamily.

Animals↗

Conservation of sequence and function of the pag-3 genes from C. elegans and C. briggsae.

The Caenorhabditis briggsae homologue of the Caenorhabditis elegans pag-3 gene was cloned and sequenced. When transformed into a C. elegans pag-3 mutant, the C. briggsae pag-3 gene rescued the pag-3 reverse kinker and lethargic phenotypes. The C. elegans pag-3 gene fused to lacZ was expressed in the same pattern in C. elegans and C. briggsae. Unlike many gene homologues compared between C. elegans and C. briggsae, extensive sequence conservation was found in the non-coding regions upstream of the pag-3 exons, in several of the introns and in the downstream non-coding region. Furthermore, the splice acceptor and splice donor sites were conserved, and the size of the introns and exons was surprisingly similar. The predicted protein sequence of C. briggsae PAG-3 was 85% identical to the protein sequence of C. elegans PAG-3. Because so much of the non-coding region of pag-3 was conserved, the control of pag-3 may be quite complex, involving the binding of many trans-acting factors. These results suggest the evolutionary conservation of the pag-3 gene sequence, its expression and function.

Amino Acid Sequence↗

Pattern of selective constraint in C. elegans and C. briggsae genomes.

Similarity between related genomes may carry information on selective constraint in each of them. We analysed patterns of similarity between several homologous regions of Caenorhabditis elegans and C. briggsae genomes. All homologous exons are quite similar. Alignments of introns and of intergenic sequences contain long gaps, segments where similarity is low and close to that between random sequences aligned using the same parameters, and segments of high similarity. Conservative estimates of the fractions of selectively constrained nucleotides are 72%, 17% and 18% for exons, introns and intergenic sequences, respectively. This implies that the total number of constrained nucleotides within non-coding sequences is comparable to that within coding sequences, so that at least one-third of nucleotides in C. elegans and C. briggsae genomes are under strong stabilizing selection.

Animals↗

The perfect C. elegans project: an initial report.

The soil nematode Caenorhabditis Elegans (C. elegans) is the most investigated of all multicellular organisms. Since the proposal to use it as a model organism, a series of research projects have been undertaken, investigating various aspects of this organism. As a result, the complete cell lineage, neural circuitry, and various genes and their functions have been identified. The complete C. elegans DNA sequencing and gene expression mapping for each cell at different times during embryogenesis will be identified in a few years. Given the abundance of collected data, we believe that the time is ripe to introduce synthetic models of C. elegans to further enhance our understanding of the underlying principles of its development and behavior. For this reason, we have started the Perfect C. elegans Project, which aims to produce ultimately a complete synthetic model of C. elegans' cellular structure and function. This article describes the goal, the approach, and the initial results of the project.

Animals↗

A model of motor control of the nematode C. elegans with neuronal circuits.

OBJECTIVE: Living organisms have mechanisms to adapt to various conditions of external environments. If we can realize these mechanisms on the computer, it may be possible to apply methods of biological and biomimetic adaptation to the engineering of artificial machines. This paper focuses on the nematode Caenorhabditis elegans (C. elegans), which has a relatively simple structure and is one of the most studied multicellular organisms. We aim to develop its computer model, artificial C. elegans, to analyze control mechanisms with respect to motion. Although C. elegans processes many kinds of external stimuli, we focused on gentle touch stimulation. METHODS: The proposed model consists of a neuronal circuit model for motor control that responds to gentle touch stimuli and a kinematic model of the body for movement. All parameters included in the neuronal circuit model are adjusted by using the real-coded genetic algorithm. Also, the neuronal oscillator model is employed in the body model to generate the sinusoidal movement. The motion velocity of the body model is controlled by the neuronal circuit model so as to correspond to the touch stimuli that are received in sensory neurons. CONCLUSION: The computer simulations confirmed that the proposed model is capable of realizing motor control similar to that of the actual organism qualitatively. By using the artificial organism it may be possible to clarify or predict some characteristics that cannot be measured in actual experiments. With the recent development of computer technology, such a computational analysis becomes a real possibility. The artificial C. elegans will contribute for studies in experimental biology in future, although it is still developing at present.

Algorithms↗

Inheritance of Factors Affecting Floral Primordia Initiation in Cestrum; Hybrids of C. elegans and C. nocturnum.

Photoperiod patterns of hybrids of Cestrum elegans (Brongn.) Schlect., a day neutral plant, and C. nocturnum L., a long-short day and long day plant, were investigated. Plants of the F(1) generation, F(2) generation, and backcrosses to each parent were tested on short day, long day, continuous light, long-short day and short-long day for floral primordia initiation. The data recorded suggest 2 independent genes or gene groups controlling floral primordia initiation in C. nocturnum, a single dominant gene that is activated by long-short day treatment and a recessive gene or genes responding to long day treatment. Further, these data suggest that the day neutral condition in C. elegans is the result of the series of independent genes or gene groups that respond to various photoperiods, the combination of these genes resulting in floral primordia initiation on all photoperiods.

Journal Article↗

State-dependency in C. elegans.

Memory and the expression of learned behaviors by an organism are often triggered by contextual cues that resemble those that were present when the initial learning occurred. In state-dependent learning, the cue eliciting a learned behavior is a neuroactive drug; behaviors initially learned during exposure to centrally acting compounds such as ethanol are subsequently recalled better if the drug stimulus is again present during testing. Although state-dependent learning is well documented in many vertebrate systems, the molecular mechanisms underlying state-dependent learning and other forms of contextual learning are not understood. Here we demonstrate and present a genetic analysis of state- dependent adaptation in Caenorhabditis elegans. C. elegans normally exhibits adaptation, or reduced behavioral response, to an olfactory stimulus after prior exposure to the stimulus. If the adaptation to the olfactory stimulus is acquired during ethanol administration, the adaptation is subsequently displayed only if the ethanol stimulus is again present. cat-1 and cat-2 mutant animals are defective in dopaminergic neuron signaling and are impaired in state dependency, indicating that dopamine functions in state-dependent adaptation in C. elegans.

Adaptation, Physiological↗