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[
WormBook,
2005]
In mammals, flies, and worms, sex is determined by distinctive regulatory mechanisms that cause males (XO or XY) and females (XX) to differ in their dose of X chromosomes. In each species, an essential X chromosome-wide process called dosage compensation ensures that somatic cells of either sex express equal levels of X-linked gene products. The strategies used to achieve dosage compensation are diverse, but in all cases, specialized complexes are targeted specifically to the X chromosome(s) of only one sex to regulate transcript levels. In C. elegans, this sex-specific targeting of the dosage compensation complex (DCC) is controlled by the same developmental signal that establishes sex, the ratio of X chromosomes to sets of autosomes (X:A signal). Molecular components of this chromosome counting process have been defined. Following a common step of regulation, sex determination and dosage compensation are controlled by distinct genetic pathways. C. elegans dosage compensation is implemented by a protein complex that binds both X chromosomes of hermaphrodites to reduce transcript levels by one-half. The dosage compensation complex resembles the conserved 13S condensin complex required for both mitotic and meiotic chromosome resolution and condensation, implying the recruitment of ancient proteins to the new task of regulating gene expression. Within each C. elegans somatic cell, one of the DCC components also participates in the separate mitotic/meiotic condensin complex. Other DCC components play pivotal roles in regulating the number and distribution of crossovers during meiosis. The strategy by which C. elegans X chromosomes attract the condensin-like DCC is known. Small, well-dispersed X-recognition elements act as entry sites to recruit the dosage compensation complex and to nucleate spreading of the complex to X regions that lack recruitment sites. In this manner, a repressed chromatin state is spread in cis over short or long distances, thus establishing the global, epigenetic regulation of X chromosomes that is maintained throughout the lifetime of hermaphrodites.
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[
WormBook,
2006]
The DNA in eukaryotes is wrapped around a histone octamer core, together comprising the main subunit of chromatin, the nucleosome. Modifications of the nucleosomal histones in the genome correlate with the ability or inability of chromatin to form higher order structures, that in turn influence gene activity. The genome in primordial germ cells in early C. elegans germ cells carries a unique pattern of histone modifications that correlate with transcriptional repression in these cells, and aspects of this chromatin regulation are conserved in Drosophila. Loss of repression causes sterility in the adults, suggesting that chromatin-based repression is essential for germ line maintenance. The post-embryonic germ line also exhibits unique and dynamic aspects of chromatin regulation, with chromosome-wide regulation particularly evident on the X chromosome. Several properties of X-specific chromatin assembly are also sex-specific. These properties appear to be responding to the meiotic pairing status of the X chromosome, rather than the sex of the germ cells. Finally, gamete-specific chromatin regulation during gametogenesis impacts on X chromatin assembly in the offspring, leading to an apparent sperm-imprinted X inactivation in the early embryo. Other potential roles for germline-specific modes of chromatin assembly in genome regulation and protection are discussed.
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[
WormBook,
2005]
The normal karyotype of Caenorhabditis elegans, with its five pairs of autosomes and single pair of X chromosomes, is described. General features of chromosomes and global differences between different chromosomal regions are discussed. Abnormal karyotypes, including duplications, deficiencies, inversions, translocations and chromosome fusions are reviewed. The effects of varying ploidy and of varying gene dosage are summarized. Dosage-sensitive genes seem to be rare in C. elegans, and the organism is able to tolerate substantial levels of aneuploidy. However, autosomal hemizygosity for more than about 3 % of the total genome may be incompatible with viability.
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[
WormBook,
2005]
C. elegans has emerged as a powerful genetic model organism in which to study synaptic function. Most synaptic proteins in the C. elegans genome are highly conserved and mutants can be readily generated by forward and reverse genetics. Most C. elegans synaptic protein mutants are viable affording an opportunity to study the functional consequences in vivo. Recent advances in electrophysiological approaches permit functional analysis of mutant synapses in situ. This has contributed to an already powerful arsenal of techniques available to study synaptic function in C. elegans. This review highlights C. elegans mutants affecting specific stages of the synaptic vesicle cycle, with emphasis on studies conducted at the neuromuscular junction.
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WormBook,
2005]
C. elegans presents a low level of molecular diversity, which may be explained by its selfing mode of reproduction. Recent work on the genetic structure of natural populations of C. elegans indeed suggests a low level of outcrossing, and little geographic differentiation because of migration. The level and pattern of molecular diversity among wild isolates of C. elegans are compared with those found after accumulation of spontaneous mutations in the laboratory. The last part of the chapter reviews phenotypic differences among wild isolates of C. elegans.
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WormBook,
2005]
This chapter reviews analytical tools currently in use for protein classification, and gives an overview of the C. elegans proteome. Computational analysis of proteins relies heavily on hidden Markov models of protein families. Proteins can also be classified by predicted secondary or tertiary structures, hydrophobic profiles, compositional biases, or size ranges. Strictly orthologous protein families remain difficult to identify, except by skilled human labor. The InterPro and NCBI KOG classifications encompass 79% of C. elegans protein-coding genes; in both classifications, a small number of protein families account for a disproportionately large number of genes. C. elegans protein-coding genes include at least ~12,000 orthologs of C. briggsae genes, and at least ~4,400 orthologs of non-nematode eukaryotic genes. Some metazoan proteins conserved in other nematodes are absent from C. elegans. Conversely, 9% of C. elegans protein-coding genes are conserved among all metazoa or eukaryotes, yet have no known functions.
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[
WormBook,
2007]
The soil nematode Caenorhabditis briggsae is an attractive model system for studying evolution of both animal development and behavior. Being a close relative of C. elegans, C. briggsae is frequently used in comparative studies to infer species-specific function of the orthologous genes and also for studying the dynamics of chromosome evolution. The genome sequence of C. briggsae is valuable in reverse genetics and genome-wide comparative studies. This review discusses resources and tools, which are currently available, to facilitate study of C. briggsae in order to unravel mechanisms of gene function that confer morphological and behavioral diversity.
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[
WormBook,
2005]
A wide variety of bacterial pathogens, as well as several fungi, kill C. elegans or produce non-lethal disease symptoms. This allows the nematode to be used as a simple, tractable model host for infectious disease. Human pathogens that affect C. elegans include Gram-negative bacteria of genera Burkholderia, Pseudomonas, Salmonella, Serratia and Yersinia; Gram-positive bacteria Enterococcus, Staphylococcus and Streptococcus; and the fungus Cryptococcus neoformans. Microbes that are not pathogenic to mammals, such as the insect pathogen Bacillus thuringiensis and the nematode-specific Microbacterium nematophilum, are also studied with C. elegans. Many of the pathogens investigated colonize the C. elegans intestine, and pathology is usually quantified as decreased lifespan of the nematode. A few microbes adhere to the nematode cuticle, while others produce toxins that kill C. elegans without a requirement for whole, live pathogen cells to contact the worm. The rapid growth and short generation time of C. elegans permit extensive screens for mutant pathogens with diminished killing, and some of the factors identified in these screens have been shown to play roles in mammalian infections. Genetic screens for toxin-resistant C. elegans mutants have identified host pathways exploited by bacterial toxins.
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WormBook,
2010]
An understanding of evolution at the molecular level requires the simultaneous consideration of the 5 fundamental evolutionary processes: mutation, recombination, natural selection, genetic drift, and population dynamic effects. Experimental, comparative genomic, and population genetic work in C. elegans has greatly expanded our understanding of these core processes, as well as of C. elegans biology. This chapter presents a brief overview of some of the most salient features of molecular evolution elucidated by the C. elegans system.
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WormBook,
2007]
As in all living organisms, survival in C. elegans requires adequate management of energy supplies. Genetic screens have revealed that C. elegans fat regulation involves a complex network of genes with known or likely functions in food sensation, neuroendocrine signaling, uptake, transport, storage and utilization of fats. Core fat and sugar metabolic pathways are conserved in C. elegans. Flux through these pathways is modulated by cellular energy sensors that operate via transcriptional and translational regulatory mechanisms. In turn, neuroendocrine mechanisms couple sensory and metabolic pathways while neuromodulatory pathways influence both metabolic and food seeking/consumption pathways. The shared ancestry of C. elegans and mammalian fat regulatory pathways extends to developmental programs that underlie fat storage capacity, despite lack of dedicated adipocytes, and genes whose human homologs are implicated in obesity. This suggests that many of the newly identified C. elegans fat regulatory pathways play similar roles in mammals. C. elegans is ideally suited for the integrated study of mechanisms that operate in multiple tissues and elicit feedback responses that affect processes as diverse as metabolism and behavior.