Caenorhabditis elegans

Overview
Caenorhabditis elegans is a free-living nematode (roundworm), about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model organism.

Biology
C. elegans is unsegmented, vermiform, bilaterally symmetrical, with a cuticle integument, four main epidermal cords and a fluid-filled pseudocoelomate cavity. Members of the species have many of the same organ systems as other animals. In the wild, they feed on bacteria that develop on decaying vegetable matter. Individuals of C. elegans are almost all hermaphrodite, with males comprising just 0.05% of the total population on average. The basic anatomy of C. elegans includes a mouth, pharynx, intestine, gonad, and collagenous cuticle. Males have a single-lobed gonad, vas deferens, and a tail specialized for mating. Hermaphrodites have two ovaries, oviducts, spermatheca, and a single uterus.

C. elegans eggs are laid by the hermaphrodite. After hatching, they pass through four larval stages (L1-L4). When crowded or in the absence of food, C. elegans can enter an alternative third larval stage called the dauer state. Dauer larvae are stress-resistant and do not age. Hermaphrodites produce all their sperm in the L4 stage (150 sperm per gonadal arm) and then switch over to producing oocytes. The sperm are stored in the same area of the gonad as the oocytes until the first oocyte pushes the sperm into the spermatheca (a kind of chamber where the oocytes become fertilized by the sperm). The male can inseminate the hermaphrodite, which will use male sperm preferentially (both types of sperm are stored in the spermatheca). When self-inseminated the wild-type worm will lay approximately 300 eggs. When inseminated by a male, the number of progeny can exceed 1,000. At 20°C, the laboratory strain of C. elegans has an average life span of approximately 2–3 weeks and a generation time of approximately 4 days. Hermaphrodites can mate with males or self-fertilize.

C. elegans has five pairs of autosomes and one pair of sex chromosomes. Sex in C. elegans is based on an X0 sex-determination system. Hermaphrodite C. elegans have a matched pair of sex chromosomes (XX); the rare males have only one sex chromosome (X0).



Laboratory uses
C. elegans is studied as a model organism for a variety of reasons. Strains are cheap to breed and can be frozen. When subsequently thawed they remain viable, allowing long-term storage. Because the complete cell lineage of the species has been determined, C. elegans has proven especially useful for studying cellular differentiation.

From a research perspective, C. elegans has the advantage of being a multicellular eukaryotic organism that is simple enough to be studied in great detail. The developmental fate of every single somatic cell (959 in the adult hermaphrodite; 1031 in the adult male) has been mapped out. These patterns of cell lineage are largely invariant between individuals, in contrast to mammals where cell development from the embryo is more largely dependent on cellular cues. In both sexes, a large number of additional cells (131 in the hermaphrodite, most of which would otherwise become neurons), are eliminated by programmed cell death (apoptosis).



In addition, C. elegans is one of the simplest organisms with a nervous system. In the hermaphrodite, this comprises 302 neurons whose pattern of connectivity has been completely mapped out, and shown to be a small-world network. Research has explored the neural mechanisms responsible for several of the more interesting behaviors shown by C. elegans, including chemotaxis, thermotaxis, mechanotransduction, and male mating behavior. Unusually, the neurons fire no action potentials.

A useful feature of C. elegans is that it is relatively straightforward to disrupt the function of specific genes by RNA interference (RNAi). Silencing the function of a gene in this way can sometimes allow a researcher to infer what the function of that gene may be. The nematode can either be soaked in (or injected with) a solution of double stranded RNA, the sequence of which is complementary to the sequence of the gene that the researcher wishes to disable. Alternatively, worms can be fed on genetically transformed bacteria which express the double stranded RNA of interest.

C. elegans has also been useful in the study of meiosis. As sperm and egg nuclei move down the length of the gonad, they undergo a temporal progression through meiotic events. This progression means that every nucleus at a given position in the gonad will be at roughly the same step in meiosis, eliminating the difficulties of heterogeneous populations of cells.

The organism has also been identified as a model for nicotine dependence as it has been found to experience the same symptoms humans experience when they quit smoking.

As for most model organisms, there is a dedicated online database for the species that is actively curated by scientists working in this field. The WormBase database attempts to collate all published information on C. elegans and other related nematodes. A reward of $5000 has been advertised on their website, for the finder of a new species of closely related nematode. Such a discovery would broaden research opportunities with the worm.

Genome
C. elegans was the first multicellular organism to have its genome completely sequenced. The finished genome sequence was published in 1998, although a number of small gaps were present (the last gap was finished by October 2002). The C. elegans genome sequence is approximately 100 million base pairs long and contains approximately 20,000 genes. The vast majority of these genes encode for proteins but there are likely to be as many as 1,000 RNA genes. Scientific curators continue to appraise the set of known genes, such that new gene predictions continue to be added and incorrect ones modified or removed.

In 2003, the genome sequence of the related nematode C. briggsae was also determined, allowing researchers to study the comparative genomics of these two organisms. Work is now ongoing to determine the genome sequences of more nematodes from the same genus such as C. remanei, C. japonica and C. brenneri. These newer genome sequences are being determined by using the whole genome shotgun technique which means that the resulting genome sequences are likely to not be as complete or accurate as C. elegans (which was sequenced using the 'hierarchical' or clone-by-clone appoach).

The official version of the C. elegans genome sequence continues to change as and when new evidence reveals errors in the original sequencing (DNA sequencing is not an error free process). Most changes are usually minor, adding or removing only a few base pairs (bp) of DNA. E.g. the WS169 release of WormBase (December 2006) lists a net gain of 6 bp to the genome sequence. Occasionally more extensive changes are made, e.g. the WS159 release of May 2006 added over 300 bp to the sequence.

Evolution
It has been shown that a small number of conserved protein sequences from sponges are more similar to humans than to C. elegans. This suggests that there has been an accelerated rate of evolution in the C. elegans lineage. The same study found that several phylogenetically ancient genes are not present in C. elegans.

Scientific community
In 2002, the Nobel Prize for Medicine was awarded to Sydney Brenner, H. Robert Horvitz and John Sulston for their work on the genetics of organ development and programmed cell death (PCD) in C. elegans. The 2006 Nobel Prize in Physiology or Medicine was awarded to Andrew Fire and Craig C. Mello, for their discovery of RNA interference in C. elegans.

Because all research into C. elegans essentially started with Sydney Brenner in the 1970's, many scientists working in this field share a close connection to Brenner (they either worked as a post-doctoral or post-graduate researcher in Brenner's lab or in the lab of someone who previously worked with Brenner). Because most people who worked in his lab went on to establish their own worm research labs, there is now a fairly well documented 'lineage' of C. elegans scientists. This lineage was recorded in some detail at the 2003 International Worm Meeting and the results were stored in the Wormbase database.

In the media
C. elegans made news when it was discovered that specimens had survived the Space Shuttle Columbia disaster in February 2003.

Publications



 * Gamulin, Vera; Müller, Isabel M. & Müller, Werner E. G. (2000): Sponge proteins are more similar to those of Homo sapiens than to Caenorhabditis elegans. Biol. J. Linn. Soc. 71(4): 821–828. HTML abstract





Online resources

 * WormBase - an extensive online database covering the biology and genomics of C. elegans and other nematodes
 * WormBook - a free online compendium of all aspects of C. elegans biology, including laboratory protocols
 * Wormatlas - an online database for behavioral and structural anatomy of C. elegans
 * Wellcome Trust Sanger Institute C. elegans page - half of the genome sequence is still maintained by this institute
 * WashU Genome Sequencing Center C. elegans page - the institute maintaining the other half of the genome
 * AceView WormGenes - another genome database for C. elegans, maintained at the NCBI
 * TCNJ Worm Lab - Easy to follow protocols and pictures for C. elegans research. Made by undergrads for undergrads.
 * Worm Classroom - An education portal for C. elegans
 * Textpresso - WormBase search engine
 * C. elegans movies - Timelapse films made by C. elegans researchers worldwide
 * C. elegans II - a free online textbook.
 * Silencing Genomes RNA interference (RNAi) experiments and bioinformatics in C. elegans for education. From the Dolan DNA Learning Center of Cold Spring Harbor Laboratory.
 * C.elegans 3D model by the Ewbank Lab - Videos and photos that explain the basic anatomy of C. elegans
 * WormTracker

Nobel lectures

 * Brenner S (2002) Nature's Gift to Science. In. http://nobelprize.org/nobel_prizes/medicine/laureates/2002/brenner-lecture.pdf
 * Horvitz HR (2002) Worms, Life and Death. In. http://nobelprize.org/nobel_prizes/medicine/laureates/2002/horvitz-lecture.pdf
 * Sulston JE (2002) The Cell Lineage and Beyond. In. http://nobelprize.org/nobel_prizes/medicine/laureates/2002/sulston-lecture.pdf