Model organisms: The nematode worm

29/8/02. By Richard Twyman

The nematode worm Caenorhabditis elegans is a very simple animal that can be handled like a microbe but it shares many genes and molecular pathways with humans.

Caenorhabditis elegans is a soil-dwelling nematode worm about 1 mm in length that feeds on bacteria. It is one of two major model organisms representing the invertebrates. The other is the fruit fly Drosophila melanogaster.

While the fruit fly has a long history as a model organism this is not the case for the nematode. C. elegans was chosen in 1963 specifically to provide a new model for scientists studying animal development. It was chosen because it is perhaps the simplest multicellular organism in existence, containing fewer than 1000 somatic cells. Despite this simplicity, C. elegans has a multitude of cell types and a fully functioning nervous system. It therefore shares enough characteristics with humans to be a useful model.

One of the most attractive features of C. elegans is that it can be handled like a microbe. Large numbers of worms can be maintained inexpensively on lawns of bacteria growing on standard agar plates, but viable cultures can be stored as frozen stocks and then revived when required. Unlike other animals, C. elegans does not have male and female sexes. Instead, there are males and hermaphrodites. A single hermaphrodite can self-fertilise and produce over 1000 eggs per day. If crosses need to be carried out, hermaphrodites can be mated with males. The life cycle of C. elegans is two weeks long, similar to that of the fruit fly, so it is very amenable to genetic analysis.

The rise of the nematode worm as a model organism began in 1963, when Sydney Brenner chose it for his studies of the role of genes in development and the nervous system.

C. elegans also has an impressive list of experimental advantages. The worm is transparent throughout its life. Therefore, the behaviour of individual cells can be followed through development and gene expression patterns can be monitored very easily. A unique feature of this animal is that development is stereotypical, i.e. cells divide and specialise in a totally characteristic way so that every normal worm has the same number and type of cells arranged in the same manner. This means that the lineage of every cell can be traced back to the egg. A complete wiring map of the 302 neurons that make up the nervous system is also available. C. elegans mutants can be produced very easily and gene function can also be studied using the relatively new technique of RNA interference.

The C. elegans genome is 97 million base pairs in length and contains about 20 000 genes. Many of these genes appear to have functional counterparts in humans, and whole pathways are often conserved. This makes C. elegans a useful model for human diseases. For example, the insulin signalling pathway is fully conserved between humans and nematodes so mutant worms impaired for insulin signalling are useful models of type II diabetes. Due to their microbe-like properties, these nematode mutants can be screened with thousands of potential drugs to identify compounds that return the insulin-insensitive disease physiology to normal. C. elegans mutants provide models of many other diseases including neurological disorders, congenital heart disease and kidney disease. The molecular basis of cell death has been studied extensively in C. elegans and in the future this worm may even hold the key to counteracting the effects of ageing in humans.

Further reading

Feature: Why the worm?

The C. elegans Sequencing Consortium. Genome Sequence of the Nematode Caenorhabditis elegans. A Platform for Investigating Biology. Science (1998) 282:2012-2018. Abstract