A Short History of C. elegans Research

Dr. Sydney BrennerDr. Sydney BrennerIn 1963, Sydney Brenner observed that the success of molecular biology was due to the existence of model systems, defined as extremely simple organisms, such as bacterial phage that can be handled in large numbers. With the awareness of how important model systems are in biological research, he introduced Caenorhabditis elegans (C. elegans) as a model organism for pursuing research in developmental biology and neurology.

Ever since its introduction by Brenner, C. elegans has been widely used in research laboratories (Wood, 1988). Due to its value as a research tool, a sophisticated knowledge infrastructure has developed, with freely disseminated research methods and protocols. The experimental attributes of C. elegans that make it successful in research laboratories also make it a favorable organism in teaching. Below, I will discuss the characteristics that make C. elegans so popular in research.

A Model Experimental System: Properties of C. elegans

Caenorhabditis elegans (Caeno, recent; rhabditis, rod; elegans, nice), is a free-living, non-parasitic soil nematode that can be safely used in the laboratory and is common around the world (Donald, 1997 1).

It is small (about 1 mm in length), transparent for ease of manipulation and observation, feeds on bacteria, such as E. coli, and it can be easily and cheaply housed and cultivated in large numbers (10,000 worms/petri dish) in the laboratory. C. elegans has five pairs of autosomes and one pair of sex chromosome. It has two sexes, hermaphrodites and males. Sexual determination in C. elegans is similar to Drosophila; the ratio of sex chromosomes to autosomes determines its sex. If the 6th chromosome pair is XX, then C. elegans will be a hermaphrodite. A XO combination in the 6th chromosome pair will produce a male. Hermaphrodites can self-fertilize or mate with males but cannot fertilize each other. In nature, hermaphrodites are the most common sex. When hermaphrodites mate with males, 50% of the progeny will be males and 50% will be hermaphrodites. In the laboratory, self-fertilization of hermaphrodites or crossing with males can be manipulated to produce progeny with desired genotypes that are especially useful for genetic study. In addition, C. elegans is extremely fecund-a hermaphrodite can produce about 300 to 350 offspring under self-fertilization and more if it mates with males. These traits make it easy to produce numerous genotypes and phenotypes for genetic research. (Donald, 1997; Horvitz, 19972; Wood, 1988 3).

C. elegans life cycle (click to enlarge)C. elegans life cycle (click to enlarge)In addition, C. elegans has a short life cycle. From egg to egg takes about 3 days, about the same time needed for genetic crosses in yeast. Its life span is around 2 to 3 weeks under suitable living condition. Compared to the use of other model organisms, such as mice, the short life cycle of C. elegans reduces the experimental cycle and facilitates biological study (Donald, 1997; Kenyon, 19884; Wood, 1988).

What is unique to this organism is that wild-type individuals contain a constant 959 cells. The position of cells is constant as is the cell number. Moreover, it is transparent. It is easy to track cells and follow cell lineages. The complete cell lineage, depicting which cells are derived from which, was completed in the 1980s by John Sulston. This provides a great tool for research on how genes influence cell fate. These traits enable the study of the biology of a single cell in an intact, living organism. Research on development and morphology can be done with a single cell within this multicellular organism (Donald, 1997; Horvitz, 20045; Kenyon, 1988; Wood, 1988).

C. elegans cell lineage (click to enlarge)C. elegans cell lineage (click to enlarge)The genome size of C. elegans is about a hundred million base pairs. This is approximately 20X bigger than that of E. coli and about 1/30 of that of human. The genome of C. elegans was completely sequenced at the end of 1998 (BBC, 1998). It is the first multicellular-organism (animal) that has a completely sequenced genome. Robert Waterston noted the value of this accomplishment when he said, "This is a tremendously gratifying moment and more of a beginning than an end. We have provided biologists with a powerful new tool to experiment with and learn how genomes function. We'll be able to ask-and answer questions we could never even think about before." Moreover, as its genome is surprisingly similar to that of humans (40% homologous), C. elegans becomes an attractive organism in the study of human diseases. For instance, in human leukemia, large numbers of immature white blood cells (WBCs), which normally die before getting into the blood stream, are in patients' blood circulation. The study of Programmed Cell Death (PCD, or apoptosis) in C. elegans might help us to understand why these immature WBCs didn't undergo PCD. In addition, the genome database of C. elegans is available worldwide. Researchers share their findings in C. elegans genome via the internet with other researchers from around the world. The process of sharing the genome database on the world wide web provides a working framework for researchers who are working on the human genome project (BBC, 19986; HGP, 1998 7; Hodgkin, Horvitz, Jasny, & Kimble, 1998 8; Horvitz, 2004; Kenyon, 1988; Muhlrad, 1998 9; Pennisi, 1998 10).

C. elegans mutants: a. normal, b. dumpy, c. small, d. longC. elegans mutants: a. normal, b. dumpy, c. small, d. longMoreover, there are many C. elegans mutants available for biological research, which is especially important for genetic study. Some genetically determined traits, such as motility mutants, are easy to observe. Therefore, powerful genetic experiments can be conducted using simple microscopes to observe the inheritance of traits in C. elegans mutants. When a mutant is found, it can be crossed with worms having a known genetic background and, further, one can learn where this mutated gene may be located and define its function.

Dr. John SulstonDr. John SulstonIn 1969, John Sulston developed a technique to freeze and thaw the worm. As a result, the numbers and availability of both wild type and mutated worms have increased (Donald, 1997). Moreover, many tools have been invented to speed up research using C. elegans. Advanced microscopes, various antibodies, different kinds of reporter genes for labeling and the use of laser microbeams to ablate individual cells are examples of such tools (Donald, 1997; Kenyon, 1988; Wood, 1988).

C. elegans is a model experimental organism that possesses simplicity, is small in size physically and genomically. It is multicellular and develops from a fertilized egg to an adult worm just as a human being does (Angier, 1995 11; Donald, 1997). In conclusion, the properties of C. elegans and the research done using C. elegans provide a wealth of information and an attractive pool of resources for researchers. Also, this well-established model system provides educators a good resource in teaching biology.

  • 1. Donald, D. L. (Ed.). (1997). C. elegans II. New York, NY: Cold Spring Harbor Laboratory Press.
  • 2. Horvitz, H. R. (1997). A nematode as a model organism: the genetics of programmed death [Film]. Cogito Learning Media, Inc. Available: http://www.cogitomedia.com [1999, Jul 20].
  • 3. Wood, W. B. (Ed.). (1988). The nematode Caenorhabditis elegans. New York, NY: Cold Spring Harbor Laboratory Press.
  • 4. Kenyon, C. (1988). The nematode Caenorhabditis elegans. Science, 240, 1448-1452.
  • 5. Horvitz, H. R. (2004). Genetic control of nematode development and behavior [on-line]. Available: http://www.hhmi.org/research/investigators/horvitz.html (2004, Dec 10).
  • 6. BBC. (1998, 10 Dec). Small worm makes history. BBC [on-line]. Available: http://news.bbc.co.uk/hi/english/sci/tech/newsid_232000/232608.stm [1999, Jun 9].
  • 7. HGP. (1998, Mar 12). Human genome project progress.[on-line]. Available: http://www.genome.gov/10001399 [2004, Dec10].
  • 8. Hodgkin, J., Horvitz, H. R., Jasny, B. R., & Kimble, J. (1998). C. elegans: sequence to biology. Science, 282, 2011.
  • 9. Muhlrad, P. (1998, Jul 8). Worms are a lot more similar to people than you may think [on-line]! Available: http://www.mcb.arizona.edu/wardlab/relevant.html [2004, Dec 10].
  • 10. Pennisi, E. (1998). Worming secrets from the C. elegans genome. Science, 282, 1972-1974.
  • 11. Angier, N. (1995). The beauty of the beastly: new views on the nature of life. Boston, MA: Houghton Mifflin.