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Recipe for a Worm

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Meet Caenorhabditis elegans, the world's most famous worm. Even enlarged it doesn't look like much. In real life, this short roundworm with a long name--so small that several could fit on the head of a pin--consists of fewer than a thousand cells. But on December 11, C. elegans won its place in the history books with the announcement that researchers at Washington University School of Medicine in St. Louis and the Sanger Centre in Cambridge, England, had decoded all of its genes--thus making the first complete genetic map for a higher organism.

Compared to humans, C. elegans seems a fairly lowly creature. Its genome contains a mere 97 million DNA base pairs, compared to more than three billion for Homo sapiens. But people have a surprising amount in common with this worm, which lives out its life rarely observed in the soil of temperate regions. Unlike the microbes sequenced so far, C. elegans begins life as a single, fertilized cell and undergoes a series of cell divisions as it grows into an adult animal, forming complex tissues and organs. Some 300 of the 959 cells of the adult worm, for example, constitute a nervous system that can detect odor, taste, and respond to temperature and touch. A digestive tube runs the length of the worm's body. During its two-to-three-week life span, finding a sex partner is never a problem, since most members of the species bear both male and female sex organs and fertilize themselves. Around 40 percent of its genes are closely related to ours.

ROBERT WATERSTON headed the U.S. team at Washington University in St. Louis.


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By comparing worm and human sequence, scientists can identify the related genes, and then use the worm to examine their function. From these studies conclusions can be drawn about genetic causes of disease and disorders. "Now that we have a better understanding of how an animal is built we can get some way closer to knowing how the human body works in health and disease," says John Sulston, director of the Sanger Centre at the Wellcome Trust Genome Campus, Cambridgeshire, England.

The sequencing project, was carried out by teams headed by Sulston at Sanger and Robert Waterston of Washington University nearly a decade ago but only really got rolling with sufficient funding in 1993. The two groups snipped and sequenced millions of bits of worm DNA, pasted it into long stretches of documented sequence, and added it to a public database. In recent years, a few dozen sequencing machines ran around the clock. In all, two million "reads" spelled out the worm sequence, 500 bases at a time. "We have provided biologists with a powerful new tool to experiment with and learn how genomes function," says Waterston.

Indeed, the successful completion of a blueprint for C. elegans is helping along the Human Genome Project, which recently announced it would speed up its effort to complete the enormous recipe for a complete person two years ahead of schedule. "Now we are more eager than ever to get the instruction book for a human being," says Francis Collins, director of the National Human Genome Research Institute, a lead player in the Human Genome Project.

Meanwhile, the worm sequencer results are already providing valuable clues to researchers. According to the report on the effort, which was published in the December 11 issue of Science, analysis of the worm's genome revealed 19,099 protein-coding genes--about one every 5,000 DNA bases--and 800 or so genes that have other functions. That's several times the number of genes predicted by classical genetics experiments. While 40 percent of genes match those of other organisms, including humans, the other 60 percent represent new mysteries awaiting explanation.

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