Group Unveils Worm's Complete Genetic Blueprint

December 10 marked another "major milestone" in molecular biology. An international consortium of scientists announced that they have obtained the first complete genetic blueprint of a complex animal. C. elegans Researchers from Washington University in St. Louis and the Sanger Centre in Cambridge, U.K., have sequenced the 97 million-base genome of Caenorhabditis elegans, biologists' favorite worm. The product of a nine-year effort, the C. elegans sequence joins those of E. coli and yeast in what Francis Collins, director of the National Human Genome Research Institute in Bethesda, Md., describes as "a string of stunning successes in determining the complete sequences of ever-more-complex organisms." "This sequence gives us our first real picture of what it will be like to understand a complex, multicellular organism such as ourselves," says National Institutes of Health Director Harold Varmus. With greater than 99 percent of the worm sequence complete, the researchers have uncovered 19,099 protein-coding genes (compared to 6,217 found in yeast and some 80,000 predicted for humans). Their results appear in the Dec. 11 issue of Science.1 Having the worm sequence in hand (or on the Web) means that researchers around the world can now begin to examine how genes work and interact to build a creature that digests food, responds to touch, and reproduces sexually. "It's an incredible human accomplishment--like landing on the moon," says Bob Horvitz, a Howard Hughes Medical Institute investigator at the Massachusetts Institute of Technology. "Actually, it's better than landing on the moon because it's immediately useful in a practical way." Physicians and physiologists alike will turn to the worm sequence to help them identify and characterize the genes involved in human biology and disease. Nearly 75 percent of human genes have some counterpart in the C. elegans, and more than half of the genes involved in disease are related to worm genes, including genes involved in cancer, diabetes, and Alzheimer's disease. "This knowledge will have a profound impact on the discovery of new medicines," predicts Horvitz. The sequence may already be yielding interesting information about the evolution of genes. Although genes appear to be distributed evenly along the six pairs of C. elegans' chromosomes, highly repeated sequences tend to cluster at the ends. "We think those regions might be gene nurseries or gene graveyards--a place where genes are being formed or being lost," says Bob Waterston, who led the St. Louis team.2 Waterston thinks the important genes are protected in the middle, and that the chromosome ends may be where nature is free to experiment--and where genes are forming and being lost at a high rate. Completing the worm sequence also bodes well for other sequencing projects, from mouse to human. "The success of this enterprise predicts success for the human sequence," notes Collins, while thoughtfully chewing on one of the complimentary Gummi worms that littered the conference table. But for now, the researchers intend to work toward obtaining the last difficult bits of the worm sequence. "We want to join the remaining gaps so we can assure ourselves that we're not missing anything," says John Sulston, the leader of the Sanger team. Then they'll move beyond the sequence to the biology. "We're not done; we'll never be done," says Sulston. "We'll just go on deepening and broadening our understanding, making C. elegans a richer biological tool for the scientific community." Karen Hopkin is a freelance science writer based in Silver Spring, Md. See multiple articles in the special section, " C. elegans: Sequence to Biology," Science, 282:2011-46, Dec. 11, 1998. R. Lewis, "Comparative Genomics Reveals The Interrelatedness Of Life," The Scientist, 12[1]:11, Jan. 5, 1998.

Group Unveils Worm's Complete Genetic Blueprint

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