Feb. 22, 1999
Volume 51, No. 21
Worm's gene map a boon to study of human genetics
Announcing one of biology's most significant finds, the journal Science devoted a special December issue to exploring the ramifications of the recently acquired complete genetic sequence of C. elegans, a small soil worm. To the layperson, such a discovery may seem insignificant, but researchers Guy Benian and Steve L'Hernault remain certain this discovery will have greater impact than suspected.
"Basically, you can think of a genome sequence as the blueprint for life, and the significance of this work is that the blueprint for a multicellular organism is now available," said L'Hernault. Unlike bacteria and yeast, the worm is composed of a collection of cells, just like a human. An associate professor in biology, L'Hernault uses C. elegans to understand from a genetic perspective how cells divide and become different. This query has led him to focus on two fundamental issues of a multicellular creature: the formation of tissue and cell-to-cell recognition.
His attraction towards C. elegans as a research model closely parallels that of his colleague, Benian, assistant professor of pathology and cell biology. "I decided to take advantage of the simplicity of the worm genome," Benian said. "When I say simplicity, that compares to the human genome or mouse genome, where there's a lot of what's called 'junk.' The worm genome is a lot more efficient; from the complete sequence we know there's only about 25 percent of it that doesn't encode for anything."
The term genome refers to the entire DNA sequence of a particular organism. Within this sequence, the particular sections that serve as cellular templates are called genes. However, long stretches often referred to as "junk DNA" separate these genes, and some junk DNA may lie within the gene sequence itself. The complexity of mapping genomes can best be understood through an imperfect analogy: imagine the difficulty of reading a weighty novel like Ulysses if it were written in an unknown language and the words were always separated by multiple paragraphs of meaningless gibberish. But while the difficulty of this task may seem mindboggling, the C. elegans genome is fairly user-friendly compared to more cryptic genomes like those of humans-the human genome is more than 90 percent junk sequence.
Benian researches the various cellular structures that make up both muscle and the skeleton of cells. He does this by studying worms with mutations in genes that encode for these structures. By examining these structures he discovered twitchin, a giant architectural protein with unexpected membership in a protein family involved in immune response. Currently Benian is analyzing the function of a several "unc" genes, so called because mutations in these genes cause worms to move in an uncoordinated manner. He has found that the unc-60 gene encodes for two proteins: one involved in muscle formation and the other in early embryonic development.
However, before researchers can study a gene, they first need worms with mutations, and finding these worms and the exact location of the mutation is a trying task. "Historically, it was a very arduous process that took years," said L'Hernault. Now this has all changed. The complete sequence of C. elegans is located on the web, and it has been annotated. "What used to cost lots of money now costs nothing. It frees up your time to concentrate on more interesting aspects of the biology rather than collecting the DNA sequence and locating genes which until recently were a very major part of what these labs did."
Both researchers have already seen a payoff from the availability of this information. L'Hernault has noticed several new sperm genes and plans to investigate their function in cell recognition. "The ultimate cell recognition problem is the sperm recognizing the egg," he said.
However, both scientists emphasize the broader implications of the recent discovery: it has been a proving ground for the both the hardware and the software involved in sequencing the human genome. The Human Genome project lies at the apex of America's multimillion-dollar investment in science. When completed, humans will have a complete blueprint of the genes defining our species. But until the human sequence is known, much can be learned from this tiny worm because now science will no longer be looking at genes in isolation.
"For the first time, we have an entire genome and we can study entire gene families," said Benian. "We can't do that with any other multicellular organism."