'A leap' in quest to map out DNA

Genetic blueprinting of fruit fly raises researchers' hope

100-year gene search ends

February 19, 2000|By Douglas Birch | Douglas Birch,SUN STAFF

WASHINGTON -- Scientists using an unorthodox approach have created the first genetic blueprint of the fruit fly, an achievement that could pave the way for completion of a blueprint of human DNA by this summer.

Teams at Celera Genomics in Rockville and the University of California at Berkeley said yesterday they have discovered nearly all the important DNA of the tiny insect, work that could lead to new insights into everything from learning and memory to aging and cancer.

Drafting of the blueprint also marks the end of a century-long hunt for all the fly's genes, launched by Thomas Hunt Morgan, one of the founders of modern genetics. Today, the fly, Drosophila melanogaster, is still one of the most important lab tools for uncovering how genes influence the structure and behavior of organisms.

While the fly's sequence has not been fully read, researchers said they have found 13,601 genes -- more than 99 percent of those scattered through the fly's DNA. Those genes contain almost all the instructions the insect needs to grow, survive and reproduce.

"The most important information is there," said Edward Lewis of the California Institute of Technology, commenting on the achievement. "This is a really big leap."

About half the fly's genes are thought to be similar to human genes, including those implicated in diabetes, Alzheimer's, Lou Gehrig's disease and many types of cancer.

Mark D. Adams, a Celera scientist, said researchers last fall pored over a draft of the fly's genetic blueprint -- its genome -- and found a gene similar to the p53 gene in humans. The p53 gene corrects errors during the replication of DNA, an important mechanism for preventing cancers.

"It just jumped right out of the genome," he said.

Fly researchers had previously discovered a gene called "Methuselah" that increases the life span of flies by 35 percent. Looking at the fly's genetic blueprint, Adams said, scientists found that Methuselah was only one of a family of 11 similar genes. Understanding how genes control aging could help humans cope with getting older.

As of yesterday, there were still 1,600 gaps -- missing segments of genetic information -- in the fly's functional DNA. Berkeley scientists hope to reduce the number to fewer than 100.

Scientists at Celera and Berkeley did not try to read about 60 million of the 180 million chemical units in the fly's genome. But scientists still consider the blueprint close to complete. The missing units are from the fly's so-called "junk" DNA, which contains no genes.

The Celera-Berkeley group used a radical "shotgun" approach to reading the order, or sequence, of chemical units in large segments of DNA. Gerald Rubin, the leader of the Berkeley team, said the group's success proves critics wrong.

Using the shotgun, Celera researchers shattered the genetic material and put the pieces back together with the aid of computers. Scientists working with the international Human Genome Project, led in this country by the National Institutes of Health, take a more methodical approach -- dis-assembling the DNA piece by piece.

The shotgun method "worked better than any of the most optimistic predictions," said Rubin. "It has been a roaring success."

Celera's co-founder, J. Craig Venter, and Dr. Hamilton O. Smith, a Nobel Prize-winner and retired Johns Hopkins University professor, pioneered the shotgun method. They used it in 1995 to create the first complete genetic blueprint of a free-living organism.

Smith, who now works at Celera, also played a key role in the fruit fly effort.

By joining forces with Celera, Rubin said, Berkeley shaved 18 months off the time needed to complete the fly genome and saved the federal government several million dollars in grant money.

Celera, a company that hopes to profit from selling genetic information to drug firms, is racing against the publicly funded Human Genome Project to publish the first human genetic blueprint. For almost two years, both sides have talked about collaborating on the human genome, with little progress.

Yesterday, Venter said he hoped publication of the fly's genome would "help the human collaboration get off the ground."

Outside the scientific world, fruit flies are seen as pests. But Lewis, a former student of Thomas Hunt Morgan's, said the genetic blueprint will make the fly even more important to the study of human genetics than it has been for the past 100 years.

"It's easy to make fun of this, it's easy to laugh at the fly," says Lewis. "But it turns out that we're laughing last."

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