Scientists report on the sequenced fruit fly genome

Lori Stiles
March 23, 2000

Boris Dunkov, University of Arizona, 520-6213046,
Gene Myers, Celera Genomics Corp., 240-453-3007,

A team of almost 200 scientists reports tomorrow in Science how they have essentially completed sequencing the whole genome of the Drosophila fruit fly..

The feat lays the foundation for a new era in genetics research, they report. Scientists will no longer have to spend time searching for genes. They will be asking what the genes do.

And it demonstrates that the controversial whole-genome "shotgun" sequencing technique can be used successfully to sequence larger genomes _ including the human genome, they add.

The team of authors comprises scientists from Celera Genomics Corp. of Rockwell, Md., the Berkeley and European Drosophila Research Projects, and a few dozen scientists from around the world who are experts in various areas of fly research, including the University of Arizona's Boris Dunkov.

Gene Myers, Vice President for Informatics Research at Celera and an author on the Science paper, is a UA professor of computer science on leave from the university. (See the Jan. 13, 1999 news release, "UA computer scientist joins venture to 'shotgun' sequence human genome." The story is online at the UA News Services science and research website, )

A genome is all of the genetic material, or hereditary information, in an organism. Geneticists have studied fruit flies for nearly a century. Twenty years ago, scientists begun using recombinant DNA cloning and sequencing techniques to identify particular genes and map their location in the fly genome.. The federally funded Human Genome Project in 1990 selected Drosophila as a model organism for study, giving rise to several genome projects in the U.S., Europe and Canada.

The Berkeley Drosophila Genome Project group had sequenced about a fifth of the fruit fly genome using recombinant DNA cloning methods when, in January 1999, it joined with Celera in the effort to sequence the entire fly genome..

Celera is pioneering the whole-genome shotgun sequencing strategy. This technique randomly breaks apart all the DNA of an organism, sequences the fragments, then reassembles the pieces in overlapping sequences to reconstruct the complete genome sequence. The method bypasses the time-consuming gene-mapping step in the traditional gene sequencing method.

Berkeley collaborators supplied the extensive clone-based sequence and other supporting data in their joint fly genome project with Celera. In September 1999, Celera and Berkeley scientists announced they had sequenced the fly genome that encodes some 13,600 genes in 1.8 billion base pairs of DNA.

In November, a month before releasing all the sequence data in GenBank, Celera and the Berkeley group invited 40 scientists from the international fly research community to take a first look at the sequenced Drosophila genome.

Boris Dunkov was among those invited to Celera for the 2-week "Annotation Jamboree."

"When I got a first look at the sequenced fly genome, it was amazing," Dunkov said. "I was overwhelmed with the amount of information that, suddenly, was there."

Dunkov is an insect biochemist who has worked with Drosophila in studying iron metabolism and cytochrome P450 enzymes, a large family of enzymes that play a major role in the insect's life. These enzymes are important in the synthesis and/or degradation of hormones and pheromones, and in the metabolism of natural and synthetic toxicants, including insecticides.

The jamboree was a first-cut exercise for Drosophila experts to work on the initial "annotation" of the assembled fly genome, Dunkov said.

The scientists were asked to organize and interpret the gene set for a given protein family or biological process -- in Dunkov's case, the fly's cytochrome P450 enzymes and iron-binding proteins. They worked to define genes, to classify them according to predicted function, and to understand how it all fit in the whole-genome picture.

Even with computer gene-finding tools and the efforts of the large community of Drosophila researchers, annotating the entire fly genome "will take years," Dunkov noted. To annotate the entire genome involves discovering all the proteins which are encoded by the genome and learning how proteins function as the fly develops and lives its life.

"But the availability of the annotated fruit fly genome sequence will change the way we do research in biochemistry and physiology of other insects -- economically and medically important insects," Dunkov said.

Drosophila is the champion biological model for studying agriculturally important insect pests and insects which, as vectors of diseases like malaria and dengue fever, kill millions of people annually. Dunkov also works with mosquitoes as vectors of disease. He predicts a boom in new insect genome projects focused on insects of agricultural and medical importance.

The fruit fly is one of the best studied and genetically understood of all organisms, notes Regents Professor Margaret G. Kidwell of the University of Arizona. She is an evolutionary geneticist who has been studying mobile genetic elements, or "transposons," for more than 25 years, specializing in those found in Drosophila fruit flies. (See the Feb. 21, 2000, news release "Mobile Elements, Evolution and Human Disease." The story is online at the UA News Services science and research website, )

"I think this is a pretty important achievement," Kidwell said. "The shotgun approach has been remarkably successful, despite many earlier doubts. And looking ahead, it promises well for the on-going human genome sequencing effort.

"The sequencing of the Drosophila genome represents the successful completion of one more important step in place to first sequence the relatively small genomes of important experimental organisms _ bacteria, yeast, flies and worms _ before attacking the considerably larger human genome," Kidwell said. "The smaller genomes are biologically interesting in their own right as well as serving as pilot projects to refine the tools for automated sequencing and computational analysis of the human genome."

In the past few years, human geneticists have realized just how important the Drosophila genome is for understanding the human genome and human disease.. They have discovered striking "homologies," or sequence similarities, between fly and human genes. They have discovered that whole pathways of developmental and cellular processes in flies are maintained in humans, using the same molecules.

Celera is using the shotgun strategy to sequence the 3.5 billion base pairs in the human genome, a project that will be finished by the end of the year, according to senior company executives.

Unfortunately, a public/private arrangement that worked well in sequencing the Drosophila genome may not work in sequencing the human genome. At this point, public and private human genome project directors are contesting who will control the raw data.


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