 
UC
Berkeley collaboration with Celera Genomics concludes with publication
of nearly complete sequence of the genome of the fruit fly
24
Mar 2000
By
Robert Sanders, Public Affairs
BERKELEY
-- In a unique collaboration between industry and university
scientists, researchers this week reported the complete sequence
of nearly all the genes on all the chromosomes of the fruit
fly, Drosophila melanogaster.
The
feat, achieved in record time with new techniques pioneered
by Celera Genomics Corp. of Rockville, Md., is reported in three
articles in this week's issue of Science magazine by Celera
and the Berkeley Drosophila Genome Project (BDGP), based at
the University of California, Berkeley, and Lawrence Berkeley
National Laboratory. The BDGP, directed by Gerry Rubin, professor
of genetics in the College of Letters & Science, teamed
up with Celera last February in an attempt to speed up sequencing
of the fruit fly genome.
"This
should accelerate things quite a lot, allowing us to finish
in a year rather than another three years, which was the original
plan," Rubin said last year. The scientists met their goal,
depositing most of the sequence of the fruit fly genome in a
public database, GenBank, by the end of last year, for use free
of charge by researchers around the world.
The
sequencing of the fruit fly genome is an important milestone
on the road to sequencing the entire human genome, Rubin said.
"Because
the fruit fly is more similar to humans than any other animal
sequenced so far, its genetic information can be directly related
to humans in many cases," he said. As one of the most popular
research animals for geneticists, he added, "the animal
has provided an extraordinarily deep and broad understanding
of the function of genes in disease."
Principal
authors of the papers are Rubin and Suzanna Lewis, leader of
the informatics group in the BDGP; Sue Celniker, leader of the
LBNL team; and Mark D. Adams, PhD, vice president, genome programs;
Eugene Myers, PhD, vice president, informatics research, and
J. Craig Venter, PhD, president and chief scientific officer
of Celera.
The
Science papers, one with 192 authors, outline the sequencing,
assembly and analysis of the fruit fly genome, which the scientists
declare is "substantially complete." Celera estimates
that the sequences published today containing the fruit fly's
genetic information have an accuracy of greater than 99.99 percent.
The first insect and the largest organism sequenced to date
with 120 million base pairs, the fruit fly is also the first
organism with a central nervous system to be sequenced.
"This
unique collaboration between Celera and the publicly funded
researchers at BDGP has been one of the most successful academic
collaborations that I have been involved in during my 30-year
scientific career. It should serve as a model for future collaborations,"
Rubin said. "We now have a complete Drosophila genome 18
months sooner and millions of dollars cheaper than anyone expected."
Rubin
said that because of this cost and time savings, researchers
could now move forward sooner in delving deeper into the fly
genome, possibly uncovering the functions of many of the genes.
Using
a technique called "whole-genome shotgun sequencing,"
the team at Celera and BDGP identified 13,601 genes on the four
chromosomes of the fly. The accuracy and degree of completeness
was confirmed by analysis using data supplied by BGDP. Of the
289 genes known to cause diseases in humans, researchers discovered
about 175 of them in Drosophila melanogaster. These genes cover
a wide range of diseases including cancer, neurological and
cardiovascular disorders, and malformation syndromes.
"One
of the advantages of the whole-genome shotgun technique in sequencing
genomes is that gene discovery is an immediate by-product,"
said Celera's Mark Adams. "The discovery of approximately
60 percent of the genes known to cause human disease is an example
of how Drosophila research and the whole shotgun sequencing
technique can speed gene discovery and could aid researchers
in more efficient and cost effective drug development."
One
article published this week in Science compares the genomes
of three organisms sequenced to date: the fruit fly, the roundworm
Caenorhabditis elegans and common bakers yeast, Saccharomyces
cerevisiae.
That
paper, authored principally by Lewis and Rubin of UC Berkeley,
notes that the worm and fruit fly have very nearly the same
number of proteins, despite the evolutionary gap between them.
The number is only twice that of yeast, which is even more removed
from the others.
"This
is perhaps counterintuitive, because the fly, a multicellular
animal with specialized cell types, complex development and
a sophisticated nervous system looks more than twice as complicated
as single-celled yeast," the researchers write. "The
lesson is that the complexity apparent in the metazoans (multicellular
animals) is not achieved by sheer number of genes."
Rather,
they say, animals got more complex by using existing proteins
in new ways, including segregating proteins in different places
and using them at different times to achieve a new function.
The
new fruit fly genome sequences are bound to help scientists
attack problems of human disease and development much more effectively,
and open new areas of research, they conclude.
"The
availability of the annotated sequence of the Drosophila genome
enhances the fly's usefulness as an experimental organism,"
they wrote, adding, "the relative simplicity and manipulability
of the fly genome means that we can address some of these biological
questions much more readily than in vertebrates."
The
fruit fly has been an important animal in genetics studies for
most of this century, since Thomas Hunt Morgan chose it for
study in 1910. Genetic experiments in the fly have revealed
many important features, including the signals - those, for
example, that make the head form at one end of the body and
the tail at the other - that establish body regions. Genes that
control organization of the fly's body also have counterparts
in humans and can help explain developmental problems that result
in birth defects.
The
fruit fly sequencing project was first funded in 1992 by the
Human Genome Project, with UC Berkeley as the base of operations
and Rubin as head of a consortium of universities and federal
labs. The plan was to sequence the fruit fly's 150 million base-pair
genome by 2001. By the time BDGP teamed up with Celera, researchers
at UC Berkeley had already produced about 20 percent of the
fly's DNA sequence in high-quality form.
Researchers
at Celera, a business unit of The Perkin-Elmer Corporation,
employed their shotgun sequencing strategy to attack the fruit
fly genome. The whole-genome shotgun method produces sequences
from many small, random DNA fragments, using high-throughput
machines. By combining sequences with map information and additional
sequences provided by the UC Berkeley group, the team assembled
the data into long stretches of correctly ordered, continuous
genomic sequence.
To
date Venter has wielded the whole-genome shotgun method to sequence
the much smaller genomes of nearly a dozen bacteria, including
Hemophilus influenzae, the cause of various respiratory and
neurologic infections. Celera is now hard at work on the much
larger human genome.
"This
is an exciting day for Celera. Not only has the whole genome
shotgun technique been proven in the very large and complicated
Drosophila genome, but we have done it in the context of an
extremely successful collaboration with Dr. Rubin and researchers
at the Berkeley Drosophila Genome Project and Baylor University,"
said Dr. Venter. "This bodes well for our ability to assemble
the human genome."
The
BDGP is a consortium of research groups working at UC Berkeley,
Lawrence Berkeley National Laboratory, Baylor College of Medicine
and Carnegie Institution of Washington. It is funded by the
National Institutes of Health, the Department of Energy and
the Howard Hughes Medical Institute.
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