JOINT GENOME INSTITUTE SEQUENCES 15 ORGANISMS IN ONE MONTH

BERKELEY, CA-During the month of October, high-quality draft sequences of 15 bacterial genomes were produced at the U.S. Department of Energy's Joint Genome Institute (JGI) in Walnut Creek, California—a rate of better than one genome for every one and a half working days.

"This is a huge amount of data, a really diverse set of organisms, and a new approach to sequencing microbes," says Trevor Hawkins, deputy director of JGI and director of the Genomics Division at DOE's Lawrence Berkeley National Laboratory. Noting that only two dozen complete bacterial genome sequences have been published so far, Hawkins says that "by taking a sequence not to completion but to a high-quality draft representing more than 95 percent of the sequence, we can make essential data immediately accessible to biologists."

The Joint Genome Institute is a consortium formed by the Department of Energy's Lawrence Berkeley, Lawrence Livermore, and Los Alamos National Laboratories and expanded to include partnerships with Oak Ridge, Pacific Northwest, and Brookhaven National Laboratories, and Stanford University.

In addition to their value in basic research, many of the 15 bacteria whose draft sequences were produced during JGI's first Microbial Month have immediate implications for the economy and the environment. Among the sequenced organisms was Xylella fastidiosa, for example, a pathogen carried by sharpshooter insects that infects grapevines, citrus and almond trees, oleander bushes—which are used as median strips on California highways—and other important plants.

In collaboration with Alexander Purcell of the University of California at Berkeley, JGI researchers sequenced the two X. fastidiosa strains that cause almond leaf scorch and oleander leaf scorch. JGI researchers are also working closely with a consortium of the Organization for Nucleotide Sequencing and Analysis in Sao Paolo, Brazil, who earlier this year published the complete sequence of the X. fastidiosa strain that damages citrus, and who are now sequencing the strain that swiftly kills grapevines.

"With Xylella, JGI is not duplicating the efforts of the Brazilian researchers but is collaborating with them to put a swift end to these devastating diseases," says Patrick Gleeson, executive director of the American Vineyard Foundation. "The efforts of the JGI in sequencing these microbes will move the scientific learning curve exponentially forward, not only through the effectiveness of the sequences themselves but because they will be made publicly available and can be accessed by
scientists internationally."

Another intriguing organism sequenced during Microbial Month was Magnetospirillum magnetotacticum, "Nature's compass," a microbe that precipitates crystals of magnetite and incorporates them in chains of magnetosomes that it uses to sense the Earth's magnetic field.

JGI researchers collaborated with Mel Simon of the California Institute of Technology on M. magnetotacticum, which Caltech geobiologist Joseph Kirschvink believes is the best candidate for the ancestor of all mechanisms of biomineralization on Earth, including the ability to form bones and teeth. To Kirschvink, the extraordinary similarity of the organism's magnetic structures to magnetic particles found in the ancient Martian meteorite ALH84001 "argues that the genes which control magnetite biomineralization may well be of Martian origin."

The decision to sequence more than a dozen diverse organisms in a single month came after JGI completed working-draft sequences of human chromosomes 5, 16, and 19 in April of this year and then, just three weeks later, completed a working draft of the "supergerm" Enterococcus faecium in a single day.

"A typical bacterial genome is less than 10 million bases," says Paul Predki, JGI's associate director for production genomics and a member of Berkeley Lab's Genomics Division. "Our automated facilities easily handle 2 million bases a day."

Predki explains that the high-quality microbial draft sequences are about "eight deep," the average number of overlaps among short, "shotgunned" pieces of the organism's DNA. "Although there are gaps, the draft sequences are still exceedingly useful."

In the past, Predki says, researchers who may have worked years sequencing a genome were understandably reluctant to publish before it was complete. "But microbial genomes are only on our sequencers for a day or two and in our facility for a few weeks. With such a small time investment, there is no motivation to hold back."

Information produced at JGI is immediately sent to Oak Ridge National Laboratory's 'annotation pipeline,' where the sequence is rapidly searched for genes and other features. Frank Larimer, senior scientist in computational biology at Oak Ridge, coordinates the automated annotation of microbial genomes.

"The collection of organisms represented expands the sample of major phylogenetic groups sequenced and provides deeper sampling of select species," Larimer says. "Providing users with annotation of high-quality draft sequence will facilitate deeper understanding of the evolutionary relationships as well as accelerate data-mining of these genomes for specific research needs."

"Our intent has been to produce and release draft sequence and annotation to the public with unprecedented speed," Paul Predki says, and adds, "We've succeeded."

The draft bacterial genome sequences are openly available on the "Genome Portal," the new JGI website being developed by associate director for computational genomics Daniel Rokhsar, a member of the Physical Biosciences Division at Berkeley Lab, and by JGI bioinformatics team leader Tom Slezak of Lawrence Livermore National Laboratory.

Rokhsar hopes the Genome Portal will soon become a web home for all the sequenced organisms. "Some users want raw sequence, some may want a list of genes, some want to locate genes that might be responsible for certain traits. Some want to ask open-ended questions that might span many genomes. We want to provide whatever the user wants."

To get maximum benefit from the entire set of bacterial genomes, JGI plans to convene the principal biological researchers as soon as possible. "Each organism has a champion, an expert in the biology of that organism," Rokhsar says. "By comparing the genomes of many different organisms at once, we can achieve unique perspectives."

The successful conclusion of the first of JGI's Microbial Months lends urgency to the next two, already scheduled for March and August, 2001. Although the organisms to be sequenced have yet to be chosen, Predki believes that researchers will be so excited by the results of the first Microbial Month that they will be eager to nominate their own favorite bugs. "We're planning on working with the community."

See the latest sequencing information from JGI's inaugural Microbial Month.

By using high-throughput genomic technologies and computational methods and by leveraging the unique capabilities of DOE's national laboratory system, the JGI is discovering and characterizing basic principles underlying the organization, function, and evolution of living systems—yielding new understanding that can be addressed to the DOE's key missions in energy, the environment, and human health.

The Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California.

Contact information:

Dr. Paul Predki can be reached at (925) 296-5635 or by email at pfpredki@lbl.gov.

Dr. Trevor Hawkins can be reached at (925) 296-5682 or by email at tlhawkins@lbl.gov.

Dr. Daniel Rokhsar can be reached at (925) 296-5852 or by email at dsrokhsar@lbl.gov.

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