October 26, 2000

 

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BERKELEY, CA ó Scientists searching the human genome data for genes and the DNA sequences that control their activity will soon have a valuable new resource courtesy of the Japanese delicacy known as Fugu (Fugu rubripes), the puffer fish. An international consortium, led by researchers at the Joint Genome Institute (JGI) of the U.S. Department of Energy (DOE), has announced a collaborative agreement to sequence the Fugu genome. Although the Fugu genome contains essentially the same genes and regulatory sequences as the human genome, it carries those genes and regulatory sequences in approximately 400 million bases as compared to the three billion bases that make up human DNA. With far less so-called "junk" DNA to sort through, finding genes and controlling sequences in the Fugu genome should be a much easier task. The information can then be used to help identify these same elements in the human genome.

FUGU RUBRIPES, ALSO KNOWN AS A PUFFER FISH OR BLOWFISH

Said Energy Secretary Bill Richardson, "This genetic information from a distantly related vertebrate will help us read the book of human life with new understanding and knowledge. Given the major contributions already made to the human genome project by the Energy Department's Joint Genome Institute and their tremendous capability to decode DNA, this new effort is a logical and exciting next step in the project."

DOE began the Human Genome Project in 1986 out of its Congressional mandate to study the genetic and health effects of radiation and chemical by-products of energy production.

Said Trevor Hawkins, deputy director of the JGI, "This project will represent our single largest genome sequencing project to date and be the centerpiece of our new Genome Portal."

Based in Walnut Creek, California, the JGI is one of the largest publicly funded genome sequencing centers in the world. The institute is itself a consortium initially formed by three DOE national laboratories, Lawrence Berkeley, Lawrence Livermore, and Los Alamos. Joining the JGI in this collaborative effort to sequence the Fugu genome are the Institute for Molecular and Cell Biology (IMCB) which is in Singapore and is led by Chris Tan; the MRC UK HGMP Resource Centre, which is in Cambridge and whose role in the sequencing of the Fugu genome will be led by Greg Elgar; The Molecular Sciences Institute, which is located in Berkeley and is led by Sydney Brenner who is also a Visiting Investigator at the IMCB; and the Institute for Systems Biology, which is located in Seattle and led by Lee Hood.

Evolution has conserved many of the DNA sequences used in genes to code for proteins or in the elements that regulate gene expression. This makes comparisons of genome sequences between species an effective and efficient means of finding new genes. Currently, the favorite genome models for gene hunters include those of the mouse, fruit fly, yeast, and nematode. Fugu is a wildly popular food in Japan even though it can be lethally poisonous if prepared improperly. The genome of this fish, with its 8-fold compactness compared to the human genome, should make it a very cost-effective model.

Explains Daniel Rokhsar, JGIís associate director for computational genomics, "Within each taxonomic grouping, there can be wide variations in genome size that are not necessarily related to the complexity of the organism. These variations appear to be due to differing amounts of 'junk' or 'selfish' DNA, often dominated by the remains of ancient viral-like genomic infections that left hundreds of thousands of repetitive elements littered throughout the genome. The Fugu genome seems to have avoided these events and sequencing it will therefore allow us to obtain a complete vertebrate genome extremely rapidly."

Under the terms of the consortiumís agreement, the JGI will be responsible for both the production of draft sequences as well the computational aspects of the project. The Fugu genome will be sequenced following the same "shotgun strategy" used so successfully by JGI researchers to complete the draft sequences of human chromosomes 5, 16 and 19. To speed the process even faster for the Fugu genome, researchers will use customized software now being developed at the JGI under the direction of Rokhsar. JGI scientists anticipate having more than 95-percent of the Fugu genome sequence available in an accessible database by March 2001.

The other members of the consortium will be responsible for the finishing phase of the project as well as contributing to the computational analysis of the genomic data. The long-term goal of this consortium is to generate complete sequence coverage of the Fugu genome and assemble it into a finished form for comparative genomic analysis.

Nobel laureate James Watson, co-discoverer of DNA's double helix structure, has endorsed this project. "The Fugu fish sequence, in combination with the draft mouse genome, to be available in early 2001, will greatly add to the comparative sequence studies that are now required to isolate coding and non-coding conserved elements within the human genome."

Said Sydney Brenner, whose pioneering studies of Fugu biology with Greg Elgar and his colleagues in Singapore helped show that the organization of Fugu genes parallels that of human genes, "I am delighted that DOE has decided to sequence Fugu. The data will greatly enhance the identification of gene promoter regions and lead to a much better understanding of the human genome."

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