Sequencing of pufferfish will help JGI efforts to solve mysteries of human genome

The recent sequencing of the Japanese pufferfish Fugu rubripes provides a plethora of information that will help researchers master the ins and outs embedded in the human genome.

An international research consortium — which was led by the U.S. Department of Energy’s Joint Genome Institute and the Singapore Biomedical Research Council’s Institute for Molecular and Cell Biology — announced the completion of the Fugu genome at last week’s 13th International Genome Sequencing and Analysis Conference in San Diego. Other members of the consortium are MRC UK Human Genome Mapping Resource Centre, the Cambridge University Department of Oncology, the Institute for Systems Biology, and private industry companies, Celera Genomics and Myriad Genetics, Inc.

The Fugu genome contains essentially the same genes and regulatory sequences as the human genome, though it carries those genes and regulatory sequences in approximately 365 million bases, compared to the 3 billion bases that make up human DNA. During the past year, nearly 4 million pieces of Fugu genome sequence were identified by the consortium. The genomic fragments overlap each other, allowing them to be reassembled computationally to reconstruct long stretches of the Fugu genome. The Fugu genome is the first vertebrate genome to be draft sequenced after human.

There are more than 100 species of pufferfish that live in saltwater and fresh-water habitats. Fugu species are farmed in Japan and the flesh is consumed as a delicacy, though certain organs of the fish must be avoided because they contain a potent neurotoxin causing those who eat the organs to die, sometimes in minutes. About 60 percent of puffer poisonings prove fatal.

The mapping of Fugu is significant because its compact form and similarity to the human genome make it an important tool for getting at the information encoded in the human sequence, according to Trevor Hawkins, JGI director. With the basic gene-level description of two vertebrates, researchers can more easily compare and contrast them to discover new human genes and elements, which control or regulate the activity of genes.

"Although the Fugu genome is only one-eighth the size of our human genome, it has a similar compliment of genes," Hawkins said. "However, we don’t know all that much about the structure of those genes and how they are turned on and off. By sequencing the genomes of microbes, sea squirts and Fugu, we can find links to understanding the biology of the human genome."

Fugu and humans are related by evolution. About 450 to 500 million years ago the first vertebrates appeared in the early oceans. Their descendents split into two main groups: the ray-finned fish — which include Fugu and most common fish — and the lobe-finned fish, a more obscure group. During millions of years, the lobe-fins evolved into the limbs possessed by all four-limbed creatures, including reptiles, amphibians, birds and mammals.

"So the Fugu is a very distant cousin," Hawkins said. "And consequently, this common ancestry is still recorded in our genes. That’s why this sequencing is so incredibly important to us."

Fugu is the first animal genome to be sequenced and assembled in the public sector using the "whole genome shotgun" sequencing approach.

"We first chopped the genome up into pieces that are small enough to sequence," said Dan Rokhsar, associate director for computational genomics at JGI. "The challenge was then to reassemble the genome by putting together nearly four million of these overlapping fragments in the same way that you’d put together a giant jigsaw puzzle."

The JGI is one of the largest publicly funded genome sequencing centers in the world and is operated jointly by the three UC-managed DOE national laboratories, Lawrence Livermore, Lawrence Berkeley and Los Alamos.

The consortium plans to publish an initial analysis of the draft Fugu genome in early 2002.

For more information and up-to-date Fugu sequence information, go to http://www.jgi. doe.gov/programs/fugu.htm .