Puffer Fish's Lean Genome Is Sequenced
Anil Ananthaswamy

October 26, 2001; 1:10 PM; The genome of the poisonous Puffer Fish has been sequenced by an international consortium of researchers. Comparison with the "clean" DNA of the fish will help scientists pick out human genes from the background "junk." The human genome was sequenced earlier this year. Researchers have since been sifting through the three billion units of information to identify the genes, their structure and functions. But it is an arduous task because so much of the genome is "junk" DNA, which does not code for proteins.

So researchers are turning to the genomes of related vertebrates such as the puffer fish or the mouse to better understand the human counterpart. And the puffer fish Fugu rubripes is a prime candidate. "The gene complement within Fugu looks to be very similar to the gene complement known right now within humans," says Trevor Hawkins, consortium team member and Director of the Joint Genome Institute (JGI) in Walnut Creek, CA.

Crucially, the fish uses only 350 million base pairs to code for the genes, lacking most of the junk DNA in the human genome. JGI's Dan Rokhsar says, "It's almost like the human genome written in shorthand." Given the compact Fugu genome, identifying genes and the DNA sequences that regulate these genes should be much easier. Armed with that data, researchers can extract related parts from the human genome. "In terms of the human genome project, having the Fugu genome is going to be one of the real landmarks in linking the genome to genes to proteins all the way up to molecular medicine," says Hawkins.

George Weinstock, Co-director of the Baylor College of Medicine's Human Genome Sequencing Center in Houston, Texas, agrees: "This allows us to ferret more and more from the human genome in terms of the important sequences that are there." "This is the very, very beginning of what is going to become the dominant theme in genomics in the next few years," he says.

Shotgun Sequence

To sequence the Fugu genome, researchers in the US, England, and Singapore used a technique called the whole genome shotgun sequencing. They chopped up the Fugu genome into small pieces, decoded each one, and then used sophisticated computer software to piece together the fragments." So far, they have identified nearly 90 percent of the Fugu genome," says Hawkins.

A similar method was used by Celera Genomics of Rockville, Maryland, to sequence the human genome. But they had access to public information that identified certain sequences of DNA as landmarks on the genome that could be used to assemble the fragments. However, the Fugu consortium assembled the shot-gunned DNA sequences without any such landmarks. "This is quite a significant step forward," said Hawkins.

The consortium announced their results on Friday at the 13th International Genome Sequencing and Analysis Conference in San Diego, California. The sequencing of a second type of puffer fish, with a similarly compact genome, was announced at the same time. The Tetraodon nigroviridis was sequenced by Genoscope in Paris, FRANCE and the Whitehead Institute Center for Genome Research.

Pufferfish Genome Now Complete and Online
Lois Wingerson,
BioMedNet News

October 26, 2001; 16:45 EST - A large international consortium of geneticists today unveiled the complete sequence of the puffer fish Fugu rubripes . One of the world's smallest genomes, virtually free of so-called junk DNA, it promises to be highly valuable for elucidating the meaningful contents of the human genome - both because of what it contains and what it does not.

The Fugu genome is a landmark in several senses. It is the first vertebrate genome to be assembled fully by the whole-genome "shotgun sequencing" method, which does not involve gene mapping. It is also the first publicly available assembled vertebrate genome, according to Trevor Hawkins, who is director of the US Department of Energy's Joint Genome Institute (JGI), one of the partners in the effort.

"Up until now, the only facility where you could do this was Celera," Hawkins said. "We have a suite of tools now available to go on to develop other vertebrate genomes." The genome consortium is one of the largest of its kind to date, involving scientists from five institutions, three countries, and two private companies (Celera Genomics and Myriad Genetics). Both Celera and Myriad provided Fugu sequence data for validation.

The consortium released the sequence today - one year to the day after its own formation was announced - at the International Genome Sequencing and Analysis Conference in San Diego, California. The genome is now available online at websites operated by all three participating organizations.

"I had given up on ever getting to this stage," said the first and most vocal champion of this genome, Sydney Brenner of the Salk Institute for Biological Studies, who is well-known for promoting the worm Caenorhabditis elegans as a model organism. Brenner ran into Hawkins at a meeting in Berkeley, California, last year, and found him equally enthusiastic about the project. Brenner likes to call Fugu a "discount genome," because it contains essentially the same genes and regulatory sequences as the human genome in far less space - about 365 million bases, as compared to the 3 billion in the human version - but cost about six percent of the human genome project.

The puffer fish genome will be "indeed extremely valuable for comparison with mammalian DNA," remarked Ross Hardison, Professor of Biochemistry and Molecular Biology at Pennsylvania State University, "but there is still a lot of important stuff that doesn't match between humans and fish. I doubt Sydney Brenner would disagree." For instance, while the regulatory elements of some genes such as the Hox genes are conserved between humans and fish, Hardison says, "the exception is greater than the rule."

That said, "the Fugu genome may help to reveal information about the substantial areas of non-overlap between the Celera human genome and the version from the public consortium," he adds, "as well as homologs that don't exist in either data set." Brenner jokingly referred to the Fugu genome as a Reader's Digest version of its human counterpart. Hardison chuckled at the analogy. "There are some people who refuse to read Reader's Digest. It is a condensed version, after all," he said. "You can learn a lot from reading Reader's Digest - just not everything."

Completion and release of the genome is only the first step, the organizers say. Analysis begins now, and they hope to publish some of it by the end of the year. "An early answer is that the genome is hitting all of the human genes available to us," said Hawkins at a press conference. "We can see conserved elements jumping out at us that are not characterized as yet." The developers tested homologies against 1 million clones from four different human tissues to validate that they are actually expressed genes.