Sydney Brenner, who pioneered the genetic analysis of C. elegans, looks with pride at the discoveries his former students and others have madeand are still making--with the little worm. He is happy that its entire genome has been sequenced. Personally, though, he has moved on to another organism: the pufferfish, or Fugu (Fugu rubripes), a rather ungainly, spotted fish that puffs up into a ball when it feels threatened.
Fugu is considered a great delicacy in Japan, where it is prized both for its tingling taste and its whiff of danger. Unless properly prepared (bred without certain bacteria or totally cleared of bacterial toxins), Fugu can rapidly paralyze and kill humans. In fact, hundreds of people have died of Fugu poisoning. But Brenner values Fugu for an entirely different reason: its exceptionally compact and gene-rich DNA.
"I call it the 'discount genome,'" says Brenner, who does much of his research at the Molecular Sciences Institute in Berkeley, California. "Fugu's genome is only 400 megabases, about one-eighth the size of the human genome, yet it has roughly the same number of genes as the human, as we have proved."
This gene density makes Fugu DNA much easier to work with than human DNA, Brenner explains. It is difficult to identify human genes in a sea of genomic DNA, even after the DNA has been fully sequenced, since protein-coding genes are usually made up of several pieces separated by "introns" (intervening sequences) and represent less than 5 percent of the total human genome. The vast bulk of the genome consists of stretches of uninterpretable DNA that include many repetitive sequences between genes, as well as in the introns that interrupt the genes and are later spliced out to form messenger RNA. In Fugu, however, there is very little repetitive DNA and the introns are much smaller, yet the coding sequences are the same size. As a result, genes make up 20 percent of Fugu's total DNA. "This means you don't have to sequence all that rubbish," Brenner says. "We can find genes in the fish genome which you can't find in the human, but once you find a gene in the fish, you can look for it in the human."
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This pufferfish, Fugu, can swell into a ball when it feels threatened. Its value for researchers, Brenner explains, is that "it has no junk DNA. In one-eighth the size of the human genome, it's got all of the genes."
Photo: B. Venkatesh