Puffer Fish Genomes Swim into View

In under a year, less time than it takes to train a Japanese chef to safely prepare the potentially deadly seafood, an international research team has almost fully deciphered the unusually compact genetic code of the puffer fish Fugu rubripes. The effort of that team, and of a French-American collaboration that has unraveled the genome of another puffer fish, won’t make eating the delicacy any less risky, but it could help scientists identify human genes and the DNA sequences that govern their activity.

Fugu rubripes. DOE

“This is the next major step in the human genome project,” says Trevor Hawkins, director of the Department of Energy’s Joint Genome Institute in Walnut Creek, Calif., who helped unveil the F. rubripes genome at a meeting in San Diego last week.

In the culinary world, puffer fish are famous for producing a dangerous toxin that can make eating the fish someone’s last meal. As for biologists, they prize the fish for having the smallest known genome among vertebrates.

The puffer fish genome is relatively tiny because its genes are compact and it has little DNA between its genes. Overall, the fish’s genome is about one-eighth the size of the human one.

“You can think of it as the Reader’s Digest version of The Book of Man,” says Sydney Brenner of the Salk Institute for Biological Studies in La Jolla, Calif., who more than a decade ago argued for deciphering, or sequencing, a puffer fish’s genome. “I think it will be used extensively to sort out the human genome.”

Only about 3 percent of the human genome actually encodes proteins. The rest of the DNA consists of sequences that regulate gene activity and ones that serve no apparent purpose. Sifting through the latter, so-called junk, DNA for the genes and regulatory elements has been a formidable challenge.

By comparing the human and fish genomes, says Hawkins, scientists can find DNA sequences that evolution has preserved in starkly different animals, ones whose lineages diverged around 400 million years ago. Shared sequences are presumably genes or regulatory elements important, if not essential, for vertebrate life, he explains.

Comparing the two puffer fish genomes should also provide insight into the regulation of genes in vertebrates, says Eric Lander of the Whitehead Institute in Cambridge, Mass. He and his colleagues, along with investigators from Genoscope, France’s national DNA-sequencing center in Paris, are putting the finishing touches on the genome of the freshwater puffer fish Tetraodon nigroviridis.

The overall tally of genes in either fish may end up around 30,000, similar to the lowest estimates for the human genome. “The preliminary analysis suggests that the Fugu and human genome share an almost identical gene complement,” notes Hawkins.

That finding, combined with the obvious differences between a fish and a person, will probably reinforce a growing consensus among biologists that it’s not simply the number of genes that determines the complexity of an organism.

An excited Brenner already has plans to mine his long-sought fish genome for clues as to why the vertebrate brain is so different from an invertebrates’. “It’s been a real pleasure to realize Sydney’s dream,” says Hawkins.

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