Zebra fish genome sequenced
They may not look like it, but zebra fish are genetically similar to people. (Genome Research Ltd. / December 31, 1969)
Scientists have moved one step closer to understanding how genes drive human biology and disease — and they've done it by mapping the DNA of a tiny, decidedly non-human creature known as the zebra fish.
In a study published Wednesday by the journal Nature, scientists at the Wellcome Trust Sanger Institute in Hinxton, England, announced that they had greatly improved their assembly of the zebra fish genome, identifying the precise order of nearly 90% of the 1.4 billion base pairs in the fish's DNA.
The feat makes the zebra fish one of only three vertebrates with such a high-quality genome assembled. The other two are people and mice.
"This is a mark of the genome's completion," said study senior author Derek Stemple, head of mouse and zebra fish geneticsat the Wellcome Trust Sanger Institute.
Since the 1980s, scientists have depended on studies in zebra fish as they've worked to decode the mysteries of human genetics, he said.
The fish, which cost about $1 in pet stores, make great research subjects for a number of reasons.
They're cheap, and they reproduce readily and quickly. Within a day, the embryos take on a fish-like form and begin developing organs. Zebra fish also remain see-through during much of their development, which lets researchers observe what's going on in their bodies without having to image or dissect them.
And despite having those attributes — not to mention gills, scales and bodies just a couple of inches long — zebra fish are genetically very similar to people.
If a researcher wants to study a gene's role in a human disease, he can quickly and inexpensively breed zebra fish with problems in the corresponding gene. Then, as the mutant fish grow, he can study how changes in the gene affect their biology and cause illness.
"We want to figure out what the genes in fish do, and use that to figure out what matching genes in humans do," said geneticist Shawn Burgess, a senior investigator at the National Human Genome Research Institute in Bethesda, Md., who uses zebra fish to study tissue regeneration.
It wouldn't be ethical to make human mutants, and in many cases it's too expensive and time-consuming to undertake the work in mice.
But interpreting findings in zebra fish depends on having an accurate record of where the zebra fish genes are. Technical issues, such as trying to resolve DNA differences among multiple individuals, had prevented researchers from getting a clear picture of the genome in the past.
"Now, you can find the equivalent gene in a human and have confidence that the match is correct," Stemple said.
The new genome data revealed that 70% of human genes have at least one closely related gene in the fish.
Burgess, who was not involved in assembling the new genome, said its precision would make his work much easier.
"It's the difference between driving a Yugo and driving a BMW," he said.
Experts also hailed a complementary collaboration in which Stemple and colleagues altered zebra fish sperm in a way that enabled the scientists to sequence offspring DNA and identify "potentially disruptive" mutations in about 40% of the zebra fish's 26,000 protein-coding genes. That report was also published by Nature on Wednesday.
Within a year, Stemple said, the team expects to have identified mutations in all of the protein coding genes.
Scientists can now use the sperm to make zebra fish families and test the mutations' effects with unheard-of efficiency.
"Now, they have a freezer full of mutants. That's a huge resource for the community," Burgess said. "Theoretically, they can test the function of every gene in the genome in five years."
Stanford neuroscientist William Talbot said the "catalog of mutations" would contain useful specimens for many researchers working with zebra fish.
"There's a good chance there's already a fish with a mutation in any given gene that you can just order and be ready to study right away," he said
Stemple said scientists would like to use zebra fish studies to identify drugs to combat diseases that today can't be treated.
His team will continue to fine-tune the sequences, he said. They hope to publish another improved version of the zebra fish genome within a year.