The inch-long fish in the laboratory vial wouldn’t catch any angler’s eye, not even as bait. A second specimen, although double in size, is equally unremarkable.
“If you plunked these two fish down in front of most people, they wouldn’t recognize them as the same species,” says David Kingsley, an associate investigator of the Howard Hughes Medical Institute and associate professor of developmental biology at Stanford.
But the fact that the two fish are far-flung cousins—one was trapped near Canada’s Queen Charlotte Islands, the other was taken from Scottish seas—makes Kingsley one happy researcher. The cold-water aquariums in his lab hold specimens from more than 30 locations around the world, and he is cross-breeding thousands of the unassuming little fish with the great big name: three-spine stickleback.
Scientists know that populations of sticklebacks were isolated from one another some 10,000 years ago, when melting glaciers dispersed them into tens of thousands of different lakes and streams. Generations of biologists have identified the dramatic differences that distinguish today’s sticklebacks, including body size, color, skeletal armor, fins and behavior. Now Kingsley is using the tools of molecular genetics and genomics in an effort to find the bases of those differences—in essence, identifying the genes that control the evolution of new traits in vertebrates.
If Kingsley dotes on sticklebacks, associate professor of developmental biology William Talbot, PhD ’93, is just as jazzed about zebra fish. In his tropical-temperature lab, Talbot is raising more than 15,000 blue, silver, yellow and variously striped zebras. After a gene or gene family is tentatively identified—in zebra fish or, sometimes, other vertebrates—Talbot tests its function by disabling it in zebra fish. Because zebra fish reproduce quickly and copiously, the genes’ roles soon become apparent.
Kingsley and Talbot, along with Richard Myers, chair of genetics and director of the Human Genome Center, have made such a splash with their research that they recently landed a five-year, $16 million Center of Excellence in Genomic Science grant from the National Human Genome Research Institute.
With their respective knowledge of sticklebacks, zebra fish and genomics, “we each bring something totally different to the table,” Myers says. “Some questions are better asked in one species,” adds Talbot. “If we need to knock out 100 genes, we would do that in the zebra fish, at least first. But a key part of the grant is understanding the natural variation that leads to differences, which is something we can’t address anywhere but [in the] stickleback.”
“These guys are trying to answer some fundamental questions about how species occur,” Myers says. “When we started the genome project, everybody knew, even strict human geneticists, that we were going to learn far more by studying organisms that we could manipulate and do experiments with.”
