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Sequenced. Decoding the DNA of 21 threespine stickleback fish (inset) showed the importance of regulatory changes in the evolutionary transition from a marine form, with bony plates (bottom), to a freshwater form (

(fish drawings) Felicity Jones/Stanford U.; (photo inset) Tim Howes/Stanford U.

How Evolution Copies Itself

A tiny fish is helping to answer a big question about evolution. The threespine stickleback (Gasterosteus aculeatus) has long been abundant in the sea. But after glaciers melted 10,000 years ago, many wound up in new freshwater lakes and streams. In these unfamiliar environments, the fish lost their bony plates and spines and developed novel behaviors and physiology. A new study reveals that many of these relatively rapid changes were due not to mutations in specific genes, as some biologists had long assumed, but rather to changes in the activity of these genes. The finding should help focus more attention on the role of gene regulation in evolution, not just of fish but of all organisms, including humans.

For decades, evolutionary biologists have been fascinated by the repeated evolution of freshwater traits in marine sticklebacks. In these fish, evolution has duplicated itself thousands of times as marine ancestors moved into fresh water in many parts of the Northern Hemisphere, including Alaska, California, Europe, and Japan. All of these fish have undergone similar changes in their kidneys, body shape, eye size, and number of bony plates on their bodies. David Kingsley, an evolutionary biologist at Stanford University in Palo Alto, California, took advantage of this parallel evolution to look at how the genome causes these changes.

He, Kerstin Lindblad-Toh of the Broad Institute in Cambridge, Massachusetts, and their colleagues first sequenced the DNA of a stickleback from a lake in Alaska to a high degree of accuracy. With this reference sequence as a guide, the researchers were able to, with less work, sequence the genomes of 10 additional pairs of sticklebacks from around the world. Each pair consisted of a marine individual and its nearby freshwater relative.

Typically, any gene should be most similar among fish from the same location. But if there was repeated evolution at a particular region of the genome, that region should be alike in all the freshwater fish, irrespective of how close they lived to each other. Kingsley's team scanned all the genomes for regions where repeated evolution had occurred, finding 147 of them and confirming that repeated evolution was rampant in these fish.

Next, the researchers counted how many of these regions contained a gene. Then they compared the sequences of that gene among the different fish. If the genes were the same in all the freshwater fish but different from a marine counterpart, the researchers assumed that the gene itself was responsible for the adaptation to fresh water. That happened in only 17% of the regions, Kingsley and his colleagues report online today in Nature. Meanwhile, about 41% of the regions contained no gene, indicating that changes responsible for the adaptation were regulating the activity of genes elsewhere in the genome. Another 43% contained a gene and regulatory DNA, but because only the regulatory DNA was the same among the freshwater fish, the researchers assumed that regulatory changes were at the heart of those adaptations as well.

Researchers have documented repeated evolution in other organisms, but the sticklebacks are unique because the freshwater transition has occurred so many times. "Sticklebacks have been a phenomenal system for understanding rapid evolution," says evolutionary biologist Erica Bree Rosenblum of the University of California, Berkeley, who wasn't involved in the study. "This paper shows that repeated evolution can occur by 'reusing' the same genetic mechanisms over and over again."

For now, Kingsley has a genome-wide accounting of the reused genetic changes involved in the transition to freshwater but doesn't know most of the traits those changes control. He and other researchers are now trying to track those down. "That will be the big next step," says Hopi Hoekstra, an evolutionary biologist at Harvard University, who was not involved in the study.