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Decoding the Mystery Fish

Decoding the Mystery Fish

Scientists delve into the genome of the African coelacanth


Few marine animals capture biologists’ imaginations more than the mysterious, almost mythical coelacanth, a 5-foot-long fish that was thought to have gone extinct in the age of dinosaurs—until a live one was found in 1938.

This week an international team of 91 researchers, including four from Woods Hole Oceanographic Institution, reported in the journal Nature that it has decoded the coelacanth’s entire genome. Searching deep into genes and far back in time, the scientists are exploring the mechanisms by which fish emerged onto land some 400 million years ago, beginning the evolution that has led to air-breathing, four-legged land animals (tetrapods).

The researchers “annotated” the complete sequence of nearly three billion nucleotides (guanine, adenine, thymine, and cytosine) in the coelacanth’s DNA—that is, they identified short sections of the DNA that correspond to particular genes, which encode instructions to make proteins that organisms need to function.

The project was led by Chris Amemiya of the Benaroya Research Institute and the University of Washington and Jessica Alföldi and Kerstin Linblad-Toh at the Broad Institute in Boston, Mass. Among the 91 researchers who reported on the coelacanth genome were four WHOI biologists: John Stegeman, Jed Goldstone, Mark Hahn, and Sibel Karchner.

The number of scientists is not large for genome work, Stegeman said. “There are lots of gene families, and nobody specializes in all of them. You bring in people who can make sure the whole classification is done accurately, from their knowledge of specific gene families. Jed and I had experience annotating certain genes in the zebra fish and the sea urchin. I was involved in early discussions of the project, and when annotation began, and I immediately brought in Mark and Sibel, Jed, and a collaborator, David Nelson, from the University of Tennessee, who, along with Jed, is an expert on identifying the particular genes we work on.”

Fins into limbs

Coelacanths belong to a group of fish dating back more than 418 million years called lobe-finned fishes because of their fleshy, limb-like fins. Scientists thought that the coelacanth could be a living relative of the first fishes with fins that were better adapted to crawl onto land.

“The team looked for genes or gene families that were lost during that transition because they were no longer needed, or that were expanded because there was a need for more genetic diversity in a particular function,” said Hahn.

The study identified key genes that land animals have, but coelacanths do not, including genes related to smell and detecting airborne odors; some immune-system genes (suggesting that land animals might have needed new ways to cope with pathogens); and genes involved in excreting nitrogen (fish excrete ammonia into the water; land animals convert ammonia to urea before excretion).

The scientists also studied coelacanth genes related to limb formation and saw differences between coelacanths and tetrapods. The researchers concluded that the closest living marine relatives to tetrapods are not coelacanths, but another ancient fish group called lungfishes.

Detoxification genes

Stegeman and Hahn said that the work in their and Nelson’s laboratories was a minor part of the entire effort. The coelacanth genes they studied are, so far, not remarkably different from the same genes in other animals, including fishes and tetrapods.

“We did genes that are part of what we call the ‘chemical defensome,’ a suite of genes that defend against harmful chemicals,” Stegeman said.

Hahn and Karchner examined a family of genes that includes the “AHR” (“aryl hydrocarbon receptor”) genes, which make AH receptor proteins that bind to planar, ring-shaped chemicals, such as the toxic chemicals called dioxins. Stegeman and Goldstone examined “cytochrome P450” genes, also called CYP (pronounced “sip”) genes, a family of genes involved in detoxifying manyhydrocarbon contaminants.

In a simplified view, the two types of genes work together in a one-two-punch: AH receptor proteins attach to contaminants and act as a signal to tell the cell to make more CYP proteins made by the CYP genes. These proteins detoxify and rid the cell of the contaminants.

“This work is part of the bigger picture of trying to understand the evolutionary history of these genes,” Hahn said. “The idea is that at some point early in the evolution of vertebrates, there was a selective pressure for animals to evolve a contaminant-detoxification system that could be induced by the very contaminants they were exposed to.”

“The coelacanth genome is still being examined, and there are certain to be some surprises in the coming months,” Stegeman said. What the WHOI researchers would like to do next is use the coelacanth gene sequences they now have to make the AHR and CYP proteins those genes code for. Then they can study the function of the proteins. Learning about the different actions or effects of proteins from evolutionarily older species such as coelacanths may yield clues to how vertebrates evolved.

“When a biologist first hears about coelacanths, there’s an immediate fascination, almost always,” said Stegeman. “I know there was for me. Working on this was almost like a dream come true.”

Research on the coelacanth genome by WHOI scientists was supported in part through grants from the National Institute of Health (NIH), the National Institute of Environmental Health Sciences (NIEHS), and the National Human Genome Research Institute (NHGRI).