Mutant Fish Safely Store Toxins in Fat

thttp://www.wired.com/wiredscience/2011/02/fish-toxins-environment/

Some fish in New York’s Hudson River have become resistant to several of the waterway’s more toxic pollutants. Instead of getting sick from dioxins and related compounds including some polychlorinated biphenyls, Atlantic tomcod harmlessly store these poisons in fat, a new study finds.

But what’s good for this bottom-dwelling species could be bad for those feeding on it, says Isaac Wirgin of the New York University School of Medicine’s Institute of Environmental Medicine in Tuxedo. Each bite of tomcod that a predator takes, he explains, will move a potent dose of toxic chemicals up the food chain — eventually into species that could end up on home dinner tables.

From 1947 to 1976, two General Electric manufacturing plants along the Hudson River produced PCBs for a range of uses, including as insulating fluids in electrical transformers. Over the years, PCB and dioxin levels in the livers of the Hudson’s tomcod rose to become “among the highest known in nature,” Wirgin and his colleagues note online Feb. 17 in Science. Because these fish don’t detoxify PCBs, Wirgin explains, it was a surprise that they could accumulate such hefty contamination without becoming poisoned. His team now reports that the tomcod’s protection traces to a single mutation in one gene. The gene is responsible for producing a protein needed to unleash the pollutants’ toxicity.


All vertebrates contain molecules in their cells that will bind to dioxins and related compounds. Indeed, these proteins — aryl hydrocarbon receptors, or AHRs — are often referred to as dioxin receptors. Once these poisons diffuse into an exposed cell, each molecule can mate with a receptor and together they eventually pick up a third molecule. This trio can then dock with select segments of DNA in the cell’s nucleus to inappropriately turn on genes that can poison the host animal.

The tomcod actually has two types of AHRs, with AHR-2 offering the most effective binding to dioxin-like pollutants. But one naturally occurring AHR-2 variant, the result of a gene mutation, proves a very poor mate, Wirgin’s team has found. It takes five times more of the pollutants to get substantial binding than is needed with the conventional AHR-2.

In local rivers relatively free of dioxins and PCBs, 95 percent of tomcod possess AHR-2 only in the conventional form. But in the PCB-rich Hudson, Wirgin’s group finds, the only kind of AHR-2 protein in 99 percent of tomcod is the poorly binding variant.

The mutant receptor appears to have evolved long ago and to be widely dispersed. But in the Hudson, fish with the gene to make the mutant receptor have thrived, while those without it have died out, Wirgin notes.

Adaptation to resist poisons occurs throughout biology, observes molecular toxicologist John Stegeman of the Woods Hole Oceanographic Institution in Massachusetts. This process explains why some pesticides no longer kill their targets and why some microbes become immune to antibiotics.

Stegeman has been chronicling resistance to toxic PCBs and polycyclic aromatic hydrocarbons in another coastal species, a killifish. “But the mechanism in the killifish has not been uncovered, despite a long effort to determine it,” he says.

Knowing the genetic underpinnings for chemical resistance can help predict the likelihood of that resistance developing, he explains, and can point to “how one might exploit resistance — even understand why chemicals are toxic.” Genetic mechanisms for chemical resistance in wild species are known for some invertebrates, such as bugs. Stegeman says, to his knowledge, this tomcod finding is the first in a vertebrate.