Chickens aren’t especially delicate or demanding. Ask anyone who keeps them: Chickens eat almost anything.
Terns, on the other hand, are quite selective: Winging their way over the wide sea, they eat only fish.
So you might think that chickens would have cast-iron stomachs capable of ingesting a variety of dubious ingredients without harm—while more-discriminating terns would be far more sensitive to contaminants in their food.
Yet for one dangerous and prevalent environmental pollutant, dioxin, the exact opposite is true. Chickens that eat large amounts of dioxin-contaminated food sicken and die. But terns regularly consume substantial amounts of dioxin-tainted fish in their diet with far fewer ill effects.
The life-or-death difference between these two bird species comes down to three tiny amino acids in one 858-amino-acid-long protein that both species possess, scientists reported in the May 2006 issue of the Proceedings of the National Academy of Sciences.
The protein contains the binding site for dioxin, and a difference of just two of these three amino acids apparently changes the binding site’s shape in terns, so that dioxin can’t fit it well. In chickens, dioxin fits the protein’s shape like a key in a lock—triggering the toxin’s harmful effects.
The finding raises the possibility of developing a test that wildlife resource managers could use to predict the susceptibility of wild, scarce, or protected species to environmental contaminants, said Sibel Karchner, a biologist at Woods Hole Oceanographic Institution (WHOI) and lead author of the study.
Dioxins are byproducts of high-temperature waste incineration and of industrial processes to manufacture pesticides and plastics. They also are created naturally by volcanism and forest fires. Ubiquitous and toxic, they affect virtually all vertebrates and have been linked to cancer and reproductive abnormalities in humans. Dioxin, as a trace contaminant of the defoliant Agent Orange, was linked to health effects in Vietnam veterans. Dioxin also was used in the 2004 poisoning of Ukrainian presidential candidate Victor Yushchenko.
Because chickens are so sensitive to dioxin, they are used as a model system to study mechanisms of dioxin’s effects. Moreover, having the protein, called the aryl hydrocarbon receptor, or AHR, is the sole reason for ill effects. Laboratory mice genetically engineered to lack AHRs are not affected by dioxin, while mice possessing AHR are poisoned.
Like all proteins, AHR is made of amino acid “building blocks” that are linked together. The particular sequence of amino acids determines how the protein folds into a three-dimensional shape. Within that folded shape, there is one region where dioxin fits and binds to the protein. When dioxin binds to the site, it triggers a process that alters the function and activity of other genes in the animals’ cells, causing harmful effects.
Small difference makes a big difference
Using molecular cloning techniques, Karchner and colleagues—Diana Franks and Mark Hahn of WHOI and Sean Kennedy from Environment Canada, National Wildlife Research Centre—determined the entire sequence of amino acids in the AHR proteins of chickens and terns.
“Two amino acids out of these three account for the entire difference in binding affinity for dioxin, and therefore have a major impact on the difference in sensitivity between the chicken and tern,” Karchner said. The chicken AHR has a seven-times-greater affinity, or binding strength, for dioxin than does tern protein, the researchers found.
The research confirms that the amino acid sequence in the binding region of the AHR protein may not have changed much from species to species over evolutionary history.
“We looked at only two birds: the domestic chicken (Gallus gallus) and the common tern (Sterna hirundo),” Karchner said, “but you might be able to predict sensitivity of other wild animals by looking at a short section of a gene or protein sequence rather than cloning the whole gene.”
Kennedy is continuing to sample many species of wild birds to compare their AHRs, in collaboration with Hahn and Karchner. Hahn and others are conducting similar research on some marine mammal species.
The study was supported by the Woods Hole Sea Grant program.