Sensitivity to Dioxin Varies with Protein Makeup
Reported in Oceanus, a publication of the Woods Hole Oceanographic Institution
(Beyond Pesticides, June 21, 2006) Scientists at the Woods Hole Oceanographic Institution (WHOI), Woods Hole, MA, studied two birds: the domestic chicken (Gallus gallus) and the common tern (Sterna hirundo), to determine the impact of the environmental pollutiant, dioxin, on the species. They found that chickens that eat large amounts of dioxin-contaminated food sicken and die, but the terns, who regularly consume substantial amounts of dioxin-tainted fish in their diets, had far fewer ill effects.
The difference between these two bird species were three tiny amino acids in one 858-amino-acid-long protein that both species possess. 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.
Dioxins are byproducts of high-temperature waste incineration and of industrial processes to manufacture pesticides and plastics and are ubiquitous in the environment. They affect virtually all vertebrates and have been linked to cancer and reproductive abnormalities in humans. Dioxin was a major component of the defoliant Agent Orange and 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.
Using molecular cloning techniques, WHOI biologist, Sibel Karchner, and colleagues—Diana Franks and Mark Hahn, 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. Their results are reported in the May 2006 issue of the Proceedings of the National Academy of Sciences.
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 Karchner.