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Our
Evolving Bodies UO biologist Joe Thornton has received the U.S. government's highest honor for early career scientists. He has long been interested in understanding the effects of pollutants on the human body, but some of his recent research also answers one of the most common arguments against evolution, he says. Thornton, associate professor of biology at the UO's Center for Ecology and Evolutionary Biology, studies how the receptors for steroid hormones, such as estrogen and testosterone, evolved their specific functions. He received a five-year, $911,000 Faculty Early Career Development Program grant from the National Science Foundation for this research, and the NSF nominated some of the people who won these grants to receive the 2006 Presidential Early Career Award for Scientists and Engineers (PECASE).
After a long selection process, which picked 56 winners nationwide, and being cleared by the FBI to meet the president, Thornton received the award at the White House in November. White House Science Advisor Dr. John Marburger presided over the ceremony, and each recipient got a handshake and a few words from the president, Thornton said. Scientific research is actually Thornton's second career. After receiving a B.A. in English from Yale University in 1987, he spent eight years working for Greenpeace's toxics campaign, helping communities stop major sources of chemical pollution. He developed expertise in the effects of chemicals on health and testified before Congress on the issue. "All of this made me very interested in biology, and it also made me see how powerful science can be in contributing to our understanding of nature and our relationship with it," Thornton said. When Thornton went back to school for a doctorate in biology at Columbia University, his dissertation was about steroid hormone receptors. These molecules in the cells of humans and other animals trigger the body's responses to hormones, which are chemicals produced by glands like the ovaries or testes. These chemicals travel throughout the body in the blood and cause radical changes in behavior, development and health. They are particularly vulnerable to pesticides and industrial chemicals, which can harm the reproductive system and cause cancer by mimicking or blocking the actions of estrogens, androgens and other steroid hormones, Thornton said. Thornton joined the UO faculty in 2002. Some of his highest-profile work involves "resurrecting" ancestral genes so that they can be studied in detail in the laboratory. One recent project explains the evolution of two steroid hormone receptors — one for the stress hormone cortisol and the other for aldosterone, which regulates kidney and colon function in response to changing salt conditions. Thornton wanted to know how these two receptors came to recognize these specific hormones. He and UO postdoctoral scientist Jamie Bridgham began by analyzing the gene sequences of a huge database of hormone receptors, using a bank of computers in his laboratory. They found that the two receptors originated when a single ancient receptor gene was copied in the genome some 450 million years ago — in the earliest days of vertebrate evolution. They used statistical methods to reconstruct the gene sequence of that ancient receptor, synthesized the gene as it existed in the ancient past and then used laboratory tests to determine its functions. They found that the ancestral gene worked beautifully and was sensitive to both aldosterone and cortisol. This result was surprising, Thornton said, because aldosterone itself didn't evolve for at least another 50 million years, around the time vertebrates came out of the water and began to colonize the land. But it explained how a new hormone-receptor pair evolved: When aldosterone came on the scene, the ancient receptor had been duplicated, and the new hormone recruited the receptor into a new functional relationship. This research was published in the journal Science in April 2006. An accompanying commentary by Christoph Adami of the Keck Graduate Institute of Applied Sciences in Claremont, Calif., described the importance of the finding. Even Charles Darwin saw specialized lock-and-key relationships, such as hormones and their receptors, as a point where his theory was potentially vulnerable, Adami wrote. Intelligent design advocates hold that such relationships demonstrate irreducible complexity and could not have evolved. "Although these authors have not directly addressed this controversy in the discussion of their work — because the work itself is intrinsically interesting to biologists — such studies solidly refute all parts of the intelligent design argument. Those 'alternate' ideas, unlike the hypotheses investigated in these papers, remain thoroughly untested. Consequently, whatever debate remains must be characterized as purely political," Adami concluded. Biochemist Michael Behe, a senior fellow with the pro-intelligent design Discovery Institute's Center for Science and Culture who coined the term "irreducible complexity," discussed the Science articles on his blog. He argued that what he considers irreducibly complex systems consist of multiple protein factors, not a single protein as in Thornton's study, and that the changes Thornton observed in the protein were similar to the sort of mutation and selection involved in bacteria becoming resistant to antibiotics, which intelligent design proponents accept. Thornton said political pressure in favor of intelligent design has not changed the scientific community's acceptance of evolution. He said that while his work supports evolutionary theory, and while he notes those implications of the work, that's not the primary reason he did the work. "It's evolution that's the explanation for why our bodies are the way they are, and I want to understand why our bodies work the way they do," Thornton said. Thornton went on to study why the ancient receptor was sensitive to both aldosterone and cortisol when aldosterone hadn't yet evolved. Collaborating with University of North Carolina scientists, Thornton's group grew the ancient protein in a flask and put it in a special salt solution so that it would form regular crystals. They used the Advanced Photon Source, a stadium-sized particle accelerator at Argonne National Laboratory in Illinois, to shine some of the most powerful X-rays in the world through the crystal, generating a precise map of the more than 2,000 atoms in the ancient receptor. This was the first time the atomic architecture of an ancient protein had ever been determined. They saw that the receptor binds aldosterone in precisely the same way that it binds the more ancient cortisol, with ample room to accommodate the subtle differences in shape that are unique to aldosterone. The receptor, Thornton said, was just a little bit sloppy, and this became the raw material from which evolution would later create a new hormone-receptor partnership. Thornton's group — which includes UO students and postdoctoral researchers — next determined how the cortisol receptor became specific for that hormone by reconstructing, experimentally characterizing and determining the structures of a series of ancient receptors from between 450 and 410 million years ago. They identified seven specific mutations that changed the receptor's non-specific function into a cortisol-specific receptor like the modern one. The structures showed that that two of the seven mutations radically changed the receptor's structure so that it strongly preferred cortisol to aldosterone, while three others completed a subtler remodeling that excluded aldosterone completely. The last two mutations did not affect the receptor individually, but they buttressed the parts of the structure that the three fine-tuning mutations changed, making the receptor able to tolerate the other changes. Thornton pointed out that these results, reported in Science in September 2007, point to the importance of chance events in evolution: Mutations that are initially unimportant may hang around for some time, creating opportunities for future mutations that may give rise to major innovations. "If those little changes had never occurred, we might have ended up with a very different biology from the one we have today," Thornton said.
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