Copyright 2003 The Oregonian
The Oregonian
September 24, 2003 Wednesday SUNRISE EDITION
SCIENCE; Pg. C11
RICHARD L. HILL - The Oregonian

UO SCIENTISTS REBUILD ANCIENT EXTINCT GENE

Reconstructing a 600-million-year-old gene may evoke images of dinosaur-creating scientists in fictional "Jurassic Park," but it's a real-life feat for an Oregon scientist.

Evolutionary biologist Joe Thornton of the University of Oregon not only determined the ancient gene's structure, but made the gene function in the lab. The gene is for a vital protein called a steroid hormone receptor.

The study demonstrated that the female hormone estrogen is the most ancient of the steroid hormones, emerging during the earliest days of animal evolution, when primitive sponges and jellyfish ruled the planet.

In addition, the research suggests that steroid hormone receptors -- which are in the cells of humans and other vertebrates -- may be widespread in invertebrates as well. The researchers speculate that their finding may mean that hormone-disrupting chemicals such as DDT and PCBs may pose a threat to more animals than has been thought.

Thornton and researcher Eleanor Need, both with the UO Center for Ecology and Evolutionary Biology, and biologist David P. Crews of the University of Texas at Austin reported their findings Friday in the journal Science.

The research, made possible by high-speed computers and advances in biochemical techniques, enables scientists to study long-extinct molecules that could provide insights into today's biological systems.

Only a handful of studies have resurrected extinct genes, but this is one of the oldest genes ever re-created. Researchers at the University of Florida reported in the current issue of the journal Nature that they resurrected an ancient bacterial gene that goes back more than 1 billion years.

"Our goal is to understand the revolutionary process by which modern-day animals, including humans, got our repertoire of hormones -- how they and their functions evolved," Thornton said.

In search of hormones' origins


The study focused on steroid hormones, compounds that include the well-known sex hormones estrogen and testosterone. Steroid hormones are critical to a variety of biological processes, regulating many aspects of reproduction, development, immunity, behavior and response to stress and changing environments. As a hormone circulates in the blood, it binds to a specific receptor, a protein that regulates a gene when its hormone partner is present.

"We wanted to understand the origin of steroid hormones and their receptors," Thornton said, "so we resurrected the very first receptor, and we've found that its partner was estrogen."

To conduct the study, the researchers isolated the gene for a steroid hormone receptor from a present-day mollusk, the sea slug Aplysia californica. "It's distantly related to the vertebrates in which these receptors have been previously identified," Thornton said. "So the fact that a mollusk has an estrogen receptor and vertebrates do as well, means that the common ancestor of mollusks and human beings also had one."

Applying sophisticated statistical techniques to a large number of present-day receptors, the researchers then were able to infer the DNA sequence of the ancestral gene. From that genetic blueprint, they used biotechnology techniques to re-create a copy of the gene. They then transferred the gene into living vertebrate cells and grew them in a lab dish to produce large quantities of the ancient steroid hormone receptor.

The receptor responded only to estrogens, indicating that other hormones evolved more recently.

"This is very fascinating work," said David Hillis, an evolutionary biologist at the University of Texas at Austin who was not involved in the research. "These kinds of studies allow us to look at the functional changes that have occurred through long periods of time."

Predicting evolution

Hillis said such research could provide information about what evolutionary changes occur in response to environmental changes. "Since we often have a good idea about what kind of environmental changes we are facing," he said, "it can give us the ability to predict what changes are likely to occur in response to those."

Forty years ago, Portland native Linus Pauling and Emile Zuckerkandl proposed in a paper that it should be possible to infer the sequences of ancient genes and proteins by comparing the sequences of their modern descendants.

"They even said it might one day be possible to synthesize the inferred ancestral sequences," Thornton said. "And it is, now. At the time they wrote this, it was entirely speculative -- but quite prophetic."

Thornton, an assistant professor who has been at the UO for a year, said the next step is to trace the changes the gene underwent that allowed it to evolve a bond with new hormones.

The author of a book on global chemical pollution, "Pandor's Poison," Thornton hopes the discovery of the steroid hormone receptor in the sea slug will lead to efforts to control endocrine-disrupting chemicals in the environment.

"We need to start addressing the potential effects of these chemicals on invertebrates," he said, "because these animals are so ecologically important." Richard L. Hill: 503-221-8238; richardhill@news.oregonian.com

GRAPHIC: Photo -- JOE THORNTON - Findings published in journal Science

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