A University of Oregon research team has found that evolution can never go backwards, because the paths to the genes once present in our ancestors are forever blocked.

The team used computational reconstruction of ancestral gene sequences, DNA synthesis, protein engineering and X-ray crystallography to resurrect and manipulate the gene for a key hormone receptor as it existed in our earliest vertebrate ancestors more than 400 million years ago.

The discovery of evolutionary bridge burning implies that today's versions of life on Earth may be neither ideal nor inevitable, said Joe Thornton, a professor in the UO's Center for Ecology and Evolutionary Biology and the Howard Hughes Medical Institute.

"Evolutionary biologists have long been fascinated by whether evolution can go backwards," Thornton said, "but the issue has remained unresolved because we seldom know exactly what features our ancestors had, or the mechanisms by which they evolved into their modern forms.

We solved those problems by studying the problem at the molecular level, where we can resurrect ancestral proteins as they existed long ago and use molecular manipulations to dissect the evolutionary process in both forward and reverse directions."

Thornton's team, which included UO research scientist Jamie Bridgham and collaborator Eric A. Ortlund, a biochemist at Atlanta's Emory University, focused on the evolution of a protein called the glucocorticoid receptor (GR), which binds the hormone cortisol and regulates the stress response, immunity, metabolism and behavior in humans and other vertebrates.

"This fascinating study highlights the value of studying evolutionary processes," said Irene Eckstrand, who oversees evolution grants at the National Institutes of Health's National Institute of General Medical Sciences. "By showing how molecular structures are finely tuned by evolution, Dr. Thornton's research will have a broad impact on basic and applied sciences, including the design of drugs that target specific proteins."

"Fish fossil. Researchers resurrected and manipulate the gene for a key hormone receptor as it existed in our earliest vertebrate ancestors more than 400 million years ago. Over a rapid period of time, five random mutations made subtle modifications in the protein's structure that were utterly incompatible with the receptor's primordial form. (Credit: iStockphoto)"

Source: University of Oregon