Scientists Retrace Evolution With First Atomic Structure Of An Ancient Protein

The structures allowed the scientists to identify exactly how the new function evolved. They found that just seven historical mutations, when introduced into the ancestral receptor gene in the lab, recapitulated the evolution of GR's present-day response to cortisol. They were even able to deduce the order in which these changes occurred, because some mutations caused the protein to lose its function entirely if other "permissive" changes, which otherwise had a negligible effect on the protein, were not in place first.

"These permissive mutations are chance events. If they hadn't happened first, then the path to the new function could have become an evolutionary road not taken," Thornton said. "Imagine if evolution could be rewound and set in motion again: a very different set of genes, functions and processes might be the outcome."The atomic structure revealed exactly how these mutations allowed the new function to evolve. The most radical one remodeled a whole section of the protein, bringing a group of atoms close to the hormone. A second mutation in this repositioned region then created a tight new interaction with cortisol. Other earlier mutations buttressed particular parts of the protein so they could tolerate this eventual remodeling.

"We were able to walk through the evolutionary process from the distant past to the present day," said Ortlund, who is now at Emory University in Atlanta. "Until now, we've always had to look at modern proteins and just guess how they evolved."

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