Retracing Evolution With First Atomic Structure Of An Ancient Protein

Can you show any evidence of evolution by looking at the atomic structure of a protein? Scientists say yes. They have determined for the first time the atomic structure of an ancient protein. This reveals in detail how genes evolved their functions.

Recreating ancient progenitors of protein
The workhorses of the cell are proteins. But a detailed study showing how proteins have evolved has not been possible and has eluded evolutionary biologists. This was due because ancient proteins have not been available for direct study. So scientists used state-of-the-art computational and molecular techniques to re-create the ancient progenitors of an important human protein.

Looking at the Atoms
The challenge: can you use only the atoms of ancient proteins to trace changes in the atomic architecture? Two different groups of scientists worked together to trace how changes in the protein's atomic architecture over millions of years caused it to evolve a crucial new function -- uniquely responding to the hormone that regulates stress.

The ultimate level of detail
This is the ultimate level of detail and you can see exactly how evolution tinkered with the ancient structure to produce a new function that is crucial to our own bodies today.
The researchers focused on the glucocorticoid receptor (GR), a protein in humans and other vertebrates that allows cells to respond to the hormone cortisol, which regulates the body's stress response. The scientists' goal was to understand the process of evolution behind the GR's ability to specifically interact with cortisol.

How it was done
Scientists used computational techniques and a large database of modern receptor sequences to determine the ancient GR's gene sequence from a time just before and just after its specific relationship with cortisol evolved. The ancient genes existed more than 400 million years ago -- were then synthesized, expressed, and their structures determined using X-ray crystallography, a state-of-the art technique that allows scientists to see the atomic architecture of a molecule.

Results
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.