Navigation Links
Scientists retrace evolution with first atomic structure of an ancient protein

EUGENE, Ore.(Aug. 16, 2007)Scientists have determined for the first time the atomic structure of an ancient protein, revealing in unprecedented detail how genes evolved their functions.

"Never before have we seen so clearly, so far back in time," said project leader Joe Thornton, an evolutionary biologist at the University of Oregon. "We were able to see the precise mechanisms by which evolution molded a tiny molecular machine at the atomic level, and to reconstruct the order of events by which history unfolded."

The work involving the protein is detailed in a paper appearing online Aug. 16 in Science Express, where the journal Science promotes selected research in advance of regular publication.

A detailed understanding of how proteins the workhorses of every cell have evolved has long eluded evolutionary biologists, in large part because ancient proteins have not been available for direct study. So Thornton and Jamie Bridgham, a postdoctoral scientist in his lab, used state-of-the-art computational and molecular techniques to re-create the ancient progenitors of an important human protein.

Thornton then collaborated with University of North Carolina biochemists Eric Ortlund and Matthew Redinbo, who used ultra-high energy X-rays from a stadium-sized Advanced Photon Source at Argonne National Laboratory near Chicago to chart the precise position of each of the 2,000 atoms in the ancient proteins. The groups then 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.

"This is the ultimate level of detail," Thornton said. "We were able to see exactly how evolution tinkered with the ancient structure to produce a new function that is crucial to our own bodies today. Nobody's ever done that before."

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. They 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 which 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. The project represents the first time the technique has been applied to 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."


Contact: Zack Barnett
University of Oregon

Related biology news :

1. Wisconsin scientists grow critical nerve cells
2. Scientists ID molecular switch in liver that triggers harmful effects of saturated and trans fats
3. UCSB scientists probe sea floor venting to gain understanding of early life on Earth
4. UAB scientists discover the origin of a mysterious physical force
5. Fox Chase Cancer Center scientists identify immune-system mutation
6. Scientists Replicate Hepatitis C Virus in Laboratory
7. Scientists detect probable genetic cause of some Parkinsons disease cases
8. Scientists find missing enzyme for tuberculosis iron scavenging pathway
9. Scientists seek answers on what activates deadly anthrax spores
10. Yale Scientists Find MicroRNA Regulates Ras Cancer Gene
11. Scientists collaborate to assess health of global environment
Post Your Comments:
(Date:6/9/2016)... 9, 2016 Paris Police ... video security solution to ensure the safety of people and ... during the major tournament Teleste, an international technology ... services, announced today that its video security solution will be ... back up public safety across the country. The system roll-out ...
(Date:6/2/2016)... The Weather Company , an IBM Business (NYSE: IBM ... which consumers will be able to interact with IBM Watson ... or text and receive relevant information about the product or ... long sought an advertising solution that can create a one-to-one ... valuable; and can scale across millions of interactions and touchpoints. ...
(Date:5/20/2016)... 20, 2016  VoiceIt is excited to announce ... By working together, VoiceIt and VoicePass ... and VoicePass take slightly different approaches to voice ... security and usability. ... new partnership. "This marketing and technology ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... ... June 24, 2016 , ... While the majority of commercial spectrophotometers and fluorometers ... the 6000i models are higher end machines that use the more unconventional z-dimension of ... beam from the bottom of the cuvette holder. , FireflySci has developed several ...
(Date:6/23/2016)... WI (PRWEB) , ... June 23, 2016 , ... ... supplements, is pleased to announce the launch of their brand, UP4™ Probiotics, into ... for over 35 years, is proud to add Target to its list of ...
(Date:6/23/2016)... 23, 2016 A person commits a crime, and ... to track the criminal down. An outbreak of ... Drug Administration (FDA) uses DNA evidence to track down the ... Sound far-fetched? It,s not. The FDA has increasingly used a ... of foodborne illnesses. Put as simply as possible, whole genome ...
(Date:6/23/2016)... 23, 2016  The Prostate Cancer Foundation (PCF) is pleased to ... faster cures for prostate cancer. Members of the Class of 2016 were selected ... Read More About the Class of 2016 PCF Young Investigators ... ... ...
Breaking Biology Technology: