such as "Introduction", "Conclusion"..etc
August 17, 2007 -- Scientists have determined for the first time the atomic structure of
an ancient protein, revealing in unprecedented detail how genes evolved
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.
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.
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."
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
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.
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."Source : University of Oregon
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