By studying the effects of mutations on the ancient protein's physical architecture, Harms and Thornton also showed why permissive mutations are so rare. To exert a permissive effect, a mutation had to stabilize a specific portion of the protein the same part destabilized by the function-switching mutations without stabilizing other regions or otherwise disrupting the structure. Very few mutations, they showed, can satisfy all these narrow constraints.
"These results show that contingencythe influence of chance events on the way evolution unfoldsis built into the atomic structure of molecules," said Irene Eckstrand, Ph.D., of the National Institutes of Health's National Institute of General Medical Sciences, which provided substantial funding for the research. "If the results hold true for other systems, this will be a highly significant contribution to our understanding of exactly how proteins can evolve new functionsa process that accounts for the diversity of life and the origins of genetic variation."
While most prior discussions of historical contingency in evolution have focused on external events such as asteroid impacts, mass extinctions, climate change, Thornton and Harms showed that the intrinsic complexity of proteins as physical objects also makes evolution depend profoundly on low-probability chance events.
"It's very exciting to have been able to directly study alternative ancient histories," Thornton said. "If evolutionary history could be relaunched from ancestral starting points, we would almost certainly end up with a radically different biology from the one we have now. Unpredictable genetic events are constantly opening paths to some evolutionary outcomes and closing the paths to others, all within the biochemica
|Contact: Kevin Jiang|
University of Chicago Medical Center