Fernndez and Lynch focused on design flaws called "dehydrons," sites where the protein structure is vulnerable to chemical reactions with water. Proteins with more dehydrons are more "unwrapped" - unstable in an aqueous environment, and therefore prone to bind with another protein to protect their vulnerable regions.
A computational analysis of 106 orthologous proteins confirmed their hypothesis that proteins from species with smaller populations were more vulnerable in water. The result suggests that structural errors accumulate in large organisms such as humans due to random genetic drift.
"We hate to hear that our structures are actually lousier," Fernndez said. "But that has a good side to it. Because they are lousier, they are more likely to participate in complexes, and we have a much better chance of achieving more sophisticated function through teamwork. Instead of being a loner, the protein is a team player."
On their own, these unstable proteins might be expected to perform their cellular duties more poorly, possibly causing harm to the organism. But unstable proteins are also "stickier," more likely to form associations with other proteins that could introduce more flexibility and complexity into the cell. If these complexes create a survival advantage for the organism, forces of natural selection should take over and spread the new protein complex through the population.
"It's not an argument against selection, it's an argument for non-adaptive mechanisms opening up new evolutionary pathways that wouldn't have been there before," Lynch said. "It's those first little nicks getting into the protein armor that essentially open up a new selective environment."
To confirm that the
|Contact: Robert Mitchum|
University of Chicago Medical Center