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Weizmann Insitute scientists show how proteins beat the evolutionary stakes

Evolution is something of a gamble: in order to stay a step ahead of a shifting environment, organisms must change or risk extinction. Yet the instrument of this change, mutation, carries a serious threat: mutations are hundreds of times more likely to be harmful to the organism than advantageous. Now, in a paper published online Nov. 28 in Nature Genetics, a team of scientists at the Weizmann Institute of Science has shown one way that evolving organisms may be hedging their bets.

Dr. Dan Tawfik, who headed the team from the Biological Chemistry Department, believes that proteins with so-called promiscuous or moonlighting activities can provide nature with ready-made starting points for the evolution of new functions. Proteins that have evolved to perform a given function often have the ability to take on other, often completely unrelated tasks as well. For example, one of the enzymes studied by the group, PON1, is known to remove cholesterol from artery walls, as well as to break up a certain chemicals used as pesticides.

Yet its main function is to act as a catalyst for the removal of a class of compounds called lactones that have no connection at all to the other two.

To investigate what kind of evolutionary advantage promiscuity offers, the team created a speeded-up version of evolution in the lab. Mutations were introduced into the genes coding for various proteins in a completely random manner. Evolutionary pressure was then simulated by selecting those mutants with higher levels of activity in one of the promiscuous traits.

After several rounds of mutation and selection, the scientists looked at their enzymes to see what had changed. As expected, they had managed to increase the activity they were selecting for by as much as a hundredfold and more. But how did increasing one skill affect the others?

Interestingly, the levels of the other promiscuous activities also underwent drastic changes. In most cases, the lev
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Contact: Yivsam Azgad
yivsam.azgad@weizmann.ac.il
American Committee for the Weizmann Institute of Science
21-Dec-2004


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