Yet to turn one protein with a distinctive folded structure into another with a completely novel structure and function requires specified changes at many, many sites—far more than Axe altered in his experiments.10 The number of changes necessary to produce a new protein fold typically exceeds the number of changes that will result in functional loss. Given this, the probability of the evolutionary process successfully traversing a functional landscape from one functional peak to another—all the while escaping functional loss each step along the way—is extremely small, with the probability
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