Amino acid sequences shuffled

The observation of split genes led to the hypothesis that perhaps new proteins could be made by shuffling the DNA fragments of genes that code for parts of old proteins—much as cards can be picked from several piles to give a new arrangement. To support the hypothesis, advocates point to similarities in the amino acid sequences and shapes of discrete portions (called domains) of different proteins. 

Shuffle test. An enzyme that catalyzes disulfide-sulfhydryl exchange reactions, called protein disulfide isomerase (PDl), has been isolated. PDI rapidly converts inactive scrambled ribonuclease into enzymatically active ribonuclease. In contrast, insulin is rapidly inactivated by PDI. What does this important observation imply about the relation between the amino acid sequence of insulin and its three-dimensional structure ... 

The similarities in sequence in Figure 7 5 appear striking, yet there remains the possibility that a grouping of sequence identities has occurred by chance alone. How can we estimate the probability that a specific series of identities is a chance occurrence To make such an estimate, the amino acid sequence in one of the proteins is "shuffled"—that is, randomly rearranged—and the alignment procedure is repeated (Figure 7.7). This process is repeated to build up a distribution showing, for each possible score, the number of shuffled sequences that received that score. 

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