In experimental tests of enzyme evolution, where a gene encoding an enzyme is subjected to multiple cycles of random mutagenesis and selection for altered substrate specificity, the resulting enzyme had multiple amino acid changes associated with altered substrate specificity. Where in the enzyme were these amino acid changes located?
A) only in the active site
B) only in the active site or near the active site
C) in or near the active site and at surface sites away from the active site
D) only at surface sites away from the active site
E) only in the hydrophobic interior of the folded protein
