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A critical consideration in the process of de novo protein architecture design and protein evolution is the folding pathway and behavior a protein undertakes in transitioning to its functional tertiary structure. Of particular interest is a cryptic element within protein primary structure that enables an efficient folding pathway, and is postulated to be a heritable element in the evolution of protein architecture, the "folding nucleus" (FN). However, almost nothing is known regarding how the FN changes as simpler peptide motifs join to form more complex polypeptides. To this effect, the structure and folding properties of foldable intermediates along the evolutionary trajectory of the β-trefoil protein type were tested. This study specifically used and compared data from Symfoil-4T (an engineered β-trefoil protein) to several mutants to show that the FN is acquired during gene fusion events, incorporating novel turn structure generated by gene fusion. Furthermore, the FN of β-trefoils are adjusted by circular permutation in response to destabilizing functional mutations to allow the survival of FN (which is made possible by the intrinsic C3 cyclic symmetry of β-trefoil architecture) identifying a selective advantage that helps explain extant cyclic structural symmetry in the proteome.