From duplication to fusion: Expanding Dayhoff's model of protein evolution.

Dayhoff's hypothesis suggests that complex proteins emerged from simpler peptides or domains, which duplicated and fused to create more complex proteins and novel functions. These processes expanded and diversified the protein repertoire within organisms. Extensive studies and reviews over the past two decades have highlighted the impact of gene duplication on protein evolution. However, the role of fusion in this evolutionary narrative remains less understood. This perspective seeks to address this gap by emphasizing the role of fusion in evolution. Fusion is critical in determining the evolutionary fate of duplicated protomers, either preserving their ancestral function or evolving entirely new functions. It complements mutations, insertions, and deletions as evolutionary steps to enhance protein evolvability by expanding the capacity of the protein to explore new structural and functional space.