An AI-generated illustration depicts the convergent evolution of intrinsically disordered regions in vertebrate galectins, showing how repeated molecular segments can give rise to similar functions across species.

Different Ingredients, Similar Results

Proteins are often associated with precise, folded structures. But many also contain intrinsically disordered regions—flexible stretches that do not adopt a single stable shape.

Huang’s team investigated these regions in vertebrate galectins, including human galectin-3. Their interactions help proteins gather into concentrated assemblies through a process known as phase separation, enabling them to cluster sugar-bearing molecules. Galectins participate in biological processes, including immune responses and cell communication.

Earlier studies using short peptides had emphasized the importance of particular aromatic amino acids, suggesting that the identity of these molecular “sticky points” strongly influences assembly.

Yet comparisons across species revealed different ingredients capable of supporting a similar function. Human galectin-3 contains repeated segments rich in tyrosine, while the zebrafish galectin examined by the team predominantly uses tryptophan. Both can promote molecular clustering. That raised a question: How could proteins with different components arrive at a similar result?
 

Building Strength Through Repetition

The team’s experiments pointed to the number of repeated segments as a major factor. Increasing those repeats strengthened the protein’s capacity to assemble and drive clustering more substantially than changing the type of aromatic amino acid. The finding suggests that repetition can provide an effective evolutionary route to stronger function, without requiring the same molecular ingredients in every species.

Huang likened the process to the computer commands “Ctrl+C” and “Ctrl+V.” Starting with a short, useful sequence, successive duplications can expand the number of interacting segments, allowing their combined effects to build.

The researchers propose that different vertebrate lineages independently expanded these segments, converging on similar clustering functions. In this model, evolution builds on existing modules, with further changes adapting them to each species’ needs.

The conclusion is not that amino acid identity is irrelevant. Rather, the study identifies repeat number as a more influential factor in the galectins examined, challenging an explanation centered primarily on the choice of individual aromatic amino acids.

New Possibilities for Protein Engineering

The findings offer a potential design principle for protein engineering and synthetic biology: adjusting the number of functional modules could help researchers tune how proteins assemble.

Such an approach could inform the development of biomedical materials with specific phase-separation properties. It may also guide future investigations into molecular mechanisms associated with abnormal protein condensation.

Those applications remain possibilities for further research. The study’s immediate contribution is a clearer picture of how flexible protein regions can acquire function through repetition—a molecular version of building on what already works.

The research team, from left: doctoral student Yu-Hao Lin, Professor Jie-Rong Huang and master’s student Yu-Chen Chen.