A competition of molecules: Natural Selection in its tiniest form

Prion Protein (PrP) is a normal protein found in healthy cells, though its exact role is not yet clear. However, when this protein changes shape into a misfolded form, it becomes infectious and is linked to deadly brain diseases like Creutzfeldt-Jakob disease. The misfolded protein can force normal PrP proteins to also misfold and stick together, forming long structures called fibrils. These misfolded proteins can have slightly different shapes, which are linked to variations in disease symptoms, known as prion strains.

In a study published in ACS Nano, Yuanzi Sun and colleagues used a microscope to watch prion fibrils grow on a slide with the necessary precursor PrP proteins and aqueous solution. They noticed differences between individual prion fibrils and grouped them based on these differences. When they changed the solution's composition, some fibril types grew and replicated better than others. Interestingly, the fibrils occasionally made errors during replication, creating slightly different structures—similar to mutations.

This ability of fibrils to replicate, mutate, and compete represents a kind of molecular evolution, like natural selection happening at the level of protein structures. This challenges previous ideas that fibrils always grow in the same way, regardless of conditions. It also highlights a form of evolution that doesn’t involve DNA, offering new insights into how biology works.

The senior author of the study Professor Jan Bieschke said: “I find it amazing that the same principles that govern the evolution of life also apply to these simple protein systems.”