Origin of life: β-sheet amyloid conformers as the primordial functional polymers on the early Earth and their role in the emergence of complex dynamic networks.

The origin of life has remained a conundrum. Among the origin-of-life hypotheses, the RNA world has gained wide popularity. It has, however, been difficult to explain the emergence of both stable and meaningful RNA under the presumably very harsh early Earth conditions, and it has been assumed that some other replicating system must have preceded the RNA world. The amyloid world hypothesis posits that the first functional polymers on the primitive Earth were structurally stable self-replicating β-sheet-based peptide amyloids. The amyloid hypothesis is examined in this perspective in light of new research results and highlights the role of dynamic interacting networks. The mechanisms of self-amplification and information transfer are discussed, as well as the catalytic, adaptive, and evolutionary properties of the cross-β-sheet ensembles. There is no contradiction between the amyloid and the RNA world hypotheses: In the harsh prebiotic environment, the β-sheet fibrillar networks provide a scaffold and initial protection for nucleobases and other prebiotic compounds, and the cooperative interactions of the β-sheet ensembles with nucleic acids, fatty acids, and natively folded proteins are in concert with the view of an early co-evolving amyloid-RNA-lipid-protein world.