Short Peptide Amyloids Are a Potential Sequence Pool for the Emergence of Proteins

Under prebiotic conditions, peptides are capable of self-replication through a structure-based template-assisted mechanism when they form amyloids. Furthermore, peptide amyloids can spontaneously form inside fatty acid vesicles creating membrane enclosed complex structures of variable morphologies. This is possible because fatty acid vesicle membranes act as filters allowing passage of activated amino acids while some amino acids derived from the activated species become non-permeable and trapped in the vesicles. Similarly, nascent peptides derived from the condensation of the activated amino acids are also trapped in the vesicles. It is hypothesized that such preselected peptide amyloids become a sequence pool for the emergence of proteins in life and that after billions of years of cellular evolution, the sequences in the current proteome have diverged significantly from these original seed peptides. If this hypothesis is correct, it could be possible to detect the traces of these seed sequences in current proteomes. Here, we show for all possible 3, 6, 7, 8 or 9 residue sequence motifs that those motifs that are most amyloidogenic/aggregation prone are over-represented in extant proteomes compared to a sequence-randomized proteome. Furthermore, we find that there is a greater proportion of amyloidogenic sequence motifs in archaea proteomes than in the larger primate proteomes. This suggests that the evolution towards larger proteomes leads to smaller proportion of amyloidogenic sequences.