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Abstract:
For the most part, contemporary proteins can be traced back to a basic set of a few thousand domain
prototypes, many of which were already established in the Last Universal Common Ancestor of life on
earth, around 3.5 billion years ago. The origin of these domain prototypes, however, remains poorly un-
derstood. We have proposed that they arose from an ancestral set of peptides, which acted as cofactors
of RNA-mediated catalysis and replication [ASL15]. Initially, these peptides were entirely dependent
on the RNA scaffold for their structure, but as their complexity increased, they became able to form
structures by excluding water through hydrophobic contacts, making them independent of the RNA
scaffold. Their ability to fold was thus an emergent property of peptide-RNA coevolution.
