Evolution of Folded Domains from Short, Oligomerizing Peptides through Coacervation

In 1966, Margaret Dayhoff reasoned that duplication and fusion is a fundamental mechanism for generating protein complexity. Her insight inspired generations of scientists, several of whom would demonstrate this trajectory with short peptides that symmetrically assemble into a contemporary protein architecture. But how did these oligomerizing peptides, able to adopt complex conformations, emerge in the first place? In the present review, the evolution of an ancient and ubiquitous nucleic acid-binding element is traced from a simple, heterochiral peptide that coacervates with RNA to a folded-domain that binds with high affinity to the minor groove of double-stranded DNA.