The first peptides: the evolutionary transition between prebiotic amino acids and early proteins

TL;DR

This paper explores the characteristics of the first peptides on early Earth, identifying conserved motifs in modern proteins that may trace back to prebiotic origins and early catalytic functions.

Contribution

It proposes specific short peptide motifs made of prebiotically abundant amino acids, linking them to modern active sites and suggesting a common ancestral motif involved in phosphate manipulation.

Findings

Identified three main peptide motifs bound to Mg^{2+} ions in modern proteins.

Found these motifs are three times more frequent than expected by chance.

Suggested a common ancestral motif DGD as a precursor to active peptides.

Abstract

The issues we attempt to tackle here are what the first peptides did look like when they emerged on the primitive earth, and what simple catalytic activities they fulfilled. We conjecture that the early functional peptides were short (3 to 8 amino acids long), were made of those amino acids, Gly, Ala, Val and Asp, that are abundantly produced in many prebiotic synthesis experiments and observed in meteorites, and that the neutralization of Asp's negative charge is achieved by metal ions. We further assume that some traces of these prebiotic peptides still exist, in the form of active sites in present-day proteins. Searching these proteins for prebiotic peptide candidates led us to identify three main classes of motifs, bound mainly to Mg^{2+} ions: D(F/Y)DGD corresponding to the active site in RNA polymerases, DGD(G/A)D present in some kinds of mutases, and DAKVGDGD in dihydroxyacetone kinase. All three motifs contain a DGD submotif, which is suggested to be the common ancestor of all active peptides. Moreover, all three manipulate phosphate groups, which was probably a very important biological function in the very first stages of life. The statistical significance of our results is supported by the frequency of these motifs in today's proteins, which is three times higher than expected by chance, with a P-value of 3 10^{-2}. The implications of our findings in the context of the appearance of life and the possibility of an experimental validation are discussed.