title: The first peptides: the evolutionary transition between prebiotic amino acids and early proteins.
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 (3-8 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 x 10(-2). The implications of our findings in the context of the appearance of life and the possibility of an experimental validation are discussed.
authors.affiliation: Centrum Wiskunde and Informatica, Kruislaan 413, 1098 SJ Amsterdam, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van der Gulik
authors.forename: Serge
authors.initials: S
authors.lastname: Massar
authors.forename: Dimitri
authors.initials: D
authors.lastname: Gilis
authors.forename: Harry
authors.initials: H
authors.lastname: Buhrman
authors.forename: Marianne
authors.initials: M
authors.lastname: Rooman
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D019418:Evolution, Chemical; D008954:Models, Biological; D008958:Models, Molecular; D000069497:Origin of Life; D010455:Peptides / Q000737:chemistry*; D056692:Prebiotics; D054928:Validation Studies as Topic
chemical_list: D000596:Amino Acids; D010455:Peptides; D056692:Prebiotics