Open questions in origin of life: experimental studies on the origin of nucleic acids and proteins with specific and functional sequences by a chemical synthetic biology approach.
In this mini-review we present some experimental approaches to the important issue in the origin of life, namely the origin of nucleic acids and proteins with specific and functional sequences. The formation of macromolecules on prebiotic Earth faces practical and conceptual difficulties. From the chemical viewpoint, macromolecules are formed by chemical pathways leading to the condensation of building blocks (amino acids, or nucleotides) in long-chain copolymers (proteins and nucleic acids, respectively). The second difficulty deals with a conceptual problem, namely with the emergence of specific sequences among a vast array of possible ones, the huge "sequence space", leading to the question "why these macromolecules, and not the others?" We have recently addressed these questions by using a chemical synthetic biology approach. In particular, we have tested the catalytic activity of small peptides, like Ser-His, with respect to peptide- and nucleotides-condensation, as a realistic model of primitive organocatalysis. We have also set up a strategy for exploring the sequence space of random proteins and RNAs (the so-called "never born biopolymer" project) with respect to the production of folded structures. Being still far from solved, the main aspects of these "open questions" are discussed here, by commenting on recent results obtained in our groups and by providing a unifying view on the problem and possible solutions. In particular, we propose a general scenario for macromolecule formation via fragment-condensation, as a scheme for the emergence of specific sequences based on molecular growth and selection.
Sciences Department, University of Roma Tre; Viale Guglielmo Marconi 446, 00146 Rome, Italy ; MIT Media Lab, Departments of Brain and Cognitive Sciences and Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA ; These Authors are listed in alphabetic order and contributed equally to the work.
Katarzyna
K
Adamala
Sciences Department, University of Roma Tre; Viale Guglielmo Marconi 446, 00146 Rome, Italy ; Department of Bionanoscience, Kavli Institute of Nanoscience Delft University of Technology Lorentzweg 1, 2628 CJ, Delft, The Netherlands ; These Authors are listed in alphabetic order and contributed equally to the work.
Fabrizio
F
Anella
Sciences Department, University of Roma Tre; Viale Guglielmo Marconi 446, 00146 Rome, Italy ; FLinT Center, Institut for Fysik, Kemi og Farmaci (IFKF), University of Southern Denmark; Campusvej 55, 5230 Odense, Denmark ; These Authors are listed in alphabetic order and contributed equally to the work.
Rafal
R
Wieczorek
Sciences Department, University of Roma Tre; Viale Guglielmo Marconi 446, 00146 Rome, Italy.
Pasquale
P
Stano
Sciences Department, University of Roma Tre; Viale Guglielmo Marconi 446, 00146 Rome, Italy.
Cristiano
C
Chiarabelli
Sciences Department, University of Roma Tre; Viale Guglielmo Marconi 446, 00146 Rome, Italy.
Pier Luigi
PL
Luisi
Ser-His; fragment condensation; organocatalysis; origin of life; random RNA; random proteins; sequence space