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Looking for the Cradle of Life

Looking for the Cradle of Life. Sergio Branciamore DBAG- University of Florence - Italy. Biological approach. Chemical approach. Origin of Life: a multidisciplinary problem. Theoretical approach. Erwin Schr ö dinger. “What is Life ?”, 1944. “What is Life today ?”.

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Looking for the Cradle of Life

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  1. Looking for the Cradle of Life Sergio Branciamore DBAG- University of Florence - Italy

  2. Biological approach Chemical approach Origin of Life: a multidisciplinary problem Theoretical approach

  3. Erwin Schrödinger “What isLife ?”, 1944

  4. “What isLife today ?”

  5. Pathways of supersystem evolution metabolism MB boundary MT MBT template BT INFRABIOLOGICAL SYSTEMS

  6. The Transition from the RNA to the DNA World

  7. The recipe of rising life • Synthesis and accumulation of precursors (nucleotides) • Joining of precursors into larger molecules • Protection of biomolecules from degradation • Expression of “biological” potentiality of the informational molecules

  8. “The Primordial Soup” A.I. Oparin (~1920) - J.B.S. Haldane (~1930) Classical research: Aqueous Solution Chemistry (primordial oceans) S.L. Miller (1953)

  9. Main problems of prebiotic chemistry in aqueous solution: • Dilution: concentration of reactants • Building blocks synthesis • Polymerization: Hydrolysis and not polymerization occurs !!

  10. H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O

  11. Main problems of prebiotic chemistry in aqueous solution: • Dilution: concentration of reactants • Building blocks synthesis • Polymerization: Hydrolysis and not polymerization occurs !! • Polymers eventually formed are very susceptible to degradation (environmental persistence)

  12. Looking for the Suitable Environment for the Emergence of Life

  13. Possible Physical Settings It is necessary a protected confined environment where the primordial genetic molecule, could originate and express its biological potential to self-replicate and evolve The snowball hypothesis (L.E. Orgel, A.V.Vlassov) Hydrothermal vent & pyrite (G. Wächtershäuser M.J. Russel) Mineral environment

  14. The “Mineral Honeycomb” “. . . clays and other minerals were necessary to: 1) Concentrate the organics present in a dilute ocean by adsorption; 2) Protect these organics from destruction by U.V. light; 3) Catalyze the polymerization of adsorbed organics . . . ” J.D. Bernal (1951)

  15. Heat-driven molecular accumulation in hydrothermal pores. Section through aragonite (CaCO3) from the submarine hydrothermal vent field at Lost City The mechanism of accumulation is driven by heat in a twofold way. Thermal convection shuttles the molecules vertically up and down and thermophoresis pushes the molecules horizontally to the right. The result is a strong molecular accumulation from the top to the bottom (linear concentration color scale).

  16. Synthesis of building blocks • Formation of sugar-phosphates in the presence of mineral particles, Pitsch et al., OLEB (1995) • Stabilization of ribose in the presence of borate minerals, Ricardo et al., Science (2004) • Synthesis of Nucleobases by Formamide in the Presence of Montmorillonite, Saladino et al., ChemBioChem (2004)

  17. Polymerization of precursors into larger molecules Montmorillonite catalyzes the formation of oligonucleotides up to 50-mer long Ertem and Ferris Nature (1996) Ferris et al. Nature (1996) G T C C C T A \

  18. Protection & Expression of Nucleic Acids Adsorbed on Minerals

  19. Hairpin Ribozyme 16S RNA ssRNA Viroid RNA-Clay Complexes minerals RNA-mineral Complexes

  20. Could Mineral-RNA Complexes Perform Enzymatic Reaction?? Hammerhead Ribozymes Hairpin Ribozymes

  21. HAMMERHEAD 3’ 3’ 5’ 5’ U U A A 53 53 392 392 U U A A C C G G U U A A Cleavage Site III III C C G G C C G G A A U U A A C C A A U U G G G G A A C C A A G G G G C C A A C C C C C C U U G G G G A A A A C C G G C C C C G G U U G G G G A A G G C C C C U U G G C C U U U U A A A A A A A A C C U U I I II II A A G G G G A A U U Viroids Structural characteristics: • Single stranded, circular, 250-400 nt long • Mostly, self-complementary (double helix) • Not coding • “Nude” (without capside) • Replication by rolling circle • Smallest and simplest autonomous infective agents HAMMERHEAD Cleavage Site Viroids Could be Relics of the RNA World

  22. Interactions of Hammerhead and Hairpin Ribozymes with Clay Particles • Increase self-cleavage kinetics of ribozymes (“natural prebiotic chaperon”); • Protect RNA from degradation. free solution Kobs= 0.027 min-1 F∞= 0.55 + montmorillonite Kobs= 0.343 min-1 F∞= 0.58

  23. UV irradiation of ADHR1 hairpin ribozymes in the presence of Montmorillonite UV254 nm Self-cleavage The UV inactivation of hairpin ribozyme is strongly reduced by the presence of clay minerals

  24. Early replication is still a problem: Eigen’s paradox (1971) • Early replication must have been error-prone

  25. Quasispecie

  26. Error catastrophe Eigen’s paradox No genome without enzymes, and no enzyme without genomes

  27. Early replication is still a problem: Eigen’s paradox (1971) • Early replication must have been error-prone • Error threshold sets the limit of maximal genome size to <100 nucleotides • Not enough for several genes • Unlinked genes will compete • Genome collapses • Resolution???

  28. autocatalysis heterocatalytic aid HYPERCYCLE MODEL short circuit R6 parasite

  29. Population structure is necessary! Good-bye to the well-stirred flow reactor !!! The evolutionary processes need adhesion to surface or compartmentation

  30. The stochastic corrector model

  31. Hypercycle in a (mineral) surface Hypercycles (with more than 4 members) spiral on the surface and resist to some type of parasites

  32. R1 Metabolism R2 R4 R3 The metabolic model

  33. metabolism SEM image of etch-pit network near the surface of a weathered Shap alkali feldspar. (Scale bar 20 µm.) Mineral environment Pore ribozymes nucleotides resources

  34. Evolution of an RNA population in a network of inorganic compartments

  35. Phosphate (from apatite) N-Base Ribose

  36. RADIATION Interaction Protection Evolution

  37. Conclusions The formation of a “close” association between prebiotic genetic molecules – whatever they were – and mineral surfaces could have represented a crucial step in the origin, persistence and activity of genetic material in primeval terrestrial habitats, opening the way to the biochemical evolution on Earth suggesting the possibility of a….. Mineral-Mediated Life

  38. 2’ 2’ 5’ OH 5’ OH P P 3’ 3’ Infective Viroid Rolling Circle Replicative cycle

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