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Basic Questions about the Origin of Life O N THE G ENETIC C ODE

Basic Questions about the Origin of Life O N THE G ENETIC C ODE. HOW DID TRANSLATION OCCUR ?. A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds :

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Basic Questions about the Origin of Life O N THE G ENETIC C ODE

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  1. Basic Questions about the Origin of LifeONTHE GENETIC CODE HOW DID TRANSLATION OCCUR ? A ‘MOLECULAR DEAL’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds : Too low mobility and irreversible precipitation of peptides. Too high mobility and infinite dilution of nucleic acids. A proposition by Peter Strazewski, Lyon

  2. Angewandte Chemie International Edition in English, 1972, 11, 798-830 1972

  3. Angewandte Chemie International Edition in English, 1981, 20, 500-520

  4. Angewandte Chemie International Edition in English, 1981, 20, 500-520

  5. Journal of Molecular Evolution, 1989, 29, 465-474 A) 3'-aminoacyl-RNA B) Uncoded peptidyl transfer C) mRNA-encoded peptidyl transfer (PT) D) ribosome-catalysed and mRNA-encoded PT

  6. Eörs Szathmáry in: «Evolution: from Cosmogenesis to Biogenesis» (B. Lukacs et al. eds.) KFKI1990, 50/C, 77-83

  7. Early Middle Late A1-AMP A3-tRNA3 A3-tRNA3 + A2-A3-tRNA3 + A1-A2-tRNA2 + A1-A2-tRNA2 A1-A2-A3-tRNA3 === === III Template RNA Origin of genetically encoded protein synthesis : A model based on selection for RNA peptidation Origin of Life and Evolution of the Biosphere, 1991, 21, 165-176 Jeffrey Tze-Fei Wong A) 3'-aminoacyl-AMP + 3'-peptidyl-RNA B) Uncoded peptidyl transfer C) mRNA-encoded peptidyl transfer

  8. On the origin of protein synthesis : A speculative model based on hairpin RNA structures Journal of Theoretical Biology, 1994, 171, 303-8 Massimo Di Giulio A) Uncoded peptidyl transfer through (bulged) double-strand formation between 3'-aminoacyl-RNA hairpin (+) RNA hairpin (+) 5'-aminoacyl-RNA hairpin => 5'-dipeptidyl-RNA hairpin (-) 5'-aminoacyl-RNA hairpin (-) 5'-dipeptidyl-RNA hairpin (-) B) Stabilisation of cruciforms between the above hairpins through mRNA C) mRNA-encoded peptidyl transfer between 3'-aminoacyl and 3'-peptidyl-tRNAs D) rRNA-catalysed peptidyl transfer

  9. 1994

  10. 1994 (reproduced from 1987)

  11. Experimentally taken care of by: John D. Sutherland, Manchester, UK Prebiotic Aminoacylation of Nucleotides Chemistry & Biodiversity2004, 1, 203-246

  12. More contributions to the origin of tRNA as a basis for the appearance of the genetic code and translation(and replication) : Manfred Eigen, Peter Schuster, Ruthild Winkler 1972, 1981, 1989 Jeffrey Tze-Fei Wong 1975-2006, ... Massimio Di Giulio 1989-2006, ... Toby Gibson & Angus Lamond 1990 Tobias Dick & Wolfgang Schamel 1995 Nancy Maizels & Alun Weiner 1987-1999 ... Importance of compartmentalisation and the matrix effect : William Hargreaves, Sean Mulvihill, David Deamer et al. 1977- ... Pier Luigi Luisi, Peter Walde, Evelyne Blöchliger, Markus Blocher et al. 1998-2004 Jack Szostak, Martin Hanczyc 2001- ...

  13. MAJOR PLAYERS NUCLEIC ACIDS replicate primary sequence PROTEINS recognise SUGARS recognise LIPIDS replicate shape HYDROPHILES AMPHIPHILES

  14. hydrophilic A-RNA hairpin-3'-oligopeptide lipophilic A-RNA a-helix ACCA stack helix dipole shallow groove 5’-RNA-3’-(Ala)21 deep groove UUCG loop deep groove UUCG loop ACCA stack a-helix shallow groove shallow groove

  15. hydrophilic A-RNA hairpin-3'-oligopeptide lipophilic A-RNA b-strand ACCA stack 5’-RNA-3’-(Ala)21 UUCG loop shallow groove deep groove

  16. love you both MOLECULAR DEAL N.A. to P.P.: « I'll help you to stay in solution, if you help me not to get washed away » P.P. to N.A.: « I'll help you to stick around, if you help me to hold sufficient distance to my buddies »

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