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Basic questions about the Origin of Life Erice 3rd October 2006

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					      Basic Questions about the Origin of Life


     ON THE GENETIC CODE


 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
    Angewandte Chemie
International Edition in English,
   1972, 11, 798-830
    1972
    Angewandte Chemie
International Edition in English,
   1981, 20, 500-520
    Angewandte Chemie
International Edition in English,
   1981, 20, 500-520
               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
    Eörs Szathmáry in:
     «Evolution: from
Cosmogenesis to Biogenesis»
   (B. Lukacs et al. eds.)
KFKI 1990, 50/C, 77-83
            Origin of Life and
       Evolution of the Biosphere,
          1991, 21, 165-176
     Origin of genetically encoded protein synthesis :
     A model based on selection for RNA peptidation

        Jeffrey Tze-Fei Wong

                                            Early         Middle             Late

                                          A1-AMP         A3-tRNA3        A3-tRNA3 ===
A) 3'-aminoacyl-AMP +                                       III
                                     + A2-A3-tRNA3 + A1-A2-tRNA2     + A1-A2-tRNA2 ===
   3'-peptidyl-RNA
B) Uncoded peptidyl transfer
                                                                             Template
                                                                                RNA
C) mRNA-encoded
   peptidyl transfer
                                                    A1-A2-A3-tRNA3
                  Journal of
             Theoretical Biology,
             1994, 171, 303-8
        On the origin of protein synthesis : A speculative
        model based on hairpin RNA structures

          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
1994
       1994
(reproduced from 1987)
    Experimentally taken care of by:
 John D. Sutherland, Manchester, UK
 Prebiotic Aminoacylation of Nucleotides
Chemistry & Biodiversity 2004, 1, 203-246
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- ...
              MAJOR PLAYERS


              NUCLEIC     PROTEINS
               ACIDS
                          recognise
              replicate
               primary
              sequence




              SUGARS      LIPIDS

              recognise   replicate
                           shape


HYDROPHILES                      AMPHIPHILES
 hydrophilic       A-RNA hairpin-3'-oligopeptide              lipophilic
 A-RNA
                   ACCA
                                                              a-helix
                   stack            helix
                                   dipole




shallow
groove

                                             5’-RNA-3’-(Ala)21

UUCG      deep
 loop     groove
                                                         deep
                                            UUCG         groove
                                                                   ACCA
                                             loop                  stack




                                                                           a-helix
shallow
groove                                              shallow
                                                    groove
hydrophilic       A-RNA hairpin-3'-oligopeptide   lipophilic
A-RNA                                             b-strand
              ACCA
              stack




     UUCG
      loop
                                         5’-RNA-3’-(Ala)21




                      shallow
                      groove
        deep
        groove
             MOLECULAR DEAL

     N.A. to P.P.: « I'll help you to stay in solution,
       if you help me not to get washed away »

                                       love you both




       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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