a ‘m olecular d eal ’ between lipophilic peptides and hydrophilic nucleic acids helped to...

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A ‘MOLECULAR DEALbetween 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. Basic Questions about the Origin of Life ON THE GENETIC CODE A proposition by Peter Strazewski, Lyon

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Page 1: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

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.

Basic Questions about the Origin of Life

ON THE GENETIC CODE

A proposition by Peter Strazewski, Lyon

Page 2: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

Angewandte Chemie

International Edition in English,

1972, 11, 798-8301972

Page 3: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

Angewandte Chemie

International Edition in English,

1981, 20, 500-520

Page 4: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

Angewandte Chemie

International Edition in English,

1981, 20, 500-520

Page 5: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

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

Page 6: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

Eörs Szathmáry in:

«Evolution: from

Cosmogenesis to Biogenesis»

(B. Lukacs et al. eds.)

KFKI 1990, 50/C, 77-83

Page 7: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

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

A) 3'-aminoacyl-AMP + 3'-peptidyl-RNA

B) Uncoded peptidyl transfer

C) mRNA-encoded peptidyl transfer

Jeffrey Tze-Fei Wong

Early Middle Late

A1-AMP A3-tRNA3 A3-tRNA3

+ A2-A3-tRNA3 + A1-A2-tRNA2 + A1-A2-tRNA2

A1-A2-A3-tRNA3

===

===

TemplateRNA

III

Page 8: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

On the origin of protein synthesis : A speculative model based on hairpin RNA structures

Journal of

Theoretical Biology,

1994, 171, 303-8

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

Massimo Di Giulio

Page 9: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

1994

Page 10: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

1994 (reproduced from 1987)

Page 11: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds
Page 12: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

Experimentally taken care of by:

John D. Sutherland, Manchester, UK

Prebiotic Aminoacylation of Nucleotides

Chemistry & Biodiversity 2004, 1, 203-246

Page 13: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

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, 1989Jeffrey Tze-Fei Wong 1975-2006, ...Massimio Di Giulio 1989-2006, ...Toby Gibson & Angus Lamond 1990Tobias Dick & Wolfgang Schamel 1995Nancy 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- ...

Page 14: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

MAJOR PLAYERS

NUCLEICACIDS

replicateprimary

sequence

PROTEINS

recognise

LIPIDS

replicateshape

SUGARS

recognise

HYDROPHILES AMPHIPHILES

Page 15: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

A-RNA hairpin-3'-oligopeptidehydrophilic lipophilic

shallowgroove

deepgroove

shallowgroove

-helixA-RNA

5’-RNA-3’-(Ala)21

UUCGloop

ACCAstack

ACCAstack

UUCGloop

deepgroove

-helix

helixdipole

shallowgroove

Page 16: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

shallowgroove

deepgroove

A-RNA hairpin-3'-oligopeptidehydrophilic lipophilic

-strandA-RNA

5’-RNA-3’-(Ala)21UUCGloop

ACCAstack

Page 17: A ‘M OLECULAR D EAL ’ between lipophilic peptides and hydrophilic nucleic acids helped to overcome the major selection obstacle of each class of compounds

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 »

love you both