SLIDE 1
Chemistry and Evolution at the Origin of Life Visions and Reality
Peter Schuster Institut für Theoretische Chemie und Molekulare Strukturbiologie der Universität Wien Madrid, Astrobiology Meeting 30.11.2001
SLIDE 2 From prebiotic chemistry to the first cellular
W
l d
c l a y s P r
r a m a b l e c a t a l y s t s S e l f
e p r
u c i n g m i n e r a l s S u r f a c e c a t a l y s i s ? R e p r
u c t i
i n t h r e e d i m e n s i
s ? T e m p l a t e c h e m i s t r y T e m p l a t e i n d u c e d r e a c t i
s L i g a t i
, c
p l e m e n t a r y s y n t h e s i s , m
e c u l a r c
y i n g , a u t
a t a l y s i s R N A p r e c u r s
s ? O r i g i n
t h e f i r s t R N A m
e c u l e s ? S t e r e
h e m i c a l p u r i t y , c h i r a l i t y ? N a t u r e
m
e c u l a r t e m p l a t e s ? N
i n s t r u c t e d p
y m e r s C
d e n s a t i
, p
y m e r i z a t i
, a g g r e g a t i
R a n d
i g
e p t i d e s , p r
e n
d s , l i p i d m e m b r a n e s , c a r b
y d r a t e s , . C
d e n s a t i
a g e n t ? P
y m e r i z a t i
m e c h a n i s m ? E x t r a t e r e s t r i a l
g a n i c m
e c u l e s H y d r
e n c y a n i d e , f
m a l d e h y d e , a m i n
c i d s , h y d r
i a c i d s , . M e t e r
i t e s , c
e t s , d u s t c l
d s S i m u l a t i
e x p e r i m e n t s H y d r
e n c y a n i d e , a m i n
c i d s h y d r
i a c i d s , p u r i n e b a s e s M i l e r
r e y , F i s c h e r
r
s c h , . P r i m
d i a l a t m
p h e r e ? H e a t i n g d u r i n g c
d e n s a t i
? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? S u l f u r b a s e d c h e m i s t r y S u r f a c e c a t a l y s i s
p y r i t e s H y d r
h e r m a l v e n t s R N A W
l d L i g a t i
, c l e a v a g e , e d i t i n g , r e p l i c a t i
, s e l e c t i
,
t i m i z a t i
R e a c t i
s w i t h n u c l e
i d e t e m p l a t e s R N A c a t a l y s i s S u l f u r m e t a b
i s m ? H e a t g r a d i e n t s a t d e e p s e a v
c O r g a n i c m
e c u l e s
World of clays Programable catalysts Self-reproducing minerals Surface catalysis ? Reproduction in three dimensions ? Template chemistry Template induced reactions Ligation, complementary synthesis, molecular copying, autocatalysis RNA precursors ? Origin of the first RNA molecules ? Stereochemical purity, chirality ? Nature of molecular templates ? Non instructed polymers Condensation, polymerization, aggregation Random oligopeptides, protenoids, lipid membranes, carbohydrates, ... Condensation agent ? Polymerization mechanism ? Extraterrestrial organic molecules Hydrogen cyanide, formaldehyde, amino acids, hydroxi acids,... Meterorites, comets, dust clouds Simulation experiments Hydrogen cyanide, amino acids hydroxi acids, purine bases Miller-Urey, Fischer-Tropsch, ... Primordial atmosphere ? Heating during condensation?
???? ???? ???? ???? ???? ????
Sulfur based chemistry Surface catalysis on pyrites Hydrothermal vents RNA World Ligation, cleavage, editing, replication, selection, optimization Reactions with nucleotide templates RNA catalysis Sulfur metabolism ? Heat gradients at deep sea volcanos ? Organic molecules
SLIDE 3
Origins of reactive organic molecules
Extraterrestrial organic molecules Hydrogen cyanide, formaldehyde, amino acids, hydroxi acids,... Meterorites, comets, dust clouds Heating during condensation? Simulation experiments Hydrogen cyanide, amino acids hydroxi acids, purine bases Miller-Urey, Fischer-Tropsch, ... Primordial atmosphere ? Sulfur based chemistry Surface catalysis on pyrites Hydrothermal vents Sulfur metabolism ? Heat gradients at deep sea volcanos ? Organic molecules
SLIDE 4
World of clays Programable catalysts Self-reproducing minerals Surface catalysis ? Reproduction in three dimensions ? Template chemistry Template induced reactions Ligation, complementary synthesis, molecular copying, autocatalysis RNA precursors ? Origin of the first RNA molecules ? Stereochemical purity, chirality ? Nature of molecular templates ?
Non instructed polymers Condensation, polymerization, aggregation Random oligopeptides, protenoids, lipid membranes, carbohydrates, ...
Condensation agent ? Polymerization mechanism ?
From small organic molecules to instructed polymers
SLIDE 5
???? ???? ???? ???? ???? ????
RNA World Ligation, cleavage, editing, replication, selection, optimization Reactions with nucleotide templates RNA catalysis
From an RNA world to the first living organisms
SLIDE 6
Three-dimensional structure of phenylalanyl-transfer-RNA
SLIDE 7 O CH2 OH O O P O O O
N1
O CH2 OH O P O O O
N2
O CH2 OH O P O O O
N3
O CH2 OH O P O O O
N4
N A U G C
k =
, , ,
3' - end 5' - end
Na Na Na Na
The chemical formula of RNA consisting of nucleobases, ribose rings, phosphate groups, and sodium counterions
SLIDE 8
2
Association Ligation Complex dissociation
Autocatalytic formation of a hexanucleotide template from two trinucleotides
SLIDE 9
Hydrogen bonds
Hydrogen bonding between nucleotide bases is the principle of template action of RNA and DNA
SLIDE 10 G G G G C C C G C C G C C G C C G C C G C C C C G G G G G C G C
Plus Strand Plus Strand Minus Strand Plus Strand Plus Strand Minus Strand
3' 3' 3' 3' 3' 5' 5' 5' 3' 3' 5' 5' 5' +
Complex Dissociation Synthesis Synthesis
Complementary replication as the simplest copying mechanism of RNA
SLIDE 11 G G G C C C G C C G C C C G C C C G C G G G G C
Plus Strand Plus Strand Minus Strand Plus Strand 3' 3' 3' 3' 5' 3' 5' 5' 5'
Point Mutation Insertion Deletion
GAA AA UCCCG GAAUCC A CGA GAA AA UCCCGUCCCG GAAUCCA
Mutations represent the mechanism of variation in nucleic acids
SLIDE 12
Space Sequence Concentration Master Sequence
The molecular quasispecies
SLIDE 13 U U U U U G G G G G G G G G G G G G G G G G A A A A A A A A A A C C C C C C C C C C C C C C C
Cleavage site
The "hammerhead" ribozyme
OH OH OH ppp 5' 5' 3' 3'
The smallest known catalytically active RNA molecules
SLIDE 14 Association Ligation Complex dissociation
E N T
+ +
E N
2 T
E N
= = Ar-
H N-
RMKQLEEKVYELLSKVA CLEYEVARLKKLGE
2 2
Ar-
RMKQLEEKVYELLSKV LEYEVARLKKLVEGE
2
T
= Ligation Site Ar Bn = = 4-Acetamidobenzoyl- Benzyl- Autocatalytic formation of a oligopetide template from two two precursor oligopeptides
SLIDE 15 L5 L5 R1 R1 M2 M2 K3 K3 Q4 Q4 E7 E7 E6 E6 L E K K
29 22 15 8
K K E L
8 15 22 29
L L L
12 19 26
V V V V
9 16 23 30
L E K
13 20 27
E C R E
11 18 25 32
Y10 A24 G31 S Y K
14 21 28
E R E
32 25 11
K E L
27 20 13
V30 V23 V16 V9 G A A Y
31 24 17 10
S Y K
14 21 28
L L L
26 19 12
Color code for amino acid residues
hydrophobic hydrophilic, neutral positively charged indifferent negatively charged
The
- helix wheel illustrating template action of
- ligopeptides by means of hydrophobic interaction
SLIDE 16
The three-dimensional structure of a short B-DNA double helix
SLIDE 17 Three-dimensional structure of the complex between the regulatory protein cro-repressor and the binding site on
SLIDE 18 + +
Replication: DNA 2 DNA → Transcription: DNA RNA → Metabolism
Food Waste
Nucleotides Amino Acids Lipids Carbohydrates Small Molecules
Translation: RNA Protein →
Protein mRNA
Ribosom
Information processing and metabolism in the DNA-RNA-protein world
SLIDE 19 Stock Solution Reaction Mixture
The flowreactor as a device for studies of evolution in vitro and in silico
SLIDE 20 250 500 750 1000 1250
Time
10 20 30 40 50
Average distance of the population from target Major changes in phenotypes Number of phenotypes in the relay series
Evolution in silico in the flow reactor
SLIDE 21
Genotype Space F i t n e s s
Start of Walk End of Walk Random Drift Periods Adaptive Periods
Evolution in genotype space sketched as a non-descending walk in a fitness landscape
SLIDE 22 yes
Selection Cycle
no
Genetic Diversity
Desired Properties ? ? ? Selection Amplification Diversification
Selection cycle used in applied molecular evolution to design molecules with predefined properties
SLIDE 23 Retention of binders Elution of binders C h r
a t
r a p h i c c
u m n
The SELEX technique for the evolutionary design of aptamers
SLIDE 24 Stage I: Independent Competing Replicators Stage II: Functionally Coupled Replicators Stage III: New Unit of Selection Stage IV = I: Independent Competing Units Parasite Parasite
The hypercycle model of major evolutionary transitions
SLIDE 25
Coworkers
Walter Fontana, Santa Fe Institute, NM Christian Reidys, Christian Forst, Los Alamos National Laboratory, NM Peter Stadler, Universität Wien, AT, Ivo L.Hofacker Christoph Flamm Bärbel Stadler, Andreas Wernitznig, Universität Wien, AT, Stefanie Widder, Ulrike Mückstein, Stefan Wuchty Ulrike Göbel, Institut für Molekulare Biotechnologie, Jena, GE, Walter Grüner, Stefan Kopp, Jaqueline Weber
