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
Extraterrestrial organic Simulation experiments molecules Hydrogen cyanide, amino acids Primordial atmosphere ? Heating during condensation? Hydrogen cyanide, formaldehyde, hydroxi acids, purine bases amino acids, hydroxi acids,... Miller-Urey, Fischer-Tropsch, ... Meterorites, comets, dust clouds Sulfur based chemistry Sulfur metabolism ? World of clays Surface catalysis ? Organic molecules Programable catalysts Surface catalysis on pyrites Heat gradients at deep sea volcanos ? Reproduction in three dimensions ? Hydrothermal vents Self-reproducing minerals Non instructed polymers Template chemistry Nature of molecular templates ? Condensation agent ? Random oligopeptides, protenoids, RNA precursors ? Template induced reactions lipid membranes, carbohydrates, ... d e o c g n s a t i o n n t ? H r e t a r t x E l R e n a t i n g d u r i ? r c e t r a l u e p l m f o e r m l s s e t u e c u r o a r s s ? i N a e r t i t e M . , s d i c a x r o r d y h , s d i c e o d s d u o l c t s u r , s t e m o c , s e t i a o o r d y H s e l u c e l m g c i n a g r o l a i o e n a i m a , e d y h e d l m n r o f , e d n a y c p o A i e s n o i d m r e n s i o n s e h ? u ? R e p r o d c t t i o n i n T s y t a l p m e T r t s i m e h N c e i e c m p l a t e a n e r d e c u d t i a m a b l e c t r a l y s t s S a g l o R W o r l d f o c l a y s r e P f c e r a l s S u f a e i c a t a l y s - n r m r p r o d u c i e n g d r y h s x d i c a i a n o , c i d s a b e o n i r u p r n d e e r i m e n t s p x e H y o i i m a , e d n g a y c n e s e s d y r i t e s H y r o t h e r m s a l p n v a g r O c l o v e o a t a l y s i s e a t g r a d i e n p e e e d t a s t a H n m t s S u l f u r e ? t a b o l i s m i n M r h , . P r i m o d s i a l a t m o s c p h , i l e r - U r e y o F i s c h r - T r p e i s y S u r f a c e c e s l u c e l o m c t i r r e ? S u l f u m b a s e d c h e o r t o p t i d e s , p r o t e n i p e e n a r b m m d d p i , s e o , p u c t e d o t l y m e r s r s g d i l o m o n n a N o n i s i n a t i o n a e t n ? c l u m i S a s g e t o d b r d a h a r y n s , o C . e l t d i g a i L N o m A R t s r i f o l n r e i t c a e R n o i o s w e i R N l u c e t a c i l p s h t a r y s y n h n e s i o , m o t e e n L i g a t i o , m c o m p l e l c t r a l y s i s O i a g i n o f t c u y l a r c o p i o n g , a u t r S W ? h e m i h a l p ? ? ? o ? ? ? a r i u r i t y , c c l A N R e s ? t e r i e ? c y t ? ? ? ? ? ? ? m y l o p , n o i t ? s ? ? ? a i e m r i z a t i o n e m c h a n i s m ? e y r g i z a t o n , a g l r e g a t i o n P o ? s n o s e l e c t i n , , e p t i m i , g a a n , c l e a v g n e , e d i t i z o t p l i a t e s A c m a t a l y i s C d o n o n u c l e t t i h d e n t e o Origin of the first RNA molecules ? Polymerization mechanism ? Ligation, complementary synthesis, Condensation, polymerization, Stereochemical purity, chirality ? molecular copying, autocatalysis aggregation RNA World Reactions with nucleotide templates RNA catalysis Ligation, cleavage, editing, replication, selection, optimization ???? ???? ???? ???? ???? ???? From prebiotic chemistry to the first cellular organisms
Heating during condensation? Primordial atmosphere ? Extraterrestrial organic Simulation experiments molecules Hydrogen cyanide, amino acids Hydrogen cyanide, formaldehyde, hydroxi acids, purine bases amino acids, hydroxi acids,... Miller-Urey, Fischer-Tropsch, ... Meterorites, comets, dust clouds Sulfur based chemistry Organic molecules Surface catalysis on pyrites Hydrothermal vents Sulfur metabolism ? Heat gradients at deep sea volcanos ? Origins of reactive organic molecules
Surface catalysis ? Reproduction in three dimensions ? World of clays Programable catalysts Condensation agent ? Self-reproducing minerals Polymerization mechanism ? Non instructed polymers Template chemistry Random oligopeptides, protenoids, Template induced reactions lipid membranes, carbohydrates, ... Ligation, complementary synthesis, Condensation, polymerization, aggregation molecular copying, autocatalysis Nature of molecular templates ? RNA precursors ? Origin of the first RNA molecules ? From small organic molecules to Stereochemical purity, chirality ? instructed polymers
RNA World Reactions with nucleotide templates RNA catalysis Ligation, cleavage, editing, replication, selection, optimization ???? ???? ???? ???? ???? ???? From an RNA world to the first living organisms
Three-dimensional structure of phenylalanyl-transfer-RNA
5' - end The chemical formula of RNA N 1 consisting of nucleobases, O CH 2 O ribose rings, phosphate groups, and sodium counterions N A U G C k = , , , OH O N 2 O P O CH 2 O Na O O OH N 3 O P O CH 2 O Na O O OH N 4 O P O CH 2 O Na O O OH 3' - end O P O Na O
Association Ligation Complex dissociation Autocatalytic formation of a hexanucleotide template from two trinucleotides 2
Hydrogen bonds Hydrogen bonding between nucleotide bases is the principle of template action of RNA and DNA
5' 3' Plus Strand G C C C G Synthesis 5' 3' Plus Strand G C C C G C G 3' Synthesis 5' 3' Plus Strand G C C C G Minus Strand C G G G C 5' 3' Complex Dissociation 3' 5' Plus Strand G C C C G Complementary replication as + the simplest copying 5' 3' mechanism of RNA Minus Strand C G G G C
5' 3' Plus Strand G C C C G 5' 3' GAA UCCCG AA GAA UCCCGUCCCG AA Plus Strand G C C C G Insertion C 3' G 5' 3' Minus Strand G G C G G C GAAUCCA GAAUCC CGA A 3' 5' Deletion Plus Strand G C C C G C Point Mutation Mutations represent the mechanism of variation in nucleic acids
Master Sequence Concentration Sequence Space The molecular quasispecies
OH 5' 3' OH U A G C Cleavage site C G G C U A A C G G U C G C C OH 3' A G C ppp 5' C A G C G G A A G G C C C U C C G G A G G A A G U The "hammerhead" ribozyme The smallest known catalytically active RNA molecules
E N T + + E = Ar- RMKQLEEKVYELLSKVA -CO-S-Bn Association N = CLEYEVARLKKLGE H N- -CO-NH 2 2 E N T = Ar- RMKQLEEKVYELLSKV LEYEVARLKKLVEGE -CO-NH Ligation 2 Ligation Site 4-Acetamidobenzoyl- Ar = Complex dissociation Benzyl- = Bn 2 T Autocatalytic formation of a oligopetide template from two two precursor oligopeptides
L 29 E K E G 22 27 32 31 K E R A 15 20 25 24 K L A 8 13 V 30 17 E Y L 11 V 23 10 26 R 1 E 6 L V 16 19 Q 4 K 3 L 12 V 9 M 2 L 5 E 7 E 7 S S 14 14 Y Y 21 21 K K 28 28 M 2 L 5 V L 9 12 K 3 Q 4 V L 16 19 E 6 R 1 V L E Y 10 23 26 11 V C 30 L 18 K 13 8 R A 24 E 25 K 20 15 E Color code for amino G 31 K 32 E 27 22 acid residues L 29 hydrophobic indifferent hydrophilic, neutral The � -helix wheel illustrating template action of positively charged oligopeptides by means of hydrophobic interaction negatively charged
The three-dimensional structure of a short B-DNA double helix
Three-dimensional structure of the complex between the regulatory protein cro-repressor and the binding site on � -phage B-DNA
Replication: → DNA 2 DNA + + Transcription: Food RNA Nucleotides → Amino Acids Metabolism Lipids DNA Carbohydrates Small Molecules Waste Ribosom Protein mRNA → Translation: RNA Protein Information processing and metabolism in the DNA-RNA-protein world
Stock Solution Reaction Mixture The flowreactor as a device for studies of evolution in vitro and in silico
Major changes in phenotypes 50 Average distance of the population from target Number of phenotypes in the relay series 40 30 20 10 0 0 250 500 750 1000 1250 Time Evolution in silico in the flow reactor
End of Walk Adaptive Periods s s e n t i F Random Drift Periods Start of Walk Genotype Space Evolution in genotype space sketched as a non-descending walk in a fitness landscape
Amplification Diversification Genetic Diversity Selection Cycle Selection Desired Properties ? ? ? no Selection cycle used in yes applied molecular evolution to design molecules with predefined properties
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