Chemistry and Evolution at the Origin of Life. Visions and Reality

Transcription

1 hemistry and Evolution at the rigin of Life Visions and Reality Peter Schuster Institut für Theoretische hemie und Molekulare Strukturbiologie der Universität Wien Madrid, Astrobiology Meeting

2 H eatingduring condensation EHydro? molecul fxtraterestria gencyanide, lorganic es ormaldehyde, Hydrogencya Simulation hydroxiaci experiments nide,aminoac ds,purinebase Priids s mordialatmo sphere? amimete noacids, rorites,comets hydr oxiacids,.,dustclouds Miler-Urey,F ischer-tropsc h,. Sur facecatalysis? Worldofc lays Sulfurb rgani asedchemistr cmolecules Su y lfurmetabolis m? Reprod uctioninthre edimensions? PSe rogramablec lf-reproducing minerals atalysts Surfacecata Hydrot lysisonpyrite hermalvents Heas tgradientsat depseavolc Noninstru ctedpolymers Nat RNureofmolecu Aprecursors lartemplates? Te Templateche mplateinduced reactions mistry Rl andomoligop ipidmembrane eptides, protencarbohydrat.onoids, es, densationag ent? rigin Ster ofthefirstrn eochemicalpu Amolecules rity,chirality? Ligatimolec ularcopying, on,complemen tarysynthesis, autocatalysis ondensation ag, regation polymerizatio Pol n, ymerizationm echanism? RNAWorld Ligatio Reactionsw n,cleavage,ed ithnucleotide NAcatalysis iting, templates? replication?,selection,opt? imization? Heating during condensation? 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? Surface catalysis? World of clays Sulfur based chemistry rganic molecules Sulfur metabolism? Reproduction in three dimensions? Programable catalysts Self-reproducing minerals Surface catalysis on pyrites Hydrothermal vents Heat gradients at deep sea volcanos? Nature of molecular templates? RNA precursors? rigin of the first RNA molecules? Stereochemical purity, chirality? Template chemistry Template induced reactions Ligation, complementary synthesis, molecular copying, autocatalysis Non instructed polymers Random oligopeptides, protenoids, lipid membranes, carbohydrates,... ondensation, polymerization, aggregation ondensation agent? Polymerization mechanism? RNA World Reactions with nucleotide templates RNA catalysis Ligation, cleavage, editing, replication, selection, optimization From prebiotic chemistry to the first cellular organisms????????????????????????

3 Heating during condensation? Primordial atmosphere? 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,... Sulfur based chemistry rganic molecules Surface catalysis on pyrites Hydrothermal vents Sulfur metabolism? Heat gradients at deep sea volcanos? rigins of reactive organic molecules

4 Surface catalysis? Reproduction in three dimensions? World of clays Programable catalysts Self-reproducing minerals ondensation agent? Polymerization mechanism? Template chemistry Template induced reactions Ligation, complementary synthesis, molecular copying, autocatalysis Non instructed polymers Random oligopeptides, protenoids, lipid membranes, carbohydrates,... ondensation, polymerization, aggregation Nature of molecular templates? RNA precursors? rigin of the first RNA molecules? Stereochemical purity, chirality? From small organic molecules to instructed polymers

5 RNA World Reactions with nucleotide templates RNA catalysis Ligation, cleavage, editing, replication, selection, optimization???????????????????????? From an RNA world to the first living organisms

6 Three-dimensional structure of phenylalanyl-transfer-rna

7 5' - end H 2 H N 1 N k = A, U,, The chemical formula of RNA consisting of nucleobases, ribose rings, phosphate groups, and sodium counterions P H 2 N 2 Na H P H 2 N 3 Na H P H 2 N 4 Na H P - end Na

8 Association Ligation omplex dissociation 2 Autocatalytic formation of a hexanucleotide template from two trinucleotides

9 Hydrogen bonding between nucleotide bases is the principle of template action of RNA and DNA Hydrogen bonds

10 5' Plus Strand Synthesis 5' Plus Strand Synthesis 5' Plus Strand Minus Strand 5' omplex Dissociation 5' Plus Strand 5' Minus Strand + omplementary replication as the simplest copying mechanism of RNA

11 5' Plus Strand 5' AAUAA AAUUAA Plus Strand Insertion 5' Minus Strand AAUAA AAUA Plus Strand 5' Deletion Point Mutation Mutations represent the mechanism of variation in nucleic acids

12 Master Sequence Space Sequence oncentration The molecular quasispecies

13 H U A H 5' leavage site A U A A U H A A ppp 5' A A A U U A The "hammerhead" ribozyme The smallest known catalytically active RNA molecules

14 Association Ligation E + N + T E N E N = = Ar-RMKQLEEKVYELLSKVA--S-Bn HN-LEYEVARLKKLE--NH 2 2 T = Ar-RMKQLEEKVYELLSKV LEYEVARLKKLVEE--NH 2 Ligation Site omplex dissociation 2 T Ar = 4-Acetamidobenzoyl- Bn = Benzyl- Autocatalytic formation of a oligopetide template from two two precursor oligopeptides

15 E R E Q L E K K R 1 L L L V 30 V 23 V 16 V 9 K E L E A A Y K L 5 M 2 S Y K E 7 M 2 L 5 E 7 S Y K K 3 Y 10 A E 6 L E K V V V V L L L R 1 K K E L Q 4 E R E olor code for amino acid residues hydrophobic indifferent The -helix wheel illustrating template action of oligopeptides by means of hydrophobic interaction hydrophilic, neutral positively charged negatively charged

16 The three-dimensional structure of a short B-DNA double helix

17 Three-dimensional structure of the complex between the regulatory protein cro-repressor and the binding site on -phage B-DNA

18 Replication: DNA 2 DNA + Transcription: DNA RNA Nucleotides Amino Acids Lipids arbohydrates Small Molecules Metabolism Food Waste Ribosom mrna Protein Translation: RNA Protein Information processing and metabolism in the DNA-RNA-protein world

19 Stock Solution Reaction Mixture The flowreactor as a device for studies of evolution in vitro and in silico

20 Major changes in phenotypes Number of phenotypes in the relay series Time Evolution in silico in the flow reactor Average distance of the population from target

21 Adaptive Periods End of Walk Fitness Random Drift Periods Start of Walk enotype Space Evolution in genotype space sketched as a non-descending walk in a fitness landscape

22 Amplification Diversification Selection ycle enetic Diversity Selection Selection cycle used in applied molecular evolution to design molecules with predefined properties no Desired Properties??? yes

23 Retention of binders Elution of binders hromatographic column The SELEX technique for the evolutionary design of aptamers

24 Stage I: Independent ompeting Replicators Stage II: Functionally oupled Replicators Parasite Stage III: New Unit of Selection Parasite The hypercycle model of major evolutionary transitions Stage IV = I: Independent ompeting Units

25 oworkers Walter Fontana, Santa Fe Institute, NM hristian Reidys, hristian Forst, Los Alamos National Laboratory, NM Peter Stadler, Universität Wien, AT, Ivo L.Hofacker hristoph Flamm Bärbel Stadler, Andreas Wernitznig, Universität Wien, AT, Stefanie Widder, Ulrike Mückstein, Stefan Wuchty Ulrike öbel, Institut für Molekulare Biotechnologie, Jena, E, Walter rüner, Stefan Kopp, Jaqueline Weber