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Darwin, Chemistry and the Origin of Life Andy Pratt Department of Chemistry OVERVIEW •Darwinian natural selection and the generation of complexity •Cells as historical artifacts •Molecular fossils •A model for the origin of life based on molecular selection •Some simple experiments involving biomimetic phosphate chemistry The complex products of natural selection http://itech.dickinson.edu/chemistry TAKING DARWIN SERIOUSLY Cells are archaeological sites The fossils are chemical: metabolites and metabolic processes Darwin, Chemistry and the Origin of Life The complex products of natural selection http://itech.dickinson.edu/chemistry The complex products of natural selection http://itech.dickinson.edu/chemistry Darwin, Chemistry and the Origin of Life Genomes & Chinese whispers: The insights of Pauling and Zuckerkandl “Jack, the next Darwin?” “Jack, the neck scar twin” “Jack, the next car wins” “Jack, the next card wins” Darwin, Chemistry and the Origin of Life TAKING DARWIN SERIOUSLY •Darwinian natural selection provides a mechanism for generating complexity •Inspiration to chemical creativity •But how did something as complex as a cell arise? •When did chemistry become biology? •The role of the selection of chemical process in the origin of life, two examples: •Catalysis and Solubility ORIGINS OF METABOLISM Features •Anaerobic environment •Rich in Iron and Sulfur •Constant input of redox energy •Carbon fixed into organic molecules •Compartments for evolution A contemporary fit •Hydrothermal vent systems •Mike Russell and others 4000 3000 Time (Mya) 2000 1000 0 http://uwnews.washington.edu/ HYDROTHERMAL VENT SYSTEMS Anaerobic carbon fixation Wood-Ljungdahl pathway - ACS / CODH Likely original anaerobic carbon fixation Biogeochemistry and element fixation Hegg, Acc. Chem. Res. 2004, 37, 775 ACS CODH Wood-Ljungdahl pathway - ACS / CODH Likely original anaerobic carbon fixation BIOMIMETIC CARBON FIXATION Carbon fixation: the reductive acetyl CoA pathway X Ni S Fe Fe CH3-B12 + CO + HSCoA CH3SH + CO S Fe S S Fe Seravalli, Kumar, & Ragsdale Biochemistry, 2002, 41, 1807 CO dehydrogenase Acetyl CoA synthase NiS, FeS, H2O,100oC Huber & Wächtershäuser, Science, 1997,276, 245 CH3COSCoA CH3COSCH3 + CH3COOH HYDROTHERMAL VENT BIOGEOCHEMISTRY? Russell & Martin, TiBS, 2004, 29, 358 BIOGEOCHEMISTRY EMERGES? O Minerals to Enzymes CO2 CO CH3X HSR N2 or NO3NH3 CO2 O CO2 H2O SR O O •BIOMIMETIC Fe(Ni)S CATALYSIS: •Huber & Wächtershäuser, Science, 1997,276, 245 •Cody et al., Science, 2000, 289, 1337 •Dörr et al, Ang. Chem. Int. Edn. Engl. 2003, 42, 1540 •Wächtershäuser etc Tet Lett., 2003, 44, 1695 IN PRINCIPLE, MIKE RUSSELL’S MOUND PROVIDES: •On going chemical input and redox gradient for energy and metabolite flux •Catalytic surfaces to mediate electron-transfer and other protobiochemical processes •Compartmentalisation in microporous material •Concentration of proto-metabolites via surface adsorption Surfaces and solutions? Evolution of chemistry of metabolism? IRON SULFIDE MICROCOMPARTMENTS Russell & Martin, Phil Trans RS (B), 2003, 358, 59 “The most important thing in life is death”- Monod FEATURES OF LIFE •Ongoing redox energy input •Occurs in discrete aqueous environments (cells) •Darwinian selection KEY EARLY DISCOVERIES OF METABOLISM • Reductive fixation of carbon generates BOTH organic molecules AND dehydrating power in water • Selective production of condensation polymers which are kinetically stable, but thermodynamically unstable PROTEINS + WATER DNA/RNA + WATER POLYSACCHARIDES + WATER AMINO ACIDS NUCLEOTIDES SUGARS “The most important thing in life is death”- Monod FEATURES OF LIFE PROTEINS + WATER DNA/RNA + WATER POLYSACCHARIDES + WATER PROTEINS + WATER DNA/RNA + WATER POLYSACCHARIDES + WATER AMINO ACIDS NUCLEOTIDES SUGARS ATP AMINO ACIDS NUCLEOTIDES SUGARS KINETIC vs THERMODYNAMIC STABILITY Molecular evolution: Molecules survive if formed faster than they degrade Kinetic stability + catalysis ATP as the harnessing of dehydrating power SURFACES: CONCENTRATION & CATALYSIS POLYPHOSPHATE ACCUMULATION O O O O P O O O O O O O P P P O OH O O O O OH Susie Meade & Ico de Zwart O2C O O P O2C O O P O O O P OH O O O O P OH O O O •Phosphate species concentrate via precipitation •Mineral catalysis of biomimetic phosphoryl transfer •Surface accumulation of polyphosphates COMPETITIVE PHOSPHATE SURFACE BINDING Glycerol-2-phosphate vs Pyrophosphate Solution phosphates separated by centrifugation Analysis by solution 31P NMR Bound phosphates solubilized with CN- COMPETITIVE PHOSPHATE SURFACE BINDING Glycerol-2-phosphate vs Pyrophosphate Organic Phosphates selectively released into solution HO HO OH OH O O O P O P O O O O HO Inorganic Phosphates selectively bound OH O O O S Fe S O P O HO P O O P O O Fe S O O Fe S Fe S Fe S Fe S Fe O O P O HO P O O S Fe S Fe S Fe S COMPETITIVE PHOSPHATE SURFACE BINDING Glycerol-2-phosphate vs Pyrophosphate Experiments repeated with other phosphate species e.g. Glycerol-2-phosphate vs Phosphate Adenosine-5’-monophosphate (AMP) vs Pyrophosphate COMPETITIVE PHOSPHATE SURFACE BINDING SELECTIVE “METABOLITE” RELEASE Glycerol-2-phosphate > Phosphate > Pyrophosphate HO OH O P O S Fe S Fe O O HO P O O O S Fe O S Fe S Fe S Fe S O O P O HO P O O Fe S Fe S Fe S Fe S •Selection for organic phosphates in solution •Homeostatic backdrop of sparingly soluble phosphates EVOLVING SOLUTION METABOLISM •Mineral surface chemistry can proliferate until the local redox gradient is dissipated •Protometabolism will ‘die’ unless it becomes mobile •Selection of solubilized autocatalytic networks which colonize new compartments •ORIGIN OF MOLECULAR EVOLUTION AND METABOLISM EVOLVING SELECTION Selection processes: •Molecules made faster than they are lost, e.g. by decomposition or dilution •Catalytic chemistry is reproduced in a new compartment before redox gradient exhausted Selection favours: •Increased autocatalytic efficiency •Manipulation of solubility equilibria •Dynamic solubility equilibria allows reproduction and homeostasis •Encapsulation of cohorts of catalytic centres EVOLVING TO AN INTEGRATED SOLUTION METABOLISM • Sparingly soluble salts • Dynamic ion exchange Homeostasis Control of solubility via: • Redox • Organic ligands for phosphate (e.g. organic derivatives) and Fe2+ (peptides) Competitive equilibria (e.g. S2-) Pi • Feedback loops Pi • Micellar encapsulation Pi Pi Pi Pi Fe2+ Fe3+ Fe2+ Fe2+ Fe3+ S2- S2- S2- S2- S2- S2- Fe2+ Pi Fe2+ Fe2+ Fe2+ Fe2+ S2- S2- S2- S2- Many thanks to Ico de Zwart Susie Meade Marie Squire Ward Robinson Mike Russell (NASA) and Evolving catalysis by the mineral surface FeS is deposited as Mackinawite Figure: Russell & Hall, GSA Memoir 198 (2006), 1 Mackinawite, Greigite and the Origin of Molecular evolution? Electrontransfer co-factor Fig: Rickard & Luther, Chemical Reviews, 2007, 107, 514-62 Mackinawite & Greigite Fig: Rickard & Luther, Chemical Reviews, 2007, 107, 514-62 Greigite FeII/III FeII Fig: Rickard & Luther, Chemical Reviews, 2007, 107, 514-62 Mackinawite, Greigite and the Origin of Molecular evolution? Fe2+(aq) S2-(aq) Mackinawite (FeS) CO2 CH3COSR Greigite (Fe3S4) Pi Pyruvate Organic ligands Amino acids Peptides AcPi Pi PPi THE INVENTION OF METABOLISM CO2 Organics + Fe3+ Fe2+ • CO2: weak electron acceptor • FeS: electron donor S2- • • • • Electron transfer slow without catalysis Iron sulfides provide generic catalysis Ligands & Fe3+ provide feedback loop Reproduction with variation and selection Protein FeS Clusters Rao & Holm Chem. Rev. 2004, 104, 527 “Nothing in Biology Makes Sense Except in the Light of Evolution” Theodore Dobhzhansky Complexity of Life: a product of •Reproduction •Variation •Selection •Life is a process not an entity •Cells are historical documents CHEMICAL FUNDAMENTALS OF LIFE Energy • • • • • Thermochemical gradient Kinetic barrier to dissipation CATALYSIS Feedback loops AUTOCATALYSIS SELECTION for enhanced catalysis • EVOLUTION of autocatalytic loops • REPLICATION of autocatalysis with VARIATION and SELECTION LIFE is a PROCESS, not an ENTITY Based on REPLICATION of METABOLIC INFORMATION with VARIATION & SELECTION Energy CHEMICAL FUNDAMENTALS OF LIFE • METABOLIC EVOLUTION The greatest improvement in the productive powers of labour, and the greater part of the skill, dexterity, and judgment with which it is any where directed, or applied, seem to have been the effects of the division of labour. An Inquiry into the Nature and Causes of the Wealth of Nations, Adam Smith CHEMICAL FUNDAMENTALS OF LIFE Energy • METABOLIC EVOLUTION •At start: inefficient GENERIC catalysts •REPLICATION with VARIATION and SELECTION diversified, more effective catalysts •Need LOCALIZATION (compartments) Ongoing & later issues: •Evolving COMPLEXITY of interlocked autocatalytic cycles •Benefit of REPLICATION FIDELITY •HOMEOSTASIS Greigite mimics diverse Fe4S4 clusters Feedback loop: C-fixation induces mineral change; creates better catalyst; increases C-fixation rate