darwin, chemistry and the origin of life andy pratt department of chemistry andy pratt department of...
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Darwin, Chemistry
and the Origin of
Life
Darwin, Chemistry
and the Origin of
LifeAndy Pratt
Department of Chemistry
Andy PrattDepartment of Chemistry
•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
OVERVIEW
http://itech.dickinson.edu/chemistry
The complex products of
natural selection
The complex products of
natural selection
Darwin, Chemistry and the Origin of Life
Darwin, Chemistry and the Origin of Life
TAKING DARWIN SERIOUSLY
Cells are archaeological sitesThe fossils are chemical: metabolites and metabolic processes
http://itech.dickinson.edu/chemistry
The complex products of
natural selection
The complex products of
natural selection
http://itech.dickinson.edu/chemistry
The complex products of
natural selection
The complex products of
natural selection
Darwin, Chemistry and the Origin of Life
Darwin, Chemistry and the Origin of Life
Genomes & Chinese whispers:The insights of Pauling and Zuckerkandl
Genomes & Chinese whispers:The insights of Pauling and Zuckerkandl
“Jack, the next card wins”
“Jack, the next car wins”
“Jack, the neck scar twin”
“Jack, the next Darwin?”
Darwin, Chemistry and the Origin of Life
Darwin, Chemistry and the Origin of Life
•Darwinian natural selection provides a mechanism for generating complexity•Inspiration to chemical creativity
TAKING DARWIN SERIOUSLY
•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
Time (Mya) 010004000 20003000
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
HYDROTHERMAL VENT SYSTEMS
http
://u
wne
ws.
was
hing
ton.
edu/
Anaerobic carbon fixation
Wood-Ljungdahl pathway - ACS / CODHLikely original anaerobic carbon fixation
Wood-Ljungdahl pathway - ACS / CODHLikely original anaerobic carbon fixation
Hegg, Acc. Chem. Res. 2004, 37, 775
ACS CODH
Biogeochemistry and element fixation
BIOMIMETIC CARBON FIXATIONCarbon fixation: the reductive acetyl CoA pathway
CH3-B12
+ CO + HSCoA
CH3COSCoACO dehydrogenaseAcetyl CoA synthase
CH3SH+ CO
CH3COSCH3 +CH3COOHNiS, FeS,
H2O,100oCHuber & Wächtershäuser, Science, 1997,276, 245
Seravalli, Kumar, & Ragsdale Biochemistry, 2002, 41, 1807
S
Fe S
Fe
Fe
SX
Fe
S
Ni
HYDROTHERMAL VENT BIOGEOCHEMISTRY?
Russell & Martin, TiBS, 2004, 29, 358
BIOGEOCHEMISTRY EMERGES?
•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
O
O
CO2
O
O
SR
CO2 COCH3X
HSR
CO2
NH3
H2O
N2 or NO3-
Minerals to
Enzymes
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 MICROCOMPARTMENTSRussell & Martin, Phil Trans RS (B), 2003, 358, 59
“The most important thing in life is death”- MonodFEATURES 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 + WATERDNA/RNA + WATERPOLYSACCHARIDES + WATER
AMINO ACIDSNUCLEOTIDESSUGARS
“The most important thing in life is death”- MonodFEATURES OF LIFE
PROTEINS + WATERDNA/RNA + WATERPOLYSACCHARIDES + WATER
AMINO ACIDSNUCLEOTIDESSUGARS
ATP
KINETIC vs THERMODYNAMIC STABILITYMolecular evolution: Molecules survive if formed faster than they degradeKinetic stability + catalysisATP as the harnessing of dehydrating power
PROTEINS + WATERDNA/RNA + WATERPOLYSACCHARIDES + WATER
AMINO ACIDSNUCLEOTIDESSUGARS
SURFACES: CONCENTRATION & CATALYSIS POLYPHOSPHATE ACCUMULATION
Susie Meade & Ico de Zwart
•Phosphate species concentrate via precipitation•Mineral catalysis of biomimetic phosphoryl transfer•Surface accumulation of polyphosphates
O
OP
O
O
OO
P
O
OP
OH
O
OOO
POH
O
O
O
O
O2C OP
O
O
OO
P
O
OP
OH
O
OOO
POH
O
O
O2C O
COMPETITIVE PHOSPHATE SURFACE BINDING
Bound phosphates solubilized with CN-
Solution phosphates separated by centrifugation
Analysis by solution 31P NMR
Glycerol-2-phosphate vs Pyrophosphate
Glycerol-2-phosphate vs Pyrophosphate
OH
SFe
SFe
SFe
SFe
SFe
SFe
SFe
SFe
OP
O
O
O
OH
OP
O
O
O
SFe
SFe
S
P
O
O
HO O P
O
O
OP
O
O
HO O P
O
O
O
OH
OP
O
O
O Inorganic Phosphates selectively bound
Organic Phosphates selectively released into
solution
HOHO
HO
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
SFe
SFe
SFe
SFe
SFe
SFe
SFe
SFe
SFe
SFe
S
P
O
O
HO O P
O
O
OHO P
O
O
O
OH
OP
O
O
O
Glycerol-2-phosphate > Phosphate > Pyrophosphate
HO
•Selection for organic phosphates in solution•Homeostatic backdrop of sparingly soluble phosphates
COMPETITIVE PHOSPHATE SURFACE BINDING
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 SELECTIONSelection 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
Pi
Fe2+ Fe3+ Fe2+ Fe2+
Pi Pi
Fe3+
Pi
EVOLVING TO AN INTEGRATED SOLUTION METABOLISM
• Sparingly soluble salts• Dynamic ion exchange HomeostasisControl of solubility via:• Redox• Organic ligands for phosphate (e.g. organic
derivatives) and Fe2+ (peptides)Competitive equilibria (e.g. S2-)• Feedback loops• Micellar encapsulation
S2- S2- S2- S2-
Pi
Fe2+
S2-
Fe2+ Fe2+ Fe2+ Fe2+
Pi
PiS2-
S2- S2- S2- S2-
Many thanks to
Ico de ZwartSusie MeadeMarie Squire
Ward RobinsonMike 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?
Fig: Rickard & Luther, Chemical Reviews, 2007, 107, 514-62
Electron-transfer co-factor
Mackinawite & Greigite
Fig: Rickard & Luther, Chemical Reviews, 2007, 107, 514-62
Greigite
Fig: Rickard & Luther, Chemical Reviews, 2007, 107, 514-62
FeII/III
FeII
Mackinawite, Greigite and the Origin of Molecular evolution?
Fe2+(aq) S2-(aq)
Mackinawite (FeS)
Pyruvate
Amino acids
Peptides
Organic ligands
Greigite (Fe3S4)
CO2
CH3COSR AcPi
PPi
Pi
Pi
THE INVENTION OF METABOLISM
• Electron transfer slow without catalysis
Fe2+
S2-
CO2
Organics+ Fe3+
• Iron sulfides provide generic catalysis• Ligands & Fe3+ provide feedback loop• Reproduction with variation and selection
• CO2: weak electron acceptor• FeS: electron donor
Protein FeS ClustersRao & Holm Chem. Rev.
2004, 104, 527
Complexity of Life: a product of
•Reproduction
•Variation
•Selection
“Nothing in Biology Makes Sense Except in the Light of Evolution”
Theodore Dobhzhansky
•Life is a process not an entity•Cells are historical documents
CHEMICAL FUNDAMENTALS OF LIFE• Thermochemical gradient• Kinetic barrier to dissipation• CATALYSIS
Ene
rgy
• Feedback loops AUTOCATALYSIS• SELECTION for enhanced catalysis
• EVOLUTION of autocatalytic loops• REPLICATION of autocatalysis with
VARIATION and SELECTION
LIFE is a PROCESS, not an ENTITYBased on REPLICATION of METABOLIC INFORMATIONwith VARIATION & SELECTION
CHEMICAL FUNDAMENTALS OF LIFEE
nerg
y
• 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 LIFEE
nerg
y
• 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