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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
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