Transcript A Model of Chemical Evolution

How Natural Selection could
Evolve Metabolism.
Chrisantha Fernando
School of Computer Science
University of Birmingham, UK
San Sebastian, September 2006
The Problem Defined:
 The multiple source hypothesis proposes
that a great variety of organic synthesis
routes could have produced organic
molecular variety.
 Eg…..
 A.I. Oparin & J.B.S. Haldane (1924,1929). UV light
energy, Fox and Dose, Folsome, etc.. Amino acid polym.
 G. Wachtershauser. FeS/H2S reducing power produces
COO-, -S-, -COS-, neg charged metabolism on surface.
 S. Miller. Electrical discharges make Aas, aldehydes, etc..
in reducing conditions
 C. de Duve. Thioester metabolism on surfaces.
 H. Morowitz. Reverse Citric acid cycle on mineral
surfaces, (autocatalytic step so far a problem).
 Decker, Ganti. Formose cycle feeding on Formaldehyde
and other aldehydes formed from perhaps a Miller like
reaction or CO and H2O + light at pressure (Hazen et al).
 Chyba and Astrobiology. Organics from space, meteoric
origin of organics.
 Tommy Gold. Abiotic synthesis of hydrocarbons!
(Controversial).
Ingredients but no Recipe?
 Given a wide range of ingredients to choose from,
what process resulted in the origin of metabolism?
 We seek
 I. The minimal autopoetic chemical organization
capable of the “recursive generation of functional
constraints”, initially in the absence of template
replication.
 II. The properties of the ingredients, and the recipe,
required to produce a metabolism, ultimately capable of
evolving template replication.
Selection and Drift in Phase
Separated Spots
 Operin suggested natural selection between
coacervates and Dyson modeled the effect of drift
in such systems and the probability of transition
from simpler to more ‘complex’ metabolisms.
 Thought experiments and models of natural
selection between coacervate-like entities.
 Replication rate is correlated with steady-state
light absorption due to: direct growth
enhancement and an energy constraint on
information transmission.
 Novelties arise through chemical ‘avalanches’.
Assumptions
 Assumption 1: Phase separated spots form
on a liquid surface. They proliferate due to
supply of oily ‘food’ material that perhaps
falls in rain. They divide by agitation and
are subject to random loss, with geological
recycling of their ‘food’ back to the
atmosphere.
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The First Autotrophic Unit
is at the Level of a
Geophysical Cycle
Chemical recycling
Physical recycling
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abb + abb + light ----> ba + abbb
 Assumption 2: Within the oil phase, there exists a
potential light absorbing reaction that can re-form
abbb and a high energy molecule ba. But to start
with there is no abb so this reaction cannot
actually take place.
 Assumption 2.1. In addition, light absorbing
products may be much longer, and contribute
more to spot growth than non-driven reactions.
Long molecules stay in spots better than short
ones.
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or longer molecule
1. A light absorbing reaction may produce molecules that make
the spot grow faster directly.
 Assumption 3: Spots able to absorb abbb
more quickly obviously proliferate faster.
 If a spot contains high energy species that
react with abbb molecules in chemical
reactions that produce spot localized
contents, then abbb absorption rate can be
increased greatly (irreversibility of this
reaction is ++ favoured).
2. High energy reactants can shift the equilibrium of ‘food’
promoting growth.
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 Assumption 4: Novel species are produced by rare
bimolecular rearrangement reactions between
existing species, e.g. abbb and other food species,
e.g.
 abbb + abbb -(v. low flux ~ 0)-> ba + bbbbba
 Both ba and bbbbba are novel species, present at
initially very low concentration e.g. 0.0000001M,
in actual fact, much less than this, i.e. 1 molecule!
 Assumption 5: Once a novel species is produced,
it may react in spontaneous high flux reactions
with a proportion of other species,e.g. 0.01%, 1%,
5% etc…
 However, by definition such novel reactions must
have insignificant reverse rates if their product is
any existing species, otherwise, reverse flux
through this reaction would have been observed
before the novel rare species arose, and the novel
species would therefore not have been novel!
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 Assumption 6: For each novel species
produced in high flux reactions, the high
flux reactions it takes part in are again
calculated, resulting in a potential
‘avalanche’ of novel reactions. Avalanche
size distribution will depend on the
proportion P each species reacts with.
Determining the Avalanche.
1.
2.
aaa + b
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3.
bbbbbaa + a
Energy for Information
3. Energy required to replicate babb, (high k2).
4. Energy required for babb to have influence (high k3).
 Assumption 7 : Division occurs due to absorption
of abbb at regular intervals.
 Replication rate is increased if abbb undergoes
chemical reactions with the material in the spot to
produce spot phase material, (longer polymers
being more likely to be spot-phase). Division
occurs when the volume reaches some noisy
threshold.
 One definition of fitness is time to reach this
threshold. In the simulation, fitness could be
defined as the total mass of material absorbed into
the spot in fixed time T.
Low energy vs. high energy
spots.
 Spots growing by incorporation of low energy
material are disadvantaged because,
 Absorption of abbb by chemical reactions is
thermodynamically unfavorable.
 Unable to create the thermodynamically unfavorable
longer polymers that greatly benefit spot growth.
 Unable to sustain autocatalysis required for the
‘channeling’ of the reaction network.
 High energy autocatalytic particles can more effectively
channel the reaction network than low energy
autocatalytic particles.
Selection at the Level of the
Geophysical Unit?
 Low energy spot material requires more energy for
recycling back to abbb by the autotrophic
geophysical metabolism.
 If [abbb] in rain is limited by recycling rate, then
geophysical units with greater abbb production
mediate greater energy flux, more replication, and
hence more natural selection.
 A spot that produces abbb not only benefits itself,
but benefits all other spots in the geophysical unit.
Preliminary Models.
 In the models so far I did not have this
elaborate geophysical unit conception, but
attempted to directly select for increased
steady-state light absorption in spots.
 The artificial selection experiment is
intended to capture some of the dynamics
just presented.
Aim of the Models
 I use a 1:1 GA to artificially seelct ‘spots’
satisfying a fitness function.
 What chemical organizations are produced,
e.g. autocatalytic cycles etc..?
 What is the ratio of harmful reactions to
beneficial reactions as a function of the
properties of chemical variation, the food
set and the fitness function?
Main Findings
 Experiments selecting for high steady-state light
absorption show adaptive avalanches v. rare
because.
 Probability of growth of novel low concentration
product is small.
 Probability that novel product has beneficial spot-level
effect is small.
 Bimolecular rearrangement reactions tend to produce
divergent networks (not closed), not such a problem if
autocatalytic growth of novel product is occurring.
 Increasing food set size increases probability of
adaptations.
 Early experiments selecting for abbb uptake rate:
Light absorption reaction not always utilized.
 Adaptive frequency decreases over evolution?
The Chemistry
 Bimolecular rearrangement reactions of binary atoms, e.g.
 abbb + ba <----> abb + abb
 Each molecule has free energy of formation, G.
 Two types of reaction.
 Irreversible (and reversible) exogonic reactions (heat producing)
 Irreversible endogonic reaction (light absorbing)
 When generating novel reactions ensure they are always
spontaneous.
kf = 0.01*e-dG/RT
kb = 0.01,
dG = (Gproducts - Greactants)
The Initial Network
R = gas constant, T = 300K
Artificial Selection
Control Experiment
 Information (i.e. modification of reaction
structure) implicit. Now reactions can just
be formed and removed randomly! No need
for the evolution of “engram autocatalysis”.
 Autocatalytic reaction network evolved.
 High energy hub molecules drive reactions,
e.g. babb.
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 Fitness is largely unaffected if the network is initialized
with 100mM abbb plus any one of the following species at
0.1mM; ba, ab, abb, babb, babbb, bbbbbba.
 However, if the network is initialized with 100mM abbb
alone, or with 100mM abbb + 0.1mM bbab, bbabab,
bbbba, bab, bbabb, or bbbaabab, etc… then fitness = 0.
 I.e. the network reacts abbb (food) with inherited high
energy molecules (self) to produce abb.
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Full Experiment
 Avalanche type variation introduced.
 No adaptations evolved with just abbb as food,
within 80,000 generations, and after several runs!
To solve this problem….
 More food molecule types introduced.
 ab,aab, aaab, aabb, abbb, aaaab, aaabb, aabbb, abbbb
 Only one initial reaction defined at outset.
 abb + abb ---> ba + abbb
 Therefore initial fitness = 0.
 More possible small molecule reactions undefined.
Fitness
Fitness
3Sept_10_0_05
Generation
Conc
3Sept_10_0_05
abbb,aaab,aabb,
(aaaab)* Not used.
aab
abbb
ba
abb
Time
3Sept_10_0_05
- High energy food used
to drive new reactions.
-ba from light not used?
1kJ
1kJ
1
1kJ
5kJ
0.27kJ
91
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1kJ
0.4kJ
1.68
0.68kJ
13
0.15kJ
1kJ
Rare novel molecule
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Fitness
1.
2.
3.
4.
5Sept1
Preference for same
length species to react.
Probability of a particle
being catalytic is related
to the proportion of p.
Prob reaction
proportional to 1/L2.
Initial [rare species] =
0.00001
5Sept2
No preference for particles
of the same length to react.
5Sept3
1/L not 1/L2
5Sept4
No b related catalysis probability effect.
Generation
5Sept5. No length dependence
5Sept6
Initial [rare] = 0.0000001
Not 0.00001
The Evolutionary History of Experiment 5Sept1
2329
2427
2200
75.852
2200,2201,2205
2201
20.6873
2205
1
66 2
66 2
12 1
91.9089
23.8513
2329
1.07852
2427
5Sept1
The Evolutionary History of Experiment 5Sept2
296.704
[abb]
5.27797
221.193
[abb]
[abb]
Properties of Evolved Networks
 Many different food molecules are typically
utilized, e.g. aabb, abbb, aaab, abbb.
 Novel products (X) often catalyse a reaction with
a food molecule, e.g.
 X + abbb ---> X + babb
The novel product typically then reacts with another food
molecule to re-form the X, e.g.
babb + aaab ----> X + Waste
See next diagram…
Engram Autocatalysis was evolved.
X
F1
X
a
F2
W
This is two step autocatalysis,
i. Step one, catalysis.
ii. Step two, formation of another catalyst.
The complex networks exhibit many such two step
autocatalysis reactions.
Conclusions
 Often the child networks (even without mutation)
are less fit that the parent network, due to a nonheritable adaptation in the parent.
 Sometimes there are children of greater fitness
than parents produced in quick succession, as
[abb] increases over several generations due to the
same adaptation in the parent. This can mask
harmful reactions in the offspring.
 The use of the 1:1 GA is restrictive, not allowing
selection for robustness to variation, as would be
expected with a larger population size, and a high
probability of variation.
 Ecological dynamics between spots having
different metabolic roles are not considered.
 Novel reactions are sustained by the evolution of
autocatalytic species, “engram autocatalysts”.
 The light absorbing molecule itself shows
autocatalytic growth, since this maximizes fitness
of the spot, “growth autocatalysis”.
 No micro-mutation is necessary if sufficient
variety of random catalytic avalanches exists, and
if harmful avalanches can be prevented spreading.
Fitness = Maximization of
polymer mass ~ Spot Growth
Rate
 Fitness = Sum over all i species of
 Speciesi Length x [Speciesi] at end of trial.
 Excluding all food molecules.
 Initial conditions as before,I.e. all food [molecule]
= 100mM, except [abbb] = 0mM
 Will the light absorbing reaction of abb be utilized
to produce high energy species, as a side-effect of
selection for growth rate?
Fit
No further adaptation in
the whole trial!?!?!?
5Mass1
No further adaptation in
the whole trial!?!?!?
5Mass2
Gen
Gen
No further adaptation in
the whole trial!?!?!?
5Mass3
Gen
5Mass4
Gen
Why are avalanches
So unlikely to be adaptive?
5Mass5
5Mass6
The Evolutionary History of Experiment 5Mass1
831.259
593
Light absorbing reaction lost.
528
The Evolutionary History of Experiment 5Mass2
abb not produced.
139
The Evolutionary History of Experiment 5Mass3
abb produced.
323
The Evolutionary History of Experiment 5Mass4
abb produced but light
absorbing reaction lost
The Evolutionary History of Experiment 5Mass6
abb produced.
Conclusion
 In some runs abb is produced, but some reactions
loose the light absorbing reaction.
 Further analysis is required to know how much
heat dissipation is based on energy obtained from
food molecules vs. from light.
 Why are there such long periods without an
adaptive avalanche, when networks are larger?
Thanks to…





Kepa Ruiz-Mirazo
Jon Rowe
Eors Szathmary
Graham Cairns-Smith
Guenter Wachtershauser