From the Proliferating Microsphere to the Chemoton'

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From the Proliferating Microsphere to the
Chemoton.

• Chrisantha Fernando
• School of Computer Science
• University of Birmingham, UK
• San Sebastian, September 2006.

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The Chemoton

• Tibor Gantis hypothetical pre-enzymatic minimal
  unit of life (1971, 1973, etc..)
• Stoichometrically coupled autocatalytic
  metabolism, template and membrane systems.

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Templates control but dont encode
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The Origin of the Chemoton

• Q1. How could the notorious (L.Orgel) formose
  cycle metabolism be so nicely channeled?
• Ganti proposed the proliferating microsphere as a
  chemoton ancestor.
• A chemoton without templates, just metabolism and
  boundary.

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No template control
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Q2. Why would a proliferating microsphere become
a chemoton?

• Why would templates have interposed themselves to
  become rate-limiting in a previously well
  functioning microsphere?
• What immediate selective advantage would the
  Ganti type (i.e. non-encoding) template
  replication system confer to a proliferating
  microsphere?

?
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This is disturbing for the non-enzymatic chemoton
idea.

• Early template replication is likely to have been
  slow (low rates of p-bond formation) so the
  chemoton would be less fit than a proliferating
  microsphere!
• If Gantis claim of a non-enzymatic chemoton is
  true, he cannot call upon the ribozyme
  functionality of templates.
• The cause of evolution from PM to C is not
  explained by chemoton theory.

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Possible Explanation 1

• If PM metabolism is initially inefficient at
  producing membrane elements, R.
• If template polycondensation reactions increase
  the rate of R production.
• Then there is selection for increased initiation
  and propagation rates of polycondensation.
• This is best achieved by clean replication of
  templates with Tm chemoton operating
  temperature, rather than messy, branched polymer
  formation, i.e. chemoton selection is against all
  kinds of product inhibition.

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Possible Explanation 2

• Template Length can confer a weak Lamarkian kind
  of heredity.
• Long templates favour slow replication with high
  resting metabolite concentrations.
• Short templates favour faster replication.
• In harsh conditions, templates elongate, and this
  makes chemoton offspring have higher metabolite
  concentrations.

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Possible Explanation 3

• Short early templates conferred an advantage to
  the chemoton by having ribozyme effects.
• Ganti was wrong about the possibility of a
  chemoton without encoded catalysis.

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Q3.Do Long (non-enzymatic) templates make faster
Chemotons?

• Once a Chemoton had formed, could
  between-chemoton selection be a driving force for
  long template replication?

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Not According to Gantis Model of the Chemoton.

• According to Gantis model, long template
  replication ALWAYS results in slower chemotons,
  if template replication is rate limiting.
• This effect can be counteracted but not reversed
  by increasing initiation and propagation rates.
• But then templates loose their control
  function.

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The Unrealistic Model

• Assumes that above a monomer threshold, strands
  denature, initiate, and propagate.
• Actually, one sees dimer, trimer formation
  predominating at high monomer concentration, and
  elongation predominating at low monomer
  concentration.
• Also, there is no threshold!
• Also, sequence dependent stacking effects
  influence the capacity for replication, even in
  the absence of ribozyme effects.

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Chaos, due to leftover monomers after
division, if V is high. So What?
V 35.0
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No Chaos
Left V 5.0 Right Tsize reduced by 10x
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High Propagation Rate
Low Propagation Rate
Mean V
Template Concentration
Mean Period
Length
Length
Initialize chemotons with the same initial MASS,
i.e. for longer templates one must start with a
lower template concentration!
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A more realistic model suggests selection may
exist for short template replication

• A stochastic model of template-replication shows
  that elongation would have been a problem for
  template replication.
• Using what was learnt from this model, when
  elongation is incorporated into a chemoton model,
  there is indeed selective pressure to convert
  elongating templates to replicating templates
  with Tm near the operating temperature of the
  chemoton.

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A stochastic model helps us understand template
dynamics.

• Im not going to go into the nitty gritty of this
  stochastic model, but will present the main
  findings.
• Template elongation successfully scuppers
  template replication at low temperature.
• At high temperature, oligomer replication results
  in a skew towards very short strands.

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Eors ODE Model of Template Replication

• Considers 3 strands each double the length of the
  previous strand, in a coupled replication chain.

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conc
Low Temp
High Temp
time
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Include an Elongation Reaction
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Low Temp, High Monomer Elongation dominates
Low Temp, Low Monomer Elongation dominates
Low Temp, Low Monomer E and G decay at equal
rates. Elongation dominates
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Adding this new template model to the chemoton
model
Short Strands Predominate
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g
c
b
a
e
Note elongating template concentration decreases
because it cannot double per chemoton
replication.
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What happens to chemoton replication rate when we
increase monomer incorporation rate?
Log monomer incorporation rate
No further influence since templates are no
longer rate-limiting.
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Conclusion

• If R cannot be produced by other means, then more
  efficient template polycondensation would be
  selected for.
• However, if R is produced by other means as in
  the PM, then template polycondensation rate only
  has a slight influence on chemoton replication
  rate, by reducing back-flow into metabolism of V

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Log monomer incorporation rate
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Furthermore

• All templates can be lost from the chemoton if
  they do not double within the time of the
  chemoton.
• If stoichiometric coupling assumption is relaxed,
  then only the rapidly replicating templates can
  survive.
• Therefore in transition from PM to C, only
  templates capable of rapid replication would have
  been selected for.

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Monomer incorporation rate
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If templates do survive.

• Then the extent of the benefit to the chemoton
  depends on the tendency for metabolism to run in
  reverse without templates absorbing V.

Reverse rate 0.1
Reverse rate 0.00001
vs.
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• Short template replication could have arisen in
  the chemoton (from elongation), if template
  polycondensation could reduce back reactions of
  metabolism.

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Resource X limitation results in longer
templates.
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Conclusion

• In trying to understand why a PM would evolve
  into a C, one possibility is that messy
  polymerization reactions would have been present
  in the PM.
• PMs with greater template replication capacity
  would have been more efficient because in such
  PMs either metabolism would have been more
  irreversible, or R production would have been
  increased.

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Thanks to

• Eors Szathmary
• Guenter Von Kiedrowski
• Johan Elf and Mons Ehrenburg