Self-Replication versus Self-Elongation

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Self-Replication versus Self-Elongation
3rd COST D27 workshop, Heraklion, Crete, Sept.
30-Oct. 3, 2004
OrHow to make long oligonucleotides without
enzymes, primers, templates, surfaces, or
stepwise feeding?
Oliver Thoennessen, Mathias Scheffler G. von
Kiedrowski, Ruhr-University Bochum
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The "standard" picture

• Who agrees?
• 1. Self-Replication
• 2. Metabolism
• 3. Mutability
• 4. Some way of keeping 1-3 connected, viz.
  compartimentation

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Chemical self-replication
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Open systems, possible non-catalyzed pathways
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Open systems possible template-directed pathways
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Dimer building blocks for an open system nYRp
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Dimer synthesis
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Ligation versus Cyclisation
C
E
D
C
n
X
Y
p

H

O
l
i
g
o
m
e
r
i
s
i
e
r
u
n
g
A
B
-
E
D
U
-
H


H
O
2

E
D
U
C
y
cl
i
s
i
-
E
D
U
CA-Cyclus
O
Reaktionsbedingungen
O
P
O
O
0.2 M EDC in 0.1 M HEPES-Puffer, 2 - 30C
O
C
/
T
1
2
-
R
i
n
g
A
/
G
n p
c( XY ) 1-10 mM Cyclisierung
B
O
H
O
n p
N
P
c( XY ) gt 20 mM
Oligomerisierung
A
O
O
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Oligomerisation of nCGp-dimers
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Reactivity of nYRp building blocks
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The current "Guiness" of prebiotic polymerisation
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No template effects in reactions using
single-sided building blocks
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Earlier results from Zielinski Orgel
Nature 1987 Experiments on a self-replicating
tetraribonucleotide analogue confirmed our
"square-root law". EDC as the source of energy,
efficient replication in GCn pGC --gt
GCnpGC J. Mol. Evolution, a few years later No
self-replication at all in a slightly different
system CGn pCG --gt CGnpCG Speculations
about the involvement of "slidomers".
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Efficient oligomerisation via sliding,
concatenation, and concatomer ligation?
free oligomers
duplexation
straight duplexes
sliding
slidomer duplexes
aggregation
concatomer
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How a concatomer might look
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Better base stacking via slidomer concatenation
CG dimer
GC dimer
CGCG slided duplex
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Thermodynamic data support slided concatomers
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Two possible modes of ligation
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SimFitting supports slidomer model
RMS 12.5
RMS 2.4
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Reaction model
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RMS as the function of a common slidomer
equilibrium factor
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"Template" addition even inhibits polymerisation
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Summary and possible significance

• The current picture to make long prebiotic
  oligomers is by primer-extension on a solid
  support (clay) via feeding with
  nucleotide-phosphorimidazolides (Ferris Orgel,
  "crepes scanario"). Traces of 50-mers can be
  detected after several weeks and daily
  replenishment of the imidazolides.
• "Self-elongation" as an alternative picture In
  the presence of the dehydration reagent EDC, the
  dimer nCGp yields high molecular weight oligomers
  (quantitatively for n gtgt 40) after 3 days.
• "Self-elongation" and "self-replication" may be
  different sides of the same coin. Exactly the
  same reason that caused poor self-replication in
  a comparable system causes efficient
  polymerisation in our system.
• Eigen, Hartman, and others have speculated that
  the earliest "genes" were rich in C and G, or
  even CG-repeats. Our experiments indicate that
  one may neither need templates nor surfaces to
  arrive at such structures.
• Outlook Co-oligomerization experiments with
  nYRp are expected to result in materials still
  rich in CG but "being doped" with other bases.
  Such materials may have the capacity to fold into
  discrete secondary structures.