Origin of life, primary pump scenario :

1
COST Action D 27
Origin of life, primary pump scenario
catalysis and concentration in this coevolutive
process. Pr Auguste Commeyras University of
Montpellier 2 -CNRS IBMM UMR-5247 Dr R. Pascal
group (DSBC)
NORDITA/Stockholm 25/29 February 2008
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The Birth of life

• Panspermia being far to be proved, life is born
  on our planet. This also means that life could
  have appeared on another one.
• Geological sciences locate the birth of life
  between 3.9 and 3.6 billion years before present
  time on our planet, which was still young (Earth
  is indeed 4.55 billion years old).
• Two converging approaches are used to study the
  extraordinary mechanism which gave birth to life
  
• The approach of the biologists who try to take
  back up the time and to go from the living beings
  towards the inert matter,
• the approach of the chemists who follow the
  direction of time and study the way used by inert
  material to become a living beings.

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The different groups of chemists working about
the origin of life can be classified within

• GENETICISTS
• METABOLISTS
• COMPARTIMENTALISTS
• COEVOLUTIONNISTS
• For coevolutionnists, all molecules and
  macromolecules essential to life were born almost
  at the same time, and under the influence of
  unique and permanent driving force.
• For coevolutionnists the emergence of
  Homochirality can be seen as a step of this
  approach. I mean a consequence of the dynamic of
  the system.
• We are coevolutionnist.

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During many years on this field we look for

• 1/ A credible INITIAL ENERGETIC SYSTEM,
• 2/ A  PERMANENT  energetic system, since it is
  probable that life could be born via trial and
  error approaches under a permanent energy
  pressure.
• 3/ Understanding the  CONSEQUENCES  of the
  permanent energy pressure by following the
  evolution of the system.
• 4/ Natural and credible processes of
   CONCENTRATION  since it seems obvious that the
  concentration of organic compounds must have been
  increased in order to favor organic reactions.
• 5/  SIMPLE WAYS , material and time savings,
  to make credible the accomplishment of the
  complex process of life emergence.

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A coevolutive scenario could be described as
follow
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Coevolutive scenario for the emergence of life.
SUN Permanent driving force
EARTH Peculiar planet on which a chemical system
maintained out of equilibrium push to the
simultaneous emergence of
Essential molecules
predisposed molecules
nucleotides triphosphates
etc
peptides
Fatty acids
RNA
which drives to the birth of genetic code, to
the compartimentalisation, and beyond, to a
"Darwinian" system
7
To have been able to go in so different
directions, the prebiotic reactions must have
been multi-directional, that means not
robust. In prebiotic chemistry the prevalent
postulate was the robustness of the reactions
and, for many years, we were not convinced by
this postulate. We became enthusiastic when we
heard about the formal contestation of the
 robustness of the prebiotic postulate  from
Albert Eschenmoser work.
8
Indeed, Albert Eschenmoser rejected this
postulate at the end of 2006, and he even
considered that the  non robust  reactions have
better potentialities than the  robust 
reactions in chemical evolution. Albert
Eschenmoser wrote

• The less robust chemical reactions in a given
  environment are, the more sensitive and
  responsive to a catalytic acceleration, and the
  higher will be their chances to become assisted
  by catalysts that may be present or be emerging
  in the environment.

Albert Eschenmoser (Conference COST D27 Barcelona
dec 2006)CHEMISTRY BIODIVERSITY Vol. 4
(2007) PP 554-573
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Emergence of different families of molecules in
the global scenario
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Coevolutive scenario for the emergence of life.
SUN Permanent driving force
EARTH Peculiar planet on which a chemical system
maintained out of equilibrium push to
simultaneous emergence of
Essential molecules
predisposed molecules
nucleotides triphosphates
etc
peptides
Fatty acids
RNA
which drives to the birth of genetic code, to
the compartimentalisation, and beyond, to a
"Darwinian" system
11
Essential molecules

• The emergence of essential molecules HCN, RCHO,
  HNCO, NO, HCCH, HCC-CN
• is well documented, see for instance the
  information given by the NASA.
• http//jpldataeval.jpl.nasa.gov/download.html
• and the 2 following NASA slides,

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http//jpldataeval.jpl.nasa.gov/download.html
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The emergence of these essential molecules is not
described further in this presentation
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Predisposed molecules
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Coevolutive scenario for the emergence of life.
SUN Permanent driving force
EARTH Peculiar planet on which a chemical system
maintained out of equilibrium push to
simultaneous emergence of
Essential molecules
predisposed molecules
nucleotides triphosphates
etc
peptides
Fatty acids
RNA
which drives to the birth of genetic code, to
the compartimentalisation, and beyond, to a
"Darwinian" system
17
Predisposed molecules

• As predisposed molecules we can list,
  aminoacides, nucleosides, nucleotides
• The discussion about the synthesis of
  a-aminoacids allows us to introduce the idea of a
  catalyst system already present in the potential
  prebiotic environnement.

18
What is now accepted is that from essential
molecules (HCN, RCHO,NH3), a-aminoacids comes
from hydrolysis of a-aminonitrile (IV). (see
below) This hydrolysis is catalysed either by
carbonyl compounds (via a-aminoalcoolate (VIII)
or carbonic anhydride (via carbamate(X)). The
rate ratio between these two pathways is at least
1000 in favor of the catalysis by carbonic
anhydride.
a-aminoacids catalysed By Carbonic anhydride
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In the primitive atmosphere the pressure of CO2
was high (between 10 and 70 bar). The pH of the
primitive ocean was about 6. So the concentration
of carbamate was high (pka of Carbamic acid being
5.8).
From the carbamate the mechanism for the
formation of hydantoïne is the following
The global catalysis of this reaction is showed
in the next slide.
  Rousset, Laspéras, Taillades, Commeyras
(1980). Tetrahedron, 36 2649-2661.
20
See the animation of the synthesis of
aminoacids and peptides in possible prebiotic
conditions.
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This work exemplifies the postulate of Albert
Eschenmoser.The synthesis of a-aminoacid (and
beyond peptides) were assisted by a catalyst (the
CO2), already present in the environment.

• The less robust chemical reactions in a given
  environment are, the more sensitive and
  responsive to a catalytic acceleration, and the
  higher will be their chances to become assisted
  by catalysts that may be present or be emerging
  in the environment.

Albert Eschenmoser (Conference COST D27 Barcelona
dec 2006)CHEMISTRY BIODIVERSITY Vol. 4
(2007) PP 554-573
23
Coevolutive scenario for the emergence of life.
SUN Permanent driving force
EARTH Peculiar planet on which a chemical system
maintained out of equilibrium push to
simultaneous emergence of
Essential molecules
predisposed molecules
nucleotides triphosphates
etc
peptides
Fatty acids
RNA
which drives to the birth of genetic code, to
the compartimentalisation, and beyond, to a
"Darwinian" system
24
With the synthesis of peptides I want to discuss
the first example of a need of concentration.
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Synthesis of peptides and the need of
concentration.

• When we have a look on the estimated
  concentration of organic molecules in the early
  ocean (0,4 mg.L-1 ltClt 400 mg.L-1 Chyba 1992 and
  Chronin 1993), it becomes obvious that the
  organic molecules were too diluted and thus
  unable to react together. So that, a process of
  concentration was necessary to allow chemical
  reactivity.
• In the primary pump scenario (next slide), our
  first idea was to use natural evaporation in
  order to increase the concentration of organic
  molecules and to make them reactive.
• Such idea of concentration by natural
  evaporation was introduced by Darwin and strongly
  supported by Stanley Miller in the drying lagoon
  scenario. Nevertheless, in drying lagoon scenario
  nothing was noticed on the mode of activation of
  molecules.

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Atmosphere
Primary Pompe
pH1,5
Beach
Ocean
Commeyras, Collet, Plasson, et al, 2002, Polymer
International. 51, 661-665.
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Synthesis of peptides and the need of
concentration.

• In the primary pump scenario the activation of
  a-amino acids is known.
• This activation through the system NO/O2 produces
  N-carboxyanhydride (NCA) and an equivalent amount
  of HNO2.
• Consequently during the formation of NCA the pH
  decreases from 6 (pH of the primitive ocean) to
  1.5.
• If the NCA stayed at this pH 1.5, it will never
  give peptides but a-aminoacids through hydrolysis
  within few hours.
• To produce peptides NCA must be poured in a water
  solution at pH 4.
• And a such rapid inversion of pH (from 1.5 to gt
  4) can not be managed in a lagoon, but only on a
  unique place on earth, that is to say on the
  beach because of the tide.
• Since primitive ocean was buffered at pH 6
  (H2CO3/HCO3Na) its beach appeared to be the
  appropriate place to run the primary pump with
  natural concentration and fast pH inversion.

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Let see the animation of this primary pump
working.
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Coevolutive scenario for the emergence of life.
SUN Permanent driving force
EARTH Peculiar planet on which a chemical system
maintained out of equilibrium push to
simultaneous emergence of
Essential molecules
predisposed molecules
nucleotides triphosphates
etc
peptides
Fatty acids
RNA
which drives to the birth of genetic code, to
the compartimentalisation, and beyond, to a
"Darwinian" system
31
To be realistic, a scenario about the emergence
of life must take into account the emergence of
precursors of RNA, RNA strands, and to have in
addition the same environment as others
prebiological materials.
Nucleotides triphosphates
32
The first information in this field was given by
Raphaël Plasson. During his PHD Raphaël Plasson
has observed a small perturbation in the curve of
hydrolysis of NCA in phosphate buffer between pH
5 and pH 7 (pH of the early ocean)
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That means that in the primary pump the NCA share
their energy.

• Jean-Philippe Biron and Robert Pascal showed
  that this perturbation in the curve of hydrolysis
  is due to the nucleophilic attack of inorganic
  phosphate on the NCA, leading to an aminoacyl
  phosphate.
• J A C S 2004, 126, 9198-9199

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The second information was given by John
Sutherland. J.S. showed that Cytidine Mono
Phosphate (CMP) is formed in only two steps in a
good yield, at 20C, neutral pH, and few hours,
from essential molecules.
We can expect that these results will be soon
extended by J.S. to the others nucleotides, AMP,
GMP, UMP.
36
The third information was obtained by our group.
Aminoacyl phosphate, in presence of AMP, gives
ATP.
ATP is characterized by emission of photons in
presence of luciferase
37
By extrapolation, all NTP (ATP, GTP,CTP, UTP)
could have been formed on the beach, in the
primary pump scenario.
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second example of concentration

• In the primary pump scenario all NTP are formed
  daily but probably with low yield.
• In water NTP are hydrolyzed.
• So their concentration cannot increase. And if
  NTP are leaved too diluted, RNA cannot be formed.
• Concentration step is required.
• Which step ? for example avoiding ATP hydrolysis
  in water.

If dATP/dt kf kh ATP , the concentration
limit of ATP in the solution depends of its
constant of hydrolysis (kh).
39
Anna Kovalova in our group recently demonstrated
that

• the stability of ATP in water is dramatically
  increased in the presence of peptides.

at 60C 30 is hydrolyzed In 3 days
3 days
4 h
1 day
At 30C or less, ATP (and probably NTP) seems
completely stable in presence of peptides. So NTP
which has been produced daily in this scenario
could have been concentrated.
40
In the primary pump scenario, the reactional
pathway to go from the atmosphere to energetic
molecules (NCA, NTP) is very short. Maximum 20
different reactions.
All these reactions are very fast geologically
speaking (few hours), they are produced in the
same conditions, in the same area and these
reactions are repeated every day. In this
scenario nature daily constructed dices (all NCA
and all NTP) and daily played with them.
Dendritic peptides are formed under kinetic and
thermodynamic control by the primary pump. They
accumulated, and progressively evolved until
homochirality.
NTP are loaded continuously in these dendritic
peptides in continuous evolution. and when good
catalytic activity appeared, RNA were formed. But
RNA were not the only sink of ATP
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Today conclusion The primary pump scenario
seems to follow the coevolutionist way

• 1/ In this global scenario the primary pump as
  INITIAL and PERMANENT ENERGETIC SYSTEM is
  proposed. This primary pump which shares its
  energy to form NTP becomes the true driving force
  of the emergent system.
• 2/ Every day, the Primary pump build starting
  dices (all NCA and all NTP), from which
  respectively peptides and RNA could be formed.
• 3/ The kinetic and thermodynamic laws, play with
  theses dices, and improve the complexity of the
  system by the technique "trial - error " due to
  the permanent energy pressure.
• 5/ A  CONSEQUENCE  of such a dynamic system,
  could be the emergence of homochirality L (by
  chance) of peptides, and homochirality D (by
  selection) of RNA.
• 6/ The ways of  CONCENTRATION  used are simple
  and natural.
• 7/ The PATHWAYS used are short, thrifty in
  material (everything is recycled) and time
  saving.
• 8/ The chemical reactions used are not robust,
  some of them are assisted by catalysts present in
  the environment, others are assisted by catalyst
  emerging in the environment.

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Thanks to Albert EschenmoserThanks to you.
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Date Sun, 24 Feb 2008 043617 0100 043617
CETDe Eschenmoser Albert ltalbert.eschenmoser_at_org
.chem.ethz.chgt  À acommeyras_at_univ-montp2.frSujet
 primary pump scenario  Dear Auguste,I
apologize for the delay of my reply to your mail
which included the documentation of your
psychologically courageous, chemically remarkable
and etiologically stimulating lecture. The delay
of my reply has to do with my recent move from
Zurich to La Jolla the first period after
arrival is always very hectic. Thank you very
much for letting me know your thoughts and
proposals as expressed in your forthcoming
lecture and, of course, please accept my special
thanks for the fairness of putting my name so
prominently on some of the slides. Naturally, I
am glad that you could so successfully make use
of the "anti-robustness postulate". Your "primary
pump scenario" impressively demonstrates the
essence of the postulate, the pragmatic part of
which is, to widen the structural landscape of
potential chemistry that chemists may include in
their origin of life research.I fully agree with
you that the marvelous ("French") catalysis of
the hydrolysis of alpha-amino nitriles by
aldehydes and CO2 are important examples of
catalytic steering of non-robust potentially
prebiotic reactions in a scenario that draws its
amino acids from HCN and aldehydes. There is no
sense in a priori questioning the etiological
relevance of a given scenario such as the one you
are pursuing what is important is that each
scenario is vigorously analyzed by its propounded
both conceptually and experimentally to the
effect that its potentials as well as its limits
become known. If all possible scenarios once will
have been subjected to such scrutiny, science
might eventually be in a much better position
with respect to its reasoning about the origin of
life. What anyway seems quite probable up grown
biology may not be the only place where symbiosis
plays an important role, some scenarios of life's
origin may well be symbiotic. If a propounder's
scenario could at the end be assigned such a
role, it would be full success.  I shall
carefully follow the experimental and conceptual
progress your scenario will make in the future,
irrespective of the fact, that at present I am
pursueing a quite different scenario (Tetrahedron
2007, vol. 63, 12821-12844). Yet, every scenario
will eventually have to deal with peptides and
nucleotides, and in this respect, yours is in
highly promising shape. With kind personal
regards and best wishes Albert