> coded instruction sets
> are components of Nature.
just some clips;
==
Many important biomolecules are thermally unstable in aqueous media;
for instance, functionalized sugars (both aminated and phosphorylated),
peptides, polyphosphates, or thioesters will not survive long in water
under hot hydrothermal conditions (e.g., Larralde et al. 1995; Shapiro
1995). Nitriles, such as cyanoacetylene and cyanoacetaldeyde � proposed
as possible prebiotic precursors for pyrimidines (Robertson & Miller
1995)
� will be rapidly hydrolyzed to carboxylic acids in hot water (Siskin et
al. 1990). Therefore, if the synthesis of nucleotides and their
subsequent
oligomerization to promote an "RNA" world is requisite to the emergence
of life, then such chemistry would be extremely improbable
(and likely impossible) in high-temperature water
(e.g., Miller & Lazcano 1995).
===
===
The discovery of hydrothermal vents at the oceanic ridge crests and
the appreciation of their significance in the element balance of the
hydrosphere represents a major development in oceanography [126].
Since the process of hydrothermal circulation probably began early in
the Earth�s history, it is likely that vents were present in the Archean
oceans. Large amounts of ocean water now pass through the vents,
with the whole ocean going through them every 10 million years [127].
This flow was probably greater during the early history of the Earth,
since the heat flow from the planet�s interior was greater during
that period. The topic has received a great deal of attention, partly
because of doubts regarding the oxidization state of the early
atmosphere. Following the first report of the vents� existence,
a detailed hypothesis suggesting a hydrothermal emergence of life
was published [128], in which it was suggested that amino acids and
other organic compounds are produced during passage through the
temperature gradient of the 350 �C vent waters to the 0 �C ocean waters.
Polymerization of the organic compounds thus formed, followed by their
self-organization, was also proposed to take place in this environment,
leading to the first forms of life.
At first glance, submarine hydrothermal springs would appear
to be ideally suited for creating life, given the geological
plausibility of a hot early Earth. More than a hundred vents
are known to exist along the active tectonic areas of the Earth,
and at least in some of them catalytic clays and minerals interact
with an aqueous reducing environment rich in H2, H2S, CO, CO2,
and perhaps HCN, CH4, and NH3.
Unfortunately it is difficult to corroborate these speculations with
the findings of the effluents of modern vents, as a great deal of the
organic material released from modern sources is diagenized biological
material, and it is difficult to separate the biotic from the abiotic
components of these reactions. Much of the organic component of
hydrothermal
fluids may be formed from diagenetically altered microbial matter.
So far, the most articulate autotrophic hypothesis stems from
the work of W�chtersh�user [129,130], who has argued that life
begun with the appearance of an autocatalytic, two-dimensional
chemolithtrophic metabolic system based on the formation of the
highly insoluble mineral pyrite (FeS2).
The reaction FeS + H2S -> FeS2+ H2 is very favorable.
It is irreversible and highly exergonic with a standard
free energy change ?G� = -9.23 kcal/mol, which corresponds
to a reduction potential E� = -620 mV. Thus, the FeS/H2S
combination is a strong reducing agent, and has been shown
to provide an efficient source of electrons for the reduction
of organic compounds under mild conditions. The scenario proposed
by W�chtersh�user [129,130] fits well with the environmental
conditions found at deep-sea hydrothermal vents, where H2S, CO2,
and CO are quite abundant. The FeS/H2S system does not reduce CO2
to amino acids, purines, or pyrimidines, although there is more
than adequate free energy to do so [131]. However, pyrite formation
can produce molecular hydrogen, and reduce nitrate to ammonia,
and acetylene to ethylene [132]. More recent experiments have shown
that the activation of amino acids with carbon monoxide and (Ni,Fe)S
can lead to peptide-bond formation [133]. In these experiments,
however, the reactions take place in an aqueous environment to which
powdered pyrite has been added; they do not form a dense monolayer
of ionically bound molecules or take place on the surface of pyrite.
None of the experiments using the FeS/H2S system reported so far
suggests that enzymes and nucleic acids are the evolutionary outcome
of surface-bounded metabolism. The results are also compatible with
a more general model of the primitive soup in which pyrite formation
is an important source of electrons for the reduction of organic com-
pounds. It is possible that under certain geological conditions the
FeS/H2S combination could have reduced not only CO but also CO2
released from molten magna in deep-sea vents, leading to biochemical
monomers [134]. Peptide synthesis could have taken place in an iron
and nickel sulfide system [133] involving amino acids formed by elec-
tric discharges via a Strecker-type synthesis,
although this scenario requires the transportation of compounds formed
at the surface to the deep-sea vents [135]. It seems likely that
concentrations of reactants would be prohibitively low
based on second-order reaction kinetics.
If the compounds synthesized by this process did not remain bound
to the pyrite surface, but drifted away into the surrounding aqueous
environment, then they would become part of the prebiotic soup, not
of a two-dimensional organism.
=================================
In general, organic compounds are decomposed rather than created
at hydrothermal vent temperatures, although of course temperature
gradients exist. As has been shown by Sowerby and coworkers [136],
concentration on mineral surfaces would tend to concentrate any
organics created at hydrothermal vents in cooler zones, where other
reaction schemes would need to be appealed to.
=================================
The presence of reduced metals and the high temperatures of
hydrothermal vents have also led to suggestions that reactions
similar to those in Fischer�Trospch-type (FTT) syntheses may be
common under such regimes. It is unclear to what extent this is
valid, as typical FTT catalysts are easily poisoned by water and
sulfide. It has been argued that some of the likely environmental
catalysts such as magnetite may be immune to such poisoning [137].
Stability of Biomolecules at High Temperatures
A thermophilic origin of life is not a new idea. It was first suggested
by Harvey [138], who argued that the first life forms were het-
erotrophic thermophiles that had originated in hot springs such as
those found in Yellowstone Park. As underlined by Harvey, the one
advantage of high temperatures is that the chemical reactions could
go faster and the primitive enzymes could have been less efficient.
However, high temperatures are destructive to organic compounds.
Hence, the price paid is loss of biochemical compounds to decomposition.
Although some progress has been made in synthesizing small
molecules under hydrothermal vent type conditions, the larger trend
for biomolecules at high-temperature conditions is decomposition. As
has been demonstrated by various authors, most biological molecules
have half-lives to hydrolysis on the order of minutes to seconds at
the high temperatures associated with hydrothermal vents. As noted
above, ribose and other sugars are very thermolabile compounds [79].
The stability of ribose and other sugars is problematic, but pyrimidines
and purines, and many amino acids, are nearly as labile. At 100 �C
the half-life for deamination of cytosine is 21 days, and 204 days for
adenine [139,140]. Some amino acids are stable, for example, alanine
with a half-life for decarboxylation of approximately 19,000 years
at 100 �C, but serine decarboxylates to ethanolamine with a half-life of
320 days [141]. White [142] measured the decomposition of various com-
pounds at 250 �C and pH 7 and found half-lives of amino acids from 7.5 s
to 278 min, half-lives for peptide bonds from <1min to 11.8 min,
half-lives for glycoside cleavage in nucleosides from <1s to 1.3 min,
decomposition of nucleobases from 15 to 57min, and half-lives for
phosphate esters from 2.3 to 420 min. It should be borne in mind
that the half-lives for polymers would be even shorter as there
are so many potential breakage points in a polymer. Thus, while
the vents may serve as synthesis sites for simpler compounds such
as acetate or more refractory organic compounds such as fatty acids,
it is unlikely they played a major role in synthesizing most
biochemicals or their polymers.
350�C submarine vents do not seem to presently synthesize organic
compounds, more likely they decompose them in a time span ranging
from seconds to a few hours. Thus, the origin of life in the vents is
improbable. This does not imply that the hydrothermal springs were a
negligible factor on the primitive Earth. If the mineral assemblages
were sufficiently reducing, the rocks near the vents may have been
a source of atmospheric CH4 or H2. As stated earlier, the concentra-
tions of biomolecules which could have accumulated on the primitive
Earth is governed largely by the rates of production and the rates
of destruction. Submarine hydrothermal vents would have also been
important in the destruction rather than in the synthesis of organic
compounds, thus fixing the upper limit for the organic compound
concentration in the primitive oceans. Although it is presently not
possible to state which compounds were essential for the origin of life,
it does seem possible to preclude certain environments if even fairly
simple organic compounds were involved [143].
79. Larralde, R., M. Robertson and S. Miller.
Rates of decomposition of ribose and other sugars:
implications for chemical evolution. Proceedings of
the National Academy of Sciences USA, 92:8158�60, 1995.
126. Corliss, J., J. Dymond, L. Gordon, J. Edmond,
R. von Herzen, R. Ballard, K. Green, D. Williams,
A. Bainbridge, K. Crane and T. van Andel. Submarine
thermal springs on the Galapagos Rift. Science, 203:1073�83, 1979.
127. Edmond, J., K. Von Damn, R. McDuff and C. Measures. Chemistry of
hot springs on the east Pacific Rise and their effluent dispersal.
Nature, 297:187�91, 1982.
128. Corliss, J., J. Baross and S. Hoffman.
An hypothesis concerning the relationship between
submarine hot springs and the origin of life on Earth.
Oceanologica Acta, 4 Suppl, 59�69, 1981.
129. W�chtersh�user, G. Before enzymes and templates:
theory of surface metabolism. Microbiological Reviews,
52:452�84, 1988.
130. W�chtersh�user, G. Groundworks for an
evolutionary biochemistry: the iron-sulphur world.
Progress in Biophysical Molecular Biology
58:85�201,1992.
131. Keefe, A., S. Miller, G. McDonald and J. Bada.
Investigation of the prebiotic synthesis of amino acids
and RNA bases from CO2 using FeS/H2S as a reducing agent.
Proceedings of the National Academy of Sciences USA,
92:11904�6, 1995.
132. Maden, B. No soup for starters? Autotrophy and
origins of metabolism. Trends in Biochemical Sciences,
20:337�41, 1995.
133. Huber, C. and G. W�chtersh�user. Peptides by
activation of amino acids with CO on (Ni, Fe)S surfaces
and implications for the origin of life.
Science, 281:670�2, 1998.
134. Orgel, L. The origin of life�a review of facts
and speculations. Trends in Biochemical Sciences,
23:491�5, 1998.
135. Rode, B. Peptides and the origin of life.
Peptides, 20:773�86, 1999.
136. Sowerby, S., C. Morth and N. Holm. Effect
of temperature on the adsorption of adenine.
Astrobiology, 1(4):481�7, 2001.
137. Holm, N. and E. Andersson. Hydrothermal systems.
In Brack, A. (Ed.), The Molecular Origins of Life:
Assembling the Pieces of the Puzzle (pp.86�99).
Cambridge University Press, Cambridge, 1998.
138. Harvey, R. Enzymes of thermal algae. Science, 60:481�2, 1924.
139. Garrett, E. and J. Tsau. Solvolyses of cytosine and cytidine.
Journal of Pharmaceutical Sciences, 61(7):1052�61, 1972.
140. Shapiro, R. The prebiotic role of adenine:
a critical analysis. Origins of Life and Evolution
of the Biosphere, 25:83�98, 1995.
141. Vallentyne, J. Biogeochemistry of organic matter.
II. Thermal reaction kinetics and transformation products
of amino compounds. Geochimica et Cosmochimica Acta, 28:157�88, 1964.
142. White, R. Hydrolytic stability of biomolecules
at high temperatures and its implication for life at 250�
C. Nature, 310(5976):430�2, 1984.
143. Cleaves, H. and J. Chalmers. Extremophiles may
be irrelevant to the origin of life. Astrobiology, 4(1):1�9, 2004.
144. Or�, J. Comets and the formation of biochemical
compounds on the primitive Earth. Nature, 190:442�3, 1961.
"Unless the molecule can literally copy itself,"
Joyce and Orgel note, "that is, act simultaneously
as both template and catalyst, it must encounter
another copy of itself that it can use as a template."
Copying any given RNA in its vicinity will lead to
an error catastrophe, as the population of RNAs
will decay into a collection of random sequences.
But to find another copy of itself, the self-replicating
RNA would need (Joyce and Orgel calculate)
a library of RNA that "far exceeds
the mass of the earth."
Joyce G.F. & Orgel L.E., "Prospects for Understanding
the Origin of the RNA World," in "The RNA World,"
Gesteland R.F. & Atkins J.F., eds.
Joyce and Orgel suggest that one must reject
the myth of a self-replicating RNA molecule that arose de novo
from a soup of random polynucleotides. Not only is such a notion
unrealistic in light of our current understanding of prebiotic
chemistry, but it should strain the credulity of even an optimist's
view of RNA's catalytic potential. If you doubt this, ask yourself
whether you believe that a replicase ribozyme would arise in a
solution containing nucleoside 5'-diphosphates and
polynucleotide phosphorylase!
Joyce G.F. & Orgel L.E.,
"Prospects for Understanding the Origin
of the RNA World," in "The RNA World,"
Gesteland R.F. & Atkins J.F., eds.
==
you may wish to peruse this
review [abridged by me for space]
Self-organizing biochemical cycles
Leslie E. Orgel*
Salk Institute for Biological Studies,
10010 North Torrey Pines Road,
La Jolla, CA 92037-1099
*E-mail:
or...@salk.edu.
Contributed by Leslie E. Orgel
Accepted August 24, 2000.
Abstract
I examine the plausibility of theories that postulate the development
of complex chemical organization without requiring the replication
of genetic polymers such as RNA. One conclusion is that theories
that involve the organization of complex, small-molecule metabolic
cycles such as the reductive citric acid cycle on mineral surfaces
make unreasonable assumptions about the catalytic properties of
minerals and the ability of minerals to organize sequences of
disparate reactions. Another conclusion is that data in the Beilstein
Handbook of Organic Chemistry that have been claimed to support
the hypothesis that the reductive citric acid cycle originated as a
self-organized cycle can more plausibly be interpreted
in a different way.
<...>
One possible saving hypothesis is that the molecules that
are the carriers of the cycle are also catalysts for the difficult
reactions of the cycle. Unfortunately, catalytic reactions of
the required kind in aqueous solution are virtually unknown;
there is no reason to believe, for example, that any intermediate
of the citric acid cycle would specifically catalyze any reaction
of the citric acid cycle. The explanation of this is simple:
noncovalent interactions between small molecules in
aqueous solution are generally too weak to permit large
and regiospecific catalytic accelerations. To postulate
one fortuitously catalyzed reaction, perhaps catalyzed
by a metal ion, might be reasonable, but to postulate
a suite of them is to appeal to magic.
<...>
The idea that a complex polymerization reaction such as the
formose reaction or the polymerization of hydrogen cyanide
is likely to simplify to a specific cycle under the influence of
autocatalysis in aqueous solution is implausible. It is not
logically impossible that such an autocatalytic cycle exists,
but because it seems very unlikely from what we already
know about the chemistry of aqueous solutions,
the burden of proof lies with the proposers of such cycles.
W�chtersh�user has put forward a very specific hypothesis that,
if correct, would overcome all of the difficulties discussed above.
In a scenario that he describes as �Two-Dimensional Chemi-Autotrophic
Surface Metabolism in an Iron-Sulfur World� (9), he proposes that
the reductive citric acid cycle and much other organized, nonenzymatic
chemistry occurred on the primitive earth, but on the surface of
iron sulfide minerals rather than in aqueous solution. W�chtersh�user
points out that the conversion of ferrous sulfide (FeS) to pyrites
(FeS2)
in the presence of hydrogen sulfide makes available reducing power
equivalent to molecular hydrogen. This reducing power could be used
to convert carbon dioxide to carbon-containing metabolites.
W�chtersh�user also claims that the surface of iron sulfide would
constrain the spatial distribution and orientation of the newly
formed products of reduction in such a way as to support
complex sequences of metabolic reactions.
<...>
In summary, it seems very likely that minerals played an important part
in prebiotic chemistry, both as simple adsorbents and as catalysts.
A single mineral is unlikely to have functioned as a specific catalyst
for several unrelated reactions. Even if the members of a suite of
minerals could each catalyze one step in a complex cycle, it does not
seem likely that the cycle would self-organize on their surfaces.
Any suite of minerals that included catalysts for each step of the cycle
would be likely to include, in addition, catalysts for reactions that
disrupt the cycle. Efficient transport of the intermediates from one
catalytic mineral to another would also present severe problems.
There is at present no reason to expect that multistep cycles
such as the reductive citric acid cycle will self-organize
on the surface of FeS/FeS2 or some other mineral.
While it seems almost impossible that a cycle of reactions as
complicated as the reductive citric acid cycle could self-organize
on a mineral surface, W�chterh�user's suggestion does raise an
interesting and important question. How much self-organization
is it reasonable to expect on a mineral surface in the absence
of evolved, informational catalysts? Clearly, a simple surface
could reasonably be expected to carry out a series of reactions of
essentially the same type, say a series of aldol and reverse
aldol reactions of the type involved in the formose reaction [.],
or a series of reductions of the type involved in the reductive
citric acid cycle. It is not clear that any surface is likely
to catalyze two or more unrelated chemical reactions, but it
would be interesting to try to discover multifunctional surfaces.
The problem of stereospecificity of a sequence of similar reactions
in aqueous solution or on a mineral surface is equally difficult.
Repetition of some basic reaction with constant stereospecificity
does not seem unlikely, because it is routinely achieved by
polymer chemists. Catalysis of a sequence of reactions, each
with a different defined stereospecificity, seems much less plausible.
Just how far one can go in the direction of self-organization
on mineral surfaces is a question for the future. One can be sure
that the complete reverse citric acid cycle is out of range, but
it is not obvious that some much simpler cycle relevant to the
origin of life is impossible. Huber and W�chtersh�user have
noted the possibility of such a cycle in a footnote added in
proof to ref. 23, but it is not clear whether this cycle is
intended to augment the citric acid cycle or replace it.
The demonstration of a simple specific version of the
formose reaction, for example, would be important, but
studies of the specificity of the formose reaction when
catalyzed by minerals have been disappointing (23).
23. Schwartz A W, de Graaf R M. J Mol Evol. 1993;36:101�106.
<...>
The novel, potentially replicating polymers that have been described
up to now, like the nucleic acids, are formed by joining together
relatively complex monomeric units. It is hard to see how any could
have accumulated on the early earth. A plausible scenario for the
origin of life must, therefore, await the discovery of a genetic polymer
simpler than RNA and an efficient, potentially prebiotic, synthetic
route to the component monomers. The suggestion that relatively
pure, complex organic molecules might be made available in large
amounts via a self-organizing, autocatalytic cycle might, in principle,
help to explain the origin of the component monomers. I have
emphasized the implausibility of the suggestion that complicated
cycles could self-organize, and the importance of learning more
about the potential of surfaces to help organize simpler cycles.
===
==
Postulate 2: Beta-D ribonucleotides spontaneously form polymers
linked together by 3', 5'-phosphodiester linkages (i.e., they link to
form molecules of RNA).
Joyce and Orgel discuss candidly the problems with this postulate.
They note that nucleotides do not link unless there is some type of
activation of the phosphate group. The only effective activating groups
for the nucleotide phosphate group (imidazolides, etc.), however, are
those that are totally implausible in any prebiotic scenario. In living
organisms today, adenosine-5'-triphosphate (ATP) is used for activation
of nucleoside phosphate groups, but ATP would not be available
for prebiotic syntheses. Joyce and Orgel note the possible use
of minerals for polymerization reactions, but then express
their doubts about this possibility:
=================================================
Whenever a problem in prebiotic synthesis seems intractable,
it is possible to postulate the existence of a mineral that
catalyzes the reaction...such claims cannot easily be refuted.
=================================================
-
G.F. Joyce and L.E. Orgel,
"Prospects for understanding the origin of the RNA World,"
in The RNA World, eds. R.F. Gesteland and J.F. Atkins
(Cold Spring Harbor, NY:
Cold Spring Harbor Laboratory Press, 1993), pp. 1-25.
===
Gerald Joyce and Leslie Orgel-two scientists who
have worked on the origin of life problem-call RNA
`the prebiotic chemist's nightmare.
`Scientists interested in the origins of life seem to divide
neatly into two classes. The first, usually but not always
molecular biologists, believe that RNA must have been the
first replicating molecule and that chemists are exaggerating
the difficulties of nucleotide synthesis.... The second
group of scientists are much more pessimistic. They believe
that the de novo appearance of oligonucleotides on the
primitive earth would have been a near miracle.
(The authors subscribe to this latter view).
Time will tell which is correct.
[Joyce G.F. & Orgel L.E., "Prospects for Understanding the Origin
of the RNA World," in "The RNA World," Gesteland R.F. & Atkins J.F.,
eds. Cold Spring Harbor Laboratory Press,
Cold Spring Harbor NY, 1993, p.19]
Even if the miracle-like coincidence should occur and RNA be produced,
however, Joyce and Orgel see nothing but obstacles ahead. In an article
section entitled "Another Chicken-and-Egg Paradox" they write the
following:
This discussion ... has, in a sense, focused on a straw man:
the myth of a self-replicating RNA molecule that arose de novo
from a soup of random polynucleotides. Not only is such a notion
unrealistic in light of our current understanding of prebiotic
chemistry, but it should strain the credulity of even an optimist's
view of RNA s catalytic potential.... Without evolution it appears
unlikely that a self-replicating ribozyme could arise, but without
some form of self-replication there is no way to conduct an
evolutionary search for the first, primitive self-replicating
ribozyme.' [Joyce & Orgel, 1993, p.13]
===
Incubation of the pool RNA...led to rapid and extensive aggregation;
more than half of the pool RNA precipitated when incubated for 90
minutes at 37� C in high concentrations of Mg2+ and monovalent
ions...and
precipitation was even more rapid at higher temperatures. It appears
that conditions that favor RNA intramolecular structure also stabilize
intermolecular interactions; as molecules find regions of
complementarity with more than one other molecule, RNA networks
form and eventually become too large to remain in solution.
David P. Bartel and Jack W. Szostak,
"Isolation of New Ribozymes from a
Large Pool of Random Sequences,
" Science 261 (1993): 1411-1418; p. 1412.
===