ABIOGENESIS

By Ajay Adithya

CLASS 12-A
[Company address]
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Content
1) Introdution
2) Current models
3) Chemical origin of organic molecules
4) An RNA World first?
5) Gradual build-up of complexity
6) Specificity of chemical reactions and the
‘metabolism-first’ scenario
7) A primordial protoplasmic globule
8) Conclusion
9) Reference
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Introduction:
Abiogenesis, or informally the origin of life, is the natural process by which life has
arisen from non-living matter, such as simple organic compounds. While the details
of this process are still unknown, the
prevailing scientific hypothesis is that the
transition from non-living to living
entities was not a single event, but a
gradual process of increasing complexity
that involved molecular self-replication,
self-assembly, autocatalysis, and the
emergence of cell membranes. Although
the occurrence of abiogenesis is
uncontroversial among scientists, there is
The earliest known life-forms on Earth are
putative fossilized microorganisms, found in
no single, generally accepted model for
hydrothermal vent precipitates, that may have the origin of life, and this article presents
lived as early as 4.28 billion years ago, several principles and hypotheses for how
relatively soon after the oceans formed 4.41 abiogenesis could have occurred.
billion years ago, and not long after the
formation of the Earth 4.54 billion years ago

Researchers study abiogenesis through a

combination of molecular biology, paleontology, astrobiology, oceanography,
biophysics, geochemistry and biochemistry, and aim to determine how pre-life
chemical reactions gave rise to life. The study of abiogenesis can be geophysical,
chemical, or biological, with more recent approaches attempting a synthesis of all
three, as life arose under conditions that are strikingly different from those on Earth
today. Life functions through the specialized chemistry of carbon and water and
builds largely upon four key families of chemicals: lipids (fatty cell walls),
carbohydrates (sugars, cellulose), amino acids (protein metabolism), and nucleic
acids (self-replicating DNA and RNA). Any successful theory of abiogenesis must
explain the origins and interactions of these classes of molecules. Many approaches
to abiogenesis investigate how self-replicating molecules, or their components, came
into existence. Researchers generally think that current life on Earth descends from
an RNA world, although RNA-based life may not have been the first life to have
existed.
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The classic 1952 Miller–Urey experiment and similar research demonstrated that
most amino acids, the chemical constituents of the proteins used in all living
organisms, can be synthesized from inorganic compounds under conditions intended
to replicate those of the early Earth. Scientists have proposed various external
sources of energy that may have triggered these reactions, including lightning and
radiation. Other approaches ("metabolism-first" hypotheses) focus on understanding
how catalysis in chemical systems on the early Earth might have provided the
precursor molecules necessary for self-replication. Complex organic molecules
occur in the Solar System and in interstellar space, and these molecules may have
provided starting material for the development of life on Earth.

The biochemistry of life may have begun shortly after the Big Bang, 13.8 billion
years ago, during a habitable epoch when the age of the universe was only 10 to 17
million years. The panspermia hypothesis suggests that microscopic life was
distributed to the early Earth by space dust, meteoroids, asteroids and other small
Solar System bodies and that life may exist throughout the universe. The panspermia
hypothesis proposes that life originated outside the Earth, but does not definitively
explain its origin.

Earth remains the only place in the universe known to harbor life, and fossil evidence
from the Earth informs most studies of abiogenesis. The age of the Earth is about
4.54 billion years; the earliest undisputed evidence of life on Earth dates from at
least 3.5 billion years ago, and possibly as early as the Eoarchean Era (between 3.6
and 4.0 billion years ago), after geological crust started to solidify following the
molten Hadean Eon. In May 2017 scientists found possible evidence of early life on
land in 3.48-billion-year-old geyserite and other related mineral deposits (often
found around hot springs and geysers) uncovered in the Pilbara Craton of Western
Australia. However, a number of discoveries suggest that life may have appeared on
Earth even earlier. As of 2017, microfossils, or fossilized microorganisms, within
hydrothermal-vent precipitates dated from 3.77 to 4.28 billion years old found in
Quebec, Canadian rocks may harbor the oldest record of life on Earth, suggesting
life started soon after ocean formation 4.4 billion years ago. According to biologist
Stephen Blair Hedges, "If life arose relatively quickly on Earth … then it could be
common in the universe."
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Current models:
There is no single, generally accepted model for the origin of life. Scientists have
proposed several plausible hypotheses, which share some common elements. While
differing in the details, these hypotheses are based on the framework laid out by
Alexander Oparin (in 1924) and by J. B. S. Haldane (in 1925), who postulated the
molecular or chemical evolution theory of life. According to them, the first
molecules constituting the earliest cells "were synthesized under natural conditions
by a slow process of molecular evolution, and these molecules then organized into
the first molecular system with properties with biological order". Oparin and
Haldane suggested that the atmosphere of the early Earth may have been chemically
reducing in nature, composed primarily of methane (CH4), ammonia (NH3), water
(H2O), hydrogen sulfide (H2S), carbon dioxide (CO2) or carbon monoxide (CO), and
phosphate (PO43-), with molecular oxygen (O2) and ozone (O3) either rare or absent.
According to later models, the atmosphere in the late Hadean period consisted
largely of nitrogen (N2) and carbon dioxide, with smaller amounts of carbon
monoxide, hydrogen (H2), and sulfur compounds; while it did lack molecular oxygen
and ozone, it was not as chemically reducing as Oparin and Haldane supposed. In
the atmosphere proposed by Oparin and Haldane, electrical activity can produce
certain small molecules (monomers) of life, such as amino acids. The Miller–Urey
experiment reported in 1953 demonstrated this.

Bernal coined the term biopoiesis in 1949 to refer to the origin of life. In 1967, he
suggested that it occurred in three "stages":
 the origin of biological monomers
 the origin of biological polymers
 the evolution from molecules to cells
Bernal suggested that evolution commenced between stages 1 and 2. Bernal regarded
the third stage – discovering methods by which biological reactions were
incorporated behind a cell's boundary – as the most difficult. Modern work on the
way that cell membranes self-assemble, and the work on micropores in various
substrates may be a halfway house towards the development of independent free-
living cells.
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The chemical processes that took place on the early Earth are called chemical
evolution. Since the end of the nineteenth century, 'evolutive abiogenesis' means
increasing complexity and evolution of matter from inert to living state. Both
Manfred Eigen and Sol Spiegelman demonstrated that evolution, including
replication, variation, and natural selection, can occur in populations of molecules
as well as in organisms. Spiegelman took advantage of natural selection to
synthesize the Spiegelman Monster, which had a genome with just 218 nucleotide
bases, having deconstructively evolved from a 4500-base bacterial RNA. Eigen built
on Spiegelman's work and produced a similar system further degraded to just 48 or
54 nucleotides – the minimum required for the binding of the replication enzyme.

Following on from chemical evolution came the initiation of biological evolution,

which led to the first cells. No one has yet synthesized a "protocell" using simple
components with the necessary properties of life (the so-called "bottom-up-
approach"). Without such a proof-of-principle, explanations have tended to focus on
chemosynthesis. However, some researchers work in this field, notably Steen
Rasmussen and Jack W. Szostak. Others have argued that a "top-down approach" is
more feasible. One such approach, successfully attempted by Craig Venter and
others at J. Craig Venter Institute, involves engineering existing prokaryotic cells
with progressively fewer genes, attempting to discern at which point the most
minimal requirements for life are reached.

The NASA strategy on abiogenesis states that it is necessary to identify interactions,

intermediary structures and functions, energy sources, and environmental factors
that contributed to the diversity, selection, and replication of evolvable
macromolecular systems. Emphasis must continue to map the chemical landscape of
potential primordial informational polymers. The advent of polymers that could
replicate, store genetic information, and exhibit properties subject to selection likely
was a critical step in the emergence of prebiotic chemical evolution.
In October 2018, researchers at McMaster University announced the development
of a new technology, called a Planet Simulator, to help study the origin of life on
planet Earth and beyond. It consists of a sophisticated climate chamber to study how
the building blocks of life were assembled and how these prebiotic molecules
transitioned into self-replicating RNA molecules.
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Chemical origin of organic molecules:

The elements, except for hydrogen and helium, ultimately derive from stellar
nucleosynthesis. On 12 October 2016, astronomers reported that the very basic
chemical ingredients of life—the carbon-hydrogen molecule (CH, or methylidyne
radical), the carbon-hydrogen positive ion (CH+) and the carbon ion (C+)—are
largely the result of ultraviolet light from stars, rather than other forms of radiation
from supernovae and young stars, as thought earlier. Complex molecules, including
organic molecules, form naturally both in space and on planets. There are two
possible sources of organic molecules on the early Earth:
 Terrestrial origins – organic molecule synthesis driven by impact shocks or
by other energy sources (such as UV light, redox coupling, or electrical
discharges; e.g., Miller's experiments)
 Extraterrestrial origins – formation of organic molecules in interstellar dust
clouds, which rain down on planets.
Based on recent computer model studies, the complex organic molecules necessary
for life may have formed in the protoplanetary disk of dust grains surrounding the
Sun before the formation of the Earth. According to the computer studies, this same
process may also occur around other stars that acquire planets. (Also see
Extraterrestrial organic molecules).

Estimates of the production of organics from these sources suggest that the Late
Heavy Bombardment before 3.5 Ga within the early atmosphere made available
quantities of organics comparable to those produced by terrestrial sources.

It has been estimated that the Late Heavy Bombardment may also have effectively
sterilized the Earth's surface to a depth of tens of metres. If life evolved deeper than
this, it would have also been shielded from the early high levels of ultraviolet
radiation from the T Tauri stage of the Sun's evolution. Simulations of
geothermically heated oceanic crust yield far more organics than those found in the
Miller-Urey experiments. In the deep hydrothermal vents, Everett Shock has found
"there is an enormous thermodynamic drive to form organic compounds, as seawater
and hydrothermal fluids, which are far from equilibrium, mix and move towards a
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more stable state." Shock has found that the available energy is maximized at around
100–150 degrees Celsius, precisely the temperatures at which the hyperthermophilic
bacteria and thermoacidophilic archaea have been found, at the base of the
phylogenetic tree of life closest to the Last Universal Common Ancestor (LUCA).

The accumulation and concentration of organic molecules on a planetary surface is

also considered an essential early step for the origin of life. Identifying and
understanding the mechanisms that led to the production of prebiotic molecules in
various environments is critical for establishing the inventory of ingredients from
which life originated on Earth, assuming that the abiotic production of molecules
ultimately influenced the selection of molecules from which life emerged.

An RNA World first?

It is now widely agreed that at the origin of life there was not the current
DNA/(RNA)/protein system for gene information on one hand and catalysis,

A cladogram demonstrating extreme hyperthermophiles at the base of the phylogenetic tree

of life
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regulation, and structural function on the other. It would beg the question, what came
first, protein or DNA? Protein catalysis without gene information, which allows it to
be maintained and propagated, is not sufficient in the long term, and DNA gene
information without catalysis, necessary for the function of life, would be useless as
well.

Instead, it is assumed that RNA acted as a precursor of both protein and DNA, in the
sense that it can serve both as catalyst (like protein enzymes) and as carrier of genetic
information. Even in the modern cell ribozymes (catalytic RNAs) still play a vital,
albeit limited, role. In the ribosome, the synthesis of the peptide chains of proteins
from RNA code is accomplished by ribozymes. They also catalyze splicing of RNA.

The hypothesis that a so-called RNA World was involved in the early evolutionary
stages of life is now an almost universally held view. Could this RNA World have
stood at the ultimate origin of life? This is currently still an open question. The RNA
system may be too complex to have arisen without synthesis by a genetic precursor
or prior enzyme-less metabolism (options discussed below). Yet while there are still
substantial problems, there are now good leads for simple, spontaneous processes on
the early Earth for both the synthesis of nucleotides and their concatenation to
oligonucleotides.

For a long time the synthesis of RNA monomers under prebiotic conditions appeared
to be a fundamental problem since the condensation of sugar (ribose) and nucleobase
(purines and pyrimidines) does not work. The prebiotic synthesis of purine
ribonucleotides is still unclear, yet recently a breakthrough has been made with
regard to the synthesis of pyrimidine ribonucleotide monomers (which incorporate
cytosine and uracil). It now appears in principle to be solved, in a completely
unexpected manner. The study by the group of John Sutherland shows how nature
could have spontaneously assembled pyrimidine ribonucleotide monomers from
prebiotically plausible molecules through intermediates that contribute atoms to both
the sugar and base portions of the ribonucleotides, thus avoiding a condensation step
of sugar and base altogether (Fig.1). See also Nature News for the impact of these
findings. While a good pathway for synthesis of purine ribonucleotides
(incorporating adenine and guanine) still remains to be found, Jack Szostak argues
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in a comment accompanying the article that “it is precisely because this work opens
up so many new directions for research that it will stand for years as one of the great
advances in prebiotic chemistry”.

Figure 1. Pyrimidine ribonucleotide assembly options. Previously assumed synthesis of b-

ribocytidine-2’,3’-cyclic phosphate 1 (blue; note the failure of the step in which cytosine 3
and ribose 4 are proposed to condense together) and the successful new synthesis described
here (green). p, pyranose; f, furanose.
(5 = Cyanoacetaldehyde, 6 = urea 6, cyanoacetylene 7, 8= cyanamide, 9 = glyceraldehyde, 10
= glycolaldehyde, 11 = 2-amino-oxazole, 12= pentose amino-oxazoline, arabinose derivative,
13 = anhydroarabinonucleoside)
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With regard to the concatenation of nucleotides to oligonucleotides there is progress

as well. The polymerization of chemically-activated RNA monomers can take place
on the mineral surfaces of montmorillonite clay, generating polymer chains of up to
50-mers. The pyrimidine ribonucleotide monomers from the new synthesis are also
activated (they contain cyclic phosphate), which may allow for similar
polymerization.

The group of David Deamer has shown that the synthesis of RNA-like polymers can
even occur from non-activated mononucleotides within phospholipids vesicles, due
to the chemical potential of fluctuating anhydrous and hydrated conditions, with heat
providing activation energy during rehydration. Such conditions could have existed
around hot springs on the prebiotic Earth. The lipids also provide a structurally
organizing microenvironment that imposes order on mononucleotides. In this
experimental setup, oligomers of up to 100 nucleotides can be formed non-
enzymatically. It remains to be seen if prebiotically plausible fatty acid vesicles
could have the same effect on RNA synthesis (with this a self-replicating RNA
molecule would also have been pre-packaged for further evolution, cf. below).
Effective polymerization of monomers that are activated might be aided by a
structurally organizing microenvironment within vesicles as well.

However, while these reactions make RNA-like polymers they do not yet solve the
problem of the stereospecific 3’-5’ concatenation of monomers (Orgel 2004), found
in all living organisms. Both the lipid-assisted synthesis and polymerization on
montmorillonite produce mixes of 2’-5’ and 3’-5’ bonds. Yet in the latter there is a
preference towards 3’-5’ bonds (up to 74 %) which is promising. The authors of the
study (Huang and Ferris 2006) argue that a higher proportion of 3’-5’ links could
have resulted in the more rapid evolution to all 3’-5’ phosphodiester bonds during
replication of oligomers, suggesting that perhaps complete 3’-5’ specificity of bonds
within the first replicating RNA molecule may not have been required. This scenario
may not be impossible, given that RNA usually forms more irregular secondary
structures than DNA with its double helix, for which absolute stereospecificity of
synthesis is mandatory. In the study, different kinds of chemical activation of RNA
monomers yielded different preferences for 3’-5’ concatenation. It remains to be
seen how specific for 3’-5’ bonds concatenation of monomers from activation with
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cyclic phosphate will be, the kind of activation reported in the new synthesis of
pyrimidine ribonucleotide monomers.

Because of the difficulties of the synthesis of RNA nucleotides and oligonucleotides

– which, however, appear now considerably less severe than just a few years ago,
given the new findings – several alternatives to RNA as the first genetic system have
been proposed, which may have preceded it. Peptide nucleic acid (PNA), threose
nucleic acid (TNA) and peptides in which D- and L-amino acids alternate that
incorporate standard nucleic-acid bases (ANAs) are discussed in. An even simpler
system is glycerol nucleic acid. A highly interesting and chemically appealing, yet
still untested idea is the PAH World (PAH = polycyclic aromatic hydrocarbons),
developed by S. Platts and described in and also at Wikipedia and at pahworld.com.

Other difficulties are that a ribozyme (catalytic RNA) that can copy itself completely
has not yet been found – so far, a 200 base ribozyme can copy around 20 bases of
its sequence with high fidelity, an improvement on. A solution for the problem of
copying a long ribozyme sequence has been proposed in Szostak et al. (2001);
experiments will have to show if it is feasible. Also, “the formidable problem of
separating the double-stranded product of the copying reaction so as to permit a
second round of copying would remain to be solved”. Recent findings suggest that
this problem may be addressed by thermal cycling, analogous to the polymerase
chain reaction (PCR), which may have been a possibility under plausible prebiotic
conditions.

Gradual build-up of complexity:

Let us assume the plausible scenario that either RNA was directly synthesized, see
above, so that out of a large pool of random RNAs a self-replicating RNA molecule
could arise, or that such synthesis was accomplished by a precursor genetic/catalytic
system (possibly on the surface of minerals0. Since fatty acids could have been
available in the environment, a primitive fatty acid membrane could have surrounded
the first self-replicating RNA molecules (due to their molecular properties, fatty
acids can form vesicles spontaneously); this would not have allowed passage of the
RNA polymers so that they would have stayed together, but would have let the much
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smaller nucleotides through, fed in from spontaneous prebiotic synthesis or from a

precursor genetic/catalytic system. Such a membrane would have had different
characteristics of semi-permeability than modern lipid membranes, where a lot of
molecule transfer is regulated through protein channels.

The group of Jack Szostak has performed extensive and plausible studies that these
fatty acid vesicles as containers for RNA would have allowed growth and replication
merely by physico-chemical mechanisms, until a more sophisticated membrane
machinery, steered by the cell itself and more resembling what is found in current
organisms, would have taken their place.

While in earlier studies more extreme conditions and sheer forces were required for
vesicle division, also leading to the loss of a substantial fraction of vesicle contents,
a new study shows a solution to these problems. It uses multilamellar vesicles
(vesicles with several layers of lipid membrane) that form spontaneously by the
rehydration of fatty acid films or by the acidification of a concentrated solution of
fatty acid micelles. Once multilamellar vesicles are formed, spontaneous further
incorporation of fatty acid micelles into them causes, via an unexpected mechanism,
the formation of strongly elongated, thread-like vesicles. After subjection to mild
shear forces these divide into several, again round, small daughter vesicles that
preserve RNA contents well.

The group of Szostak also has demonstrated that nucleotides can pass through
prebiotically plausible fatty-acid based vesicles and that non-enzymatic template
copying of a model oligo dC DNA template can take place within them , which, in
connection with the studies of vesicle growth and division, reveals in principle how
a heterotrophic protocell may have functioned (Fig. 2). Furthermore, they showed
that prebiotically plausible model membranes are surprisingly thermostable,
allowing them to tolerate at least short periods of temperatures of up to 100°C.
Thermal cycling might have been possible near or within the surface of hydrothermal
vents or hot springs (for thermal convection within hydrothermal pores). This might
solve the thorny issue of separating the double-stranded product of the copying
reaction for further replication. Thermal cycling could have allowed for this
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separation of copying products at high temperatures, and copying at lower ones,

analogous to the polymerase chain reaction (PCR).

Figure 2. Conceptual model of a heterotrophic protocell. Growth of the protocell membrane

results from the incorporation of environmentally supplied amphiphiles, whereas division may
be driven by intrinsic or extrinsic physical forces. Externally supplied activated nucleotides
permeate across the protocell membrane and act as substrates for the copying of internal
templates. Complete template replication followed by random segregation of the replicated
genetic material leads to the formation of daughter protocells.

Extrapolating from all the above data, inside fatty-acid vesicles the first self-
replicating RNA molecule could have started copying itself. During copying, various
things would have been possible. High-fidelity copies would have yielded the same
self-replicating molecule. Copies with errors would mostly have resulted in RNA
that was non-functional, but in a minority of cases, they could have yielded RNA
that copied itself faster. It has been shown that RNA/vesicle systems that contain
more genetic material (which would have resulted from faster RNA replication)
develop more internal tension than neighboring vesicles that do not contain as much
RNA, and draw membrane material from them. Importantly, this would have
allowed for natural selection of vesicles by competition even in the absence of the
ability to synthesize their own membrane components and therefore to directly
control their own growth. Thus, for the first time, a system would have had the ability
to undergo Darwinian evolution by natural selection acting on variation. This would
have been a new and crucial emergent property arising at the transition from non-
life to life.
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A small portion of other copying errors (again, most substantial errors would
probably have resulted in non-functional molecules, but those would have been
filtered out by natural selection) could have led to RNA molecules with yet other,
entirely different catalytic properties than the copying function. A new property
could have allowed the RNA/vesicle system to even better compete for resources:
just like in the case of the RNA molecules featuring the better copying function, the
RNA would have evolved. The copy function of the parent molecules would
probably have acted on these daughter molecules as well (like an RNA polymerase
enzyme that copies any RNA). RNA/vesicle systems that had the altered RNA
molecules with the new beneficial function, in addition to retaining the RNA with
the copy function, would have been favored by natural selection. Finally, through
reiteration of such processes, a series of new catalytic properties could, for example,
have allowed the RNA pool within the vesicles to start making its own nucleotides.
Would it then have been self-sufficient? To a certain degree, yes. Could this have
been the first primitive cell? Why not?

It is just that in this scenario, the initial metabolism would have been much simpler
than today’s metabolism: Among others, energy metabolism could have been
replaced by passage of activated building blocks for molecules from the outside
environment into the vesicle (in a sense providing a preliminary substitute for
modern-day ATP production, a possibility in view of the simple metabolism), and
lipid metabolism, building of membrane structure and its regulation during
replication would have been replaced by simple vesicles plainly obeying physico-
chemical forces.

In other words: the cell would have depended more on the outside world, but for
what it was doing, it was to a certain degree self-sufficient (today’s organisms also
need sustenance from the outside world of course, in the form of nutrients). On the
other hand, the dependence of the cell on the outside world would also have been
possible in a more immediate manner. A modern cell cannot, for example, use fatty
acids from the outside in a way that they are directly incorporated as membrane
elements.
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Earlier we had asked: How could a complex network of more than 200 essential
proteins, as it is found in today’s most elementary cells, have arisen on its own?

The key to answering this question appears the combination of the above two
attributes in the primitive cell: more direct dependence on the outside world than the
modern cell, but also a greater ability to show such dependence – by accepting
molecular building blocks as such without having to convert nutrients into them.
Starting with these characteristics and gradually moving on from there, evolution
indeed could have ‘eased’ the cellular system into more complexity.

Perhaps lipid synthesis, in a precursor form of modern synthesis, could have made
the system more independent. The RNA system could have, bit by bit, ‘invented’
protein synthesis – as mentioned, the modern ribosomes still contain ribozymes
(catalytic RNA) that catalyze the formation of peptide bonds which eventually result
in proteins. In a compelling study the authors propose a stepwise model for the origin
of the protein translation system, in which each step confers a distinct advantage
onto an ensemble of co-evolving genetic elements. The goal of development of
translation would not have been required, a foresight which evolution does not have.
The initial cause for the emergence of translation would have been the ability of
amino acids and peptides to stimulate reactions catalyzed by ribozymes (for peptides
experimentally shown, see Robertson et al. 2004). Even if it will turn out that several
steps in the evolution of translation probably have been different from the proposed
model, the study clearly demonstrates that there is nothing in the emergence of the
translation system that would represent a case of ‘irreducible complexity’, incapable
of being subject to stepwise Darwinian evolution.

A recent study, based on analysis of the interdependence of elements of the

macromolecule, shows a step-by-step evolution of the ribosome on the structural
level, beginning from a very small core, the peptide transpeptidation centre. Further
layers were added from the outside one by one, until the current complex
macromolecule emerged. Each of these layers is structurally connected only to the
respective previous one, and could be removed in the model without destroying the
integrity of the inner layers (like the peeling of an onion), showing that there was no
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need for the entire molecule to emerge at once. This establishes the lack of
‘irreducible complexity’ of the translational machinery from another perspective.

Finally, complex metabolism could have been achieved and the transition to the
modern DNA/(RNA)/protein world. The dualism DNA/protein of course is a source
of complexity in itself, one that is lacking in an RNA-only organism.

What about the difficult issue of a genome which holds all genes together? It might
have been that in the first primitive cells RNAs were ligated ‘by accident’ step by
step, one by one, into forming a genome precursor and that each such step conferred
an advantage in natural selection over competitor cells, since genes would not have
been lost anymore during cell division, and replication would have been
synchronized. Over time, an entire small RNA genome potentially could have
organized itself in this manner, until mechanisms for internal expansion, like they
are found in modern genomes, could have taken over, e.g. gene duplication and
variation of the duplicated gene.

Certainly, reading of a string of ligated RNA as several single genes would have
required that the primitive cellular mechanism would have come across a way to
recognize beginning and end of a sequence. Promoter regions and start/stop codons,
in the form they are used in protein-coding genes, would not have been present in a
primitive RNA organism.

While lack of replication fidelity would have been an issue in primordial RNA
genomes, analysis of experimental mutation studies on ribozymes indicates that an
RNA genome may nonetheless have grown as large as 100 genes. The RNA genome
could, bit by bit, have been replaced by a DNA genome, a selectable advantage that
primordial cells would have encountered by chance.

As for the universal genetic code: there is evidence that, until the last common
ancestor, the genetic code was selected to a substantial extent for error minimization,
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thus is not arbitrary. Yet in part it is probably also ‘frozen accident’ since the
selection for this feature appears not to be maximal.

In summary, based on available data a spontaneous origin of life as simple ‘cells’

containing a single genetic polymer, upon which natural selection could act, is
feasible. A gradual evolutionary transition from these to common cellular
complexity would have been possible.

Specificity of chemical reactions and the ‘metabolism-first’

scenario:
Some extend the above findings from deep-sea hydrothermal vents to a variant of
the ‘metabolism-first’ scenario as opposed to the ‘gene-first’ scenario described
above, a hypothesis that claims that complex metabolic cycles could have self-
organized, independent of a genetic system which is capable of providing polymer
catalysts. According to this hypothesis, only via such a stable metabolism the
synthesis of nucleotides and oligonucleotides, necessary for the inception of the
RNA world, would have been possible – yet due to the here discussed recent findings
spontaneous prebiotic RNA synthesis is now becoming far more likely than when
these ‘metabolism-first’ scenarios were originally proposed.

In the same publications in which Günter Wächtershäuser had predicted the

synthesis of organic molecules under conditions as found in hydrothermal vents,
predictions that have been experimentally confirmed, he also introduced a metabolic
model. This inventive and detailed hypothesis integrates in an impressive manner a
multitude of observations in the field of chemistry. It suggests that the beginning of
life was what has been termed a ‘flat life’, an elaborate two-dimensional metabolism
on mineral surfaces of deep-sea hydrothermal vents; this also addresses the ‘dilution
problem’ by concentrating all chemistry on the surface. Central to this and other
‘metabolism-first’ hypotheses is the reductive citric acid cycle which provides a core
mechanism of useful biomolecules from CO2.
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However, the unfolding of this and related scenarios would require a surprising lack
of side reactions (while a residual small level of side reactions might favor
evolutionary development). It is not easy to see how the extraordinarily high
specificity of chemical reactions, required for complex sequences of reactions and
metabolism – for the functioning of life –, would in general be possible without
catalytic polymers featuring a three-dimensional substrate pocket. These are only
provided by a ‘gene-first’ scenario. Leslie Orgel comments on the issue as follows:

“There is no agreement on the extent to which metabolism could develop

independently of a genetic material. In my opinion, there is no basis in known
chemistry for the belief that long sequences of reactions can organize spontaneously
– and every reason to believe that they cannot. The problem of achieving sufficient
specificity, whether in aqueous solution or on the surface of a mineral, is so severe
that the chance of closing a cycle of reactions as complex as the reverse citric acid
cycle, for example, is negligible. The same, I believe, is true for simpler cycles
involving small molecules that might be relevant to the origins of life and also for
peptide-based cycles.”

Thus it appears reasonable to assume that the development of metabolic cycles and
pathways would have required genetic/catalytic polymers – even though, obviously,
opinions are divided on the issue.

Stuart Kauffman’s large autocatalytic sets may be far too optimistic for the same
reason. Autocatalytic sets may have a better chance of being realized when they are
small.

Newer developments, however, may be seen to raise the possibility that the
‘metabolism-first’ scenario is realistic after all. It was found that three of the five
reductive steps of the reverse Krebs cycle (Fig. 3) could be driven by ZnS particles
(providing reducing power of conduction-band electrons and believed to have been
prevalent in the waters of the early Earth) under the influence of UV light. The
conversions of oxalacetate to malate, and of fumarate to succinate proceeded at
astonishing yields (75 % and 95 %, respectively), which may be close to sufficient.
 19

The conversion of succinate to oxoglutarate also proceeded, albeit at a low rate of

2.5 %. The authors suggest that a more complex mineral assemblage than ZnS alone
may drive the entire suite of reactions.

Figure 3. Reverse Krebs cycle. Highlighted are the five reduction reactions (labeled 1-5).

Of high interest are also recent findings that have been reported (Robinson 2005) to
give hope to adherents of the ‘metabolism-first’ model. It has been shown (Cordova
et al. 2005a) that such simple organic molecules as single amino acids can catalyze
the stereospecific synthesis of sugars from simple starting materials with enzyme-
like specificity, albeit only in organic solvents. For example, either L- or D-
enantiomers of certain amino acids (with serine among those, see below) can trigger
formation of a certain type of sugar not just with excellent chemoselectivity (i.e.
avoiding unwanted side reactions), but also the formation of one out of 16 possible
enantiomers of this sugar with approx. 99 % stereospecificity. These reactions are
based on the principle of asymmetric organocatalysis discovered in the 1970s.
 20

Even more promising are the findings in a follow-up study. Here the authors report
that small peptides (mainly dipeptides tested, or peptides with no more than five
amino acids) and amino acid tetrazoles can catalyze aldol reactions, some of them
yielding sugars, with great stereospecificity in water, not just in organic solvents.

Could highly specific catalysis by amino acids or other small organic molecules
more generally, i.e. not just in this particular reaction, substitute to a certain extent
for the three-dimensional substrate pockets of catalytic polymers? Could it close
metabolic cycles?

These speculative possibilities, involving specific catalysis by organic molecules,

would come closer to the ‘metabolism-first’ scenario that was proposed by Christian
De Duve. He assumes a protometabolism involving a thioester world – providing
also energy for molecular reactions – which would have become the basis for the
emergence of the RNA world (this scenario was suggested for the ‘prebiotic soup’,
not for chemistry in hydrothermal vents). However, De Duve bases his catalysis on
multimers derived from thioesters, “structurally similar to the [first] small catalytic
proteins”. It is hard to envision how such relatively large complex catalytic units
could have constantly formed with high reproducibility in a spontaneous manner.
Such reproducibility would have been required for establishing and maintaining a
stable metabolism, or otherwise complex sequences of reactions – of course, it poses
no problem for genetic polymers, as provided by the ‘gene-first’ scenario. Yet
reproducibility (and abundance) of gene-less synthesis of putative small molecule
catalysts would likely have been a much lesser issue.

Could the unique high-pressure, high-temperature aqueous environment of deep-sea

hydrothermal vents, which produces drastic changes in the reactivity of organic
compounds (see above), also cause small organic molecules to act as specific
catalysts that would not perform this function in ‘normal’ aqueous solution?

Finally, to solve the main puzzle of the ‘gene-first’ model: could catalysis by small
organic molecules even be involved in synthesis of nucleotides and oligonucleotides
in the form of the right stereoisomers – a far more complex chemistry than just the
 21

synthesis of sugars – in the absence of precursor genetic/catalytic polymers? Future

research may inform us about all these issues.

It should be noted that the dependence on UV light for the described reactions of the
reductive citric acid cycle, possibly in conjunction with a requirement for moderate
temperatures under which these reactions were reported to proceed, would confine
this chemistry to the Earth’s surface. As Leslie Orgel points out , while historically
‘metabolism-first’ proponents mostly have argued for synthesis in deep-sea
hydrothermal vents and ‘gene-first’ proponents for a prebiotic soup on the Earth’s
surface, neither connection may be an a priori prerequisite for the respective model
– metabolism without genes could have developed on the Earth’s surface, or genes
without prior metabolism in hydrothermal vents.

On the other hand, while both these reactions of the reductive citric acid cycle and
the new synthesis of activated pyrimidine ribonucleotide monomers are reported to
require UV light, reactions seemingly confined to one location may be shown, as
knowledge advances, to also proceed in other locations under different conditions.
Synthesis of RNA monomers in hydrothermal systems could be an attractive
scenario since, as discussed above, hydrothermal pores would allow for great
accumulation of RNA monomers and oligomers by thermal gradients across them

A primordial protoplasmic globule:

So the calculation goes that the probability of forming a given 300 amino acid long
protein (say an enzyme like carboxypeptidase) randomly is (1/20)300 or 1 chance in
2.04 x 10390, which is astoundingly, mind-beggaringly improbable. This is then
cranked up by adding on the probabilities of generating 400 or so similar enzymes
until a figure is reached that is so huge that merely contemplating it causes your
brain to dribble out your ears. This gives the impression that the formation of even
the smallest organism seems totally impossible. However, this is completely
incorrect.
Firstly, the formation of biological polymers from monomers is a function of the
laws of chemistry and biochemistry, and these are decidedly not random.
 22

Secondly, the entire premise is incorrect to start off with, because in modern
abiogenesis theories the first "living things" would be much simpler, not even a
protobacteria, or a preprotobacteria (what Oparin called a protobiont and Woese
calls a progenote ), but one or more simple molecules probably not more than 30-40
subunits long. These simple molecules then slowly evolved into more cooperative
self-replicating systems, then finally into simple organisms. An illustration
comparing a hypothetical protobiont and a modern bacteria is given below.

The first "living things" could have been a single self-replicating molecule, similar
to the "self-replicating" peptide from the Ghadiri group, or the self-replicating
hexanucleotide, or possibly an RNA polymerase that acts on itself.
 23

Another view is the first self-replicators were groups of catalysts, either protein
enzymes or RNA ribozymes, that regenerated themselves as a catalytic cycle . An
example is the SunY three subunit self-replicator. These catalytic cycles could be
limited in a small pond or lagoon, or be a catalytic complex adsorbed to either clay
or lipid material on clay. Given that there are many catalytic sequences in a group
of random peptides or polynucleotides it's not unlikely that a small catalytic complex
could be formed.

These two models are not mutually exclusive. The Ghadiri peptide can mutate and
form catalytic cycles.

No matter whether the first self-replicators were single molecules, or complexes of

small molecules, this model is nothing like Hoyle's "tornado in a junkyard making a
747". Just to hammer this home, here is a simple comparison of the theory criticised
by creationists, and the actual theory of abiogenesis.
 24

Note that the real theory has a number of small steps, and in fact I've left out some
steps (especially between the hypercycle-protobiont stage) for simplicity. Each step
is associated with a small increase in organisation and complexity, and the chemicals
slowly climb towards organism-hood, rather than making one big leap.
Where the creationist idea that modern organisms form spontaneously comes from
is not certain. The first modern abiogenesis formulation, the Oparin/Haldane
hypothesis from the 20's, starts with simple proteins/proteinoids developing slowly
into cells. Even the ideas circulating in the 1850's were not "spontaneous" theories.
The nearest I can come to is Lamarck's original ideas from 1803!
Given that the creationists are criticising a theory over 150 years out of date, and
held by no modern evolutionary biologist, why go further? Because there are some
fundamental problems in statistics and biochemistry that turn up in these mistaken
"refutations".
 25

Conclusion:
Abiogenesis is the idea of how life began. Although there are plenty of hypotheses
concerning this topic, none of them is yet to be proven conclusive. Scientists are still
figuring out the answer on the origin of life. A scientific conclusion must be based
on evidence.

As science enthusiasts, we shouldn’t jump to conclusion without evidence. Just

because we haven’t found the answer, it doesn’t mean that we have to make one so
that we can comfort ourselves.

Reference:
https://medium.com/@faizzulkifly/abiogenesis-on-the-origin-of-life-
4235896baa09
The Origin of Life
"Controversies on the origin of life"
"A Strategy for Origins of Life Research"
The Fifth Miracle, Search for the origin and meaning of life.
https://www.trueorigin.org/abio.php
http://www.talkorigins.org/faqs/abioprob/
http://www.talkorigins.org/faqs/abioprob/abioprob.html
"Building Blocks of Life's Building Blocks Come From Starlight"
"Life's Building Blocks May Have Formed in Dust Around Young Sun"
"Photochemical Formation of Self–sustaining Coacervates"