RNA WORLD
– THE ORIGIN OF LIFE ON EARTH
Piotr Mucha, PhD
Faculty of Chemistry
University of Gdańsk
Poland
Course book prepared as part of the project: „Kształcimy najlepszych kompleksowy program rozwoju
doktorantów, młodych doktorów oraz akademickiej kadry dydaktycznej Uniwersytetu Gdańskiego”
Project no: UDA-POKL.04.01.01-00-017/10-00
Intercollegiate Faculty of Biotechnology UG & MUG
Gdańsk 2012
Table of contents
1. INTRODUCTION ............................................................................................................................................ 5
2. THE BEGINNING OF THE UNIVERSE .............................................................................................................. 6
3. SOLAR SYSTEM AND EARTH FORMATION ...................................................................................................10
4. PREBIOTIC EARTH........................................................................................................................................14
4.1. PREBIOTIC ATMOSPHERE ................................................................................................................................... 15
5. CHEMICAL EVOLUTION –PREBIOTIC SYNTHESIS ..........................................................................................16
5.1. OPARIN-HALDANE HYPOTHESIS .......................................................................................................................... 17
5.2. MILLER-UREY EXPERIMENT ............................................................................................................................... 18
5.3. ABIOTIC SYNTHESIS OF NUCLEOBASES .................................................................................................................. 20
5.4. ABIOTIC SYNTHESIS OF CARBOHYDRATES .............................................................................................................. 21
5.5. NUCLEOSIDE SYNTHESIS .................................................................................................................................... 23
6. THE PHENOMENON OF LIFE ........................................................................................................................25
7. RNA WORLD ................................................................................................................................................26
7.1. RNA STRUCTURE............................................................................................................................................. 27
7.2. PREBIOTIC SYNTHESIS OF RNA ........................................................................................................................... 28
7.3. RIBOZYMES THE KEY TO THE RNA WORLD ............................................................................................................ 29
7.4. RNA SELF-REPLICATION .................................................................................................................................... 30
7.5. HYPOTHETICAL FIRST RNA-BASED ORGANISM ....................................................................................................... 34
7.6. RNA WORLD RELICTS ....................................................................................................................................... 35
8. LITERATURE ................................................................................................................................................37
RNA World – The Origin of Life on Earth
by Piotr Mucha
3
1. Introduction
How did life begin on the Earth? The origin of life remains one of humankind’s great
unanswered questions, as well as one of the most experimentally challenging research areas. People
have speculated about the origin of life for ages, but until recently no convincing scientific
explanation of the problem has been proposed. The phenomenon of life is driven by the general laws
of physics and chemistry. By applying these laws over the past sixty years, spectacular progress has
been made in understanding the molecular mechanisms that are the foundations of the creation of
life.
Numerous hypotheses how life on the Earth could have started have been proposed. The
most accepted one is called the “RNA world”. It explains with the highest probability (according to
our modern knowledge) what might have caused the rise of life on the primordial Earth from a
chemical point of view. The RNA world hypothesis states that life originated via a system based on
RNA genomes and RNA catalysts.
Rediscovering the past always has been a challenging task. It is difficult to reconstruct the
primordial conditions and events that were present on the Earth 4,5-4 billion (109) years ago.
Because of geological activity, high temperature, radioactivity and harsh weather conditions all or
most of the direct evidence connected with the creation of life on Earth have been destroyed or have
at least undergone strong metamorphosis. This is the reason that our knowledge about the exact
conditions at the time during the emergence of life on Earth is foggy.
Searching for the beginning of life on the Earth is like solving puzzles in order to discover the
possible pathways through which organic molecules serving as building blocks could have been
formed in the prebiotic environment, how they might have interacted with each other, and how this
might have led to more complex structures and finally to the living cells and organisms.
Modern cell-based life is extremely complex. It is hard to imagine that even the simplest
living system could have evolved spontaneously. However, the force of nature is tremendous and
hence the phenomenon of life arose on Earth. It seems possible that nature needs some organic
matter, a universal solvent like water, a source of energy and a “little” time to create living systems.
Evolution went a long way, starting from inorganic matter through very simple organic molecules
that formed larger and more complicated molecules, which then started to interact with other
classes of molecules in the environment. As soon as membrane-like structures capable of forming
closed spheres appeared in the environment, fragile molecules and polymers that would otherwise
hydrolyze or not even form at all in the harsh primordial environment had the opportunity to
participate in chemical evolution inside these cell-like structures in a safe surrounding. Searching for
the sources of life on the Earth is one of the most challenging and complicated tasks humankind has
ever undertaken. However, a few steps in the right direction have been made.
RNA World – The Origin of Life on Earth
by Piotr Mucha
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2. The beginning of the Universe
One of the most persistently asked questions preceding the problem of the creation of life is
how was the universe created? Till recently it was believed that the universe had no beginning or end
and was truly infinite. Astronomical observations as well as theoretical works delivered data that this
idea was completely wrong and the universe possesses a beginning, history and a future. The best
commonly accepted theory of the creation of the universe is called the Big Bang. The Big Bang theory
provides a viable solution to one of the most pressing questions as to how the universe and
everything within was born.
About 13,7 billion years ago a tremendous “explosion” started the expansion of the universe
[1-3]. The “explosion” is known as the Big Bang. At the point of this event all of the matter and
energy of space was contained at one point of infinity, density and temperature. This occurrence was
not a “conventional explosion” but rather an event creating time and space and events within.
There was a time, not long ago, when scientists were fighting over whether the Big Bang was
the correct model for the universe, or something else like the steady state theory, or perhaps some
variation on an oscillating universe was more probable. The foundations of the Big Bang theory can
be credited to the astronomer Edwin Hubble. Hubble’s observations made in the 1920s, showed that
our galaxy - the Milky Way was one of many, and that these galaxies escaped from each other with a
velocity proportional to their distance [3]. This phenomenon of galaxies moving farther away from
each other is known as the red shift. A consequence of this observation was the conclusion that the
universe was continuously expanding in every direction and it had a beginning (Fig. 1).
Fig. 1. Model of the expanding universe. Almost all galaxies escape from each other.
Upper subset figure shows a wavelength red shift mechanism
[source: http://scienceblogs.com/startswithabang/2010/04/05/did-the-universe-start-from-a/]
In addition to the understanding of the velocity of galaxies emanating from a single point,
there is further evidence for the Big Bang. Even before Hubble’s discovery, Albert Einstein in 1917,
showed in his gravitational field equations, that the universe was expanding. However, Einstein
believed in a static (stationary), eternal and invariable universe. So, he modified (by removing an
element responsible for repulsion of matter) his equation to fit what he believed.
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RNA World – The Origin of Life on Earth
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In 1964 one of the biggest discoveries in the history of mankind’s understanding of the
universe was made. Arno Penzias and Robert Wilson discovered an echo of the Big Bang-the
beginning of the Universe [4]. In an attempt to detect microwaves from outer space they
inadvertently and persistently heard a noise of outer space origin. The noise did not seem to
emanate from one particular location but instead, it came from all directions at once with the same
intensity. They heard “a sound” (microwaves are of radio-range wavelengths) that was reminiscent
from the farthest reaches of the universe which had been left over from the Big Bang. The radiation
was called cosmic microwaves background (CMB) or relic radiation and was the strongest direct
evidence of the Big Bang. Because of the universe expanding and cooling down the relic radiation is
of about 2,7 K which reflect microwave wavelength range [1, 2]. CMB is also called the last scattering
(“visible”) surface and is a firm limit to the direct observation of the universe.
Modern data from WMAP and COBE satellites showed that the relic radiation was
remarkably uniform which confirmed high level of homogeneity of the newly-born universe (Fig. 2).
Fig. 2. Cosmic microwaves background (CMB). WMAP’s view of the universe from the first seven years of data.
The tiny hot spots (marked in yellow and red) in CMB are primordial lumps of matter that ultimately grew
into the stars and galaxies visible today [source: NASA/WMAP Science Team]
However, satellites also discovered that just after the beginning of the universe during its fast
expanding, small fluctuations appeared due to temperature differences (at a sensitivity range of 10-4
K) [1]. These fluctuations confirm the theoretical predictions which stated that such anomalies were
necessary to initiate clustering of matter and formation of galaxies. These fluctuations of CMB in the
young universe provided a more detailed description of the first moments after the Big Bang than
ever could have been investigated experimentally.
Immediately after the Big Bang, the universe was tremendously hot. As it began to cool, at
around 10-38 seconds after creation, almost an equal amount of matter and antimatter existed (Fig. 3)
[1, 2].
RNA World – The Origin of Life on Earth
by Piotr Mucha
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A)
B)
Fig. 3. The main events after the Big Bang (A) and expanding universe
[source: A) www.mahjoob.com/en/forums/showthread.php?t=275459, B) NASA/WMAP Science Team]
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RNA World – The Origin of Life on Earth
by Piotr Mucha
As these two types of matter were created together, they destroyed one another creating
pure energy (gamma ray photons). Fortunately, there was a small predominance of “normal” matter.
As a direct result of an excess of about one particle per billion of “normal” matter over antimatter,
the universe was able to exist as we know it now. However, modern data show that “normal matter”
constitutes only of 4-5% of “substance” of which the universe is composed (Fig. 4) [1].
Fig. 4. Composition of the universe [source: http://map.gsfc.nasa.gov/universe/uni_matter.html]
The composition of the main constituents called dark energy and matter is unknown. As the
universe was expanding and cooling down, matter started to dominate over radiation. At the
extremely high temperature at the beginning of the universe only exotic particles, in comparison to
presently known particles of matter, existed. At this moment, there was only a quark soup [1]. As the
universe expanded and cooled further, “common” particles began to form. These particles are called
baryons (including quarks, photons, neutrinos, electrons) and would become the building blocks of
matter and life as we know it. During the baryon genesis era there were no heavy particles such as
protons or neutrons because of the temperature being too high. As the universe began to cool and
expand even more, we begin to understand more clearly what exactly happened. After the universe
had cooled to about 1013 K, heavy particles such as protons (p) and neutrons (n), called hadrons,
appeared and became the common state of matter [1, 2]. Still, no matter more complex that these
nucleons could form at these temperatures. Although lighter particles, called leptons including
electrons, neutrinos and photons, also existed, they were not capable of binding with the hadrons to
form atoms. These leptons would soon be able to join their hadron partners to form “normal” matter
as we know it now. After about one to three minutes had passed since the Big Bang, protons and
neutrons began to react with each other to form deuterium nucleus (1p+1n), a heavy isotope of
hydrogen (Fig. 5).
Fig. 5. Nucleosynthesis during the first minutes of the universe
RNA World – The Origin of Life on Earth
by Piotr Mucha
9
Deuterium, soon collected another neutron to form tritium (1p+2n), the heaviest and the
most unstable isotope of hydrogen. Rapidly following this reaction, the addition of another proton
which produced a helium nucleus occurred. There was one helium nucleus for every ten protons
within the first three minutes of the universe. After further cooling, these excess protons would be
able to capture an electron to create “common” hydrogen atoms. In consequence of these nuclear
reactions of the young universe, the modern universe contains one helium atom for every ten or
eleven atoms of hydrogen [1]. This gives a composition of the universe stated as hydrogen:helium 9:1
(by atom number).
3. Solar System and Earth formation
To understand the beginning of life it is necessary to look at the conditions of the prebiotic
Earth. As the universe was expanding and simultaneously cooling down, large volumes of matter
collapsed under a gravitational influence to form galaxies. Gravitational attraction pulled galaxies
towards each other to form a hierarchical structure of the universe: groups, clusters and
superclusters [2]. Since the expansion of the universe accelerates, superclusters are the largest
structures that will ever form in the universe. Among the billions of galaxies, there is one where we
were born and live - our galaxy called the Milky Way (Fig. 5).
Fig. 5. Milky Way (spiral)-type galaxy [source: www.windows2universe.org]
Milky Way belongs to a local group of galaxies in the Virgo supercluster (Fig. 6). Its spiral disk
is estimated to have been formed around 9 billion years ago.
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RNA World – The Origin of Life on Earth
by Piotr Mucha
Fig. 6. Local group of the Milky Way galaxy. [source: www.atlasoftheuniverse.com/localgr.html]
Our solar system is located at the periphery of the galactic disc (Fig. 7). The age of the solar
system and the Earth has been determined to be approximately 4.6 billion years old (formed over 9
billion years ago after the Bing Bang).
Fig. 7. Location of the sun (and the solar system) in the Milky Way galaxy
[source: www.danielsevo.com/astronomy/astro_galaxy.htm]
The solar system is thought to have formed by the coalescence of a nebular cloud (Fig. 8).
After the initial phase of the solar system formation, a cloud of gas, dust, and ice-covered dust
formed [2, 5]. The gas was made primarily of hydrogen and helium, the dust was made of heavier
elements and materials (silicates, iron, carbon), and the ice was composed of water, methane (CH 4 ),
and ammonia (NH 3 ).
RNA World – The Origin of Life on Earth
by Piotr Mucha
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Fig. 8. A scheme of the solar system creation. The cloud shrinks and
it starts to spin faster (A). As this happens, the centrifugal force
causes it to flatten into a disk-like shape (B). The gas makes up the
bulk of the disk. As the density and temperature grow, at the central
region of the solar nebula thermonuclear reactions start and the Sun
-5
is formed (C). The solid material (the dust particles of ~10 m in size,
and the ice-covered dust) embedded in the cloud collide and
coalesce. They collide and stick together and form planetesimals (D).
The gravity of the planetesimals is large enough to start attracting
other planetesimals and form larger bodies referred to as
protoplanets (E). Finally the planets are formed in the disk. [Source:
www.kirksville.k12.mo.us/khs/teacher_web/alternative
/universe.html
At this time the solar system was filled with hot gases (mainly hydrogen and much less
helium) and dust enriched in heavier elements produced in exploding supernovae, which swirled and
revolved around a hot center collapsing gravitationally on itself. The cloud condensed, became more
disk-like, and began to rotate. Once the center of the disk achieved a temperature of 106 K and
pressure high enough to begin hydrogen fusion, the sun was born [1, 2]. The sun is a late (second or
third)-generation star, composed mainly of hydrogen and helium and containing small heavier
ingredients from earlier stars. The intense radiation of the newly-born sun drove the lower boiling
point elements outward toward the edge of the solar system where they condensed and froze out.
Farther out in the disk, dust-sized particles were also in the process of coalescing due to gravitational
attraction. The gaseous-dust cloud slowly condensed and formed small solid particles. They attracted
each other creating bigger forms-asteroids. Asteroids collided with each other forming bigger
structures, about 1 km in diameter, called planetesimals (Fig. 9) [2, 5].
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RNA World – The Origin of Life on Earth
by Piotr Mucha
Fig. 9. Planetismals started formation of planets
They were the “germs” of planet formation. Many planetesimals collided with each other.
While some of these collisions destroyed them, others caused them to aggregate and grow. As their
mass increased, gravity pulled in more particles, and the planetesimals grew larger, forming
protoplanets and finally planets [5]. This process is called accretion and explains how the Earth and
the other planets of the Solar system were formed (Fig. 10).
Fig. 10. Planets of the solar system. Neptune (not shown) has been “degraded” and now is classified
as an object of the Kuiper Belt or dwarfed planet
[source: www.phys.org/news/2011-02-marstinis-red-planet-small.html]
It seems to be a general scenario of forming any planetary system in a galaxy. The Earth’s
natural satellite, the Moon is thought to have formed from the collision of a Mars-sized body with
the primitive Earth about 4.5 billion years ago [1, 2]. The kinetic energy of such a large collision must
have been enormous and it would have provided enough energy to entirely melt the newly formed
Earth and probably strip away its original atmosphere composed mainly of hydrogen and helium.
RNA World – The Origin of Life on Earth
by Piotr Mucha
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4. Prebiotic Earth
When the Earth was formed, it was a very hot and hostile planet due to heavy bombardment
by meteors and asteroids during the first hundred million years. These asteroids released such an
enormous amount of energy upon impact that the earth's barely solidifying crust began to melt
[2, 6]. Radioactivity-originated heat from the earth's core also strongly influenced the melting. All
these events released enormous amounts of gases from the earth's interior. The first hundred million
years were characterized by severe melting and remelting of the rocks on the surface of the planet.
After this process slowed, a solid crust began to form. However, the continued bombardment kept
on tearing up its face for another several hundred million years. As the Earth cooled down enough to
form a thin layer of crust, volcanic activity strongly influenced the newly-born Earth’s surface
(Fig. 11).
Fig. 11. Artistic views of the prebiotic Earth environment.
Most of the surface was melted and volcanic activity and lava lakes dominated
[source: www.mahjoob.com/en/forums/showthread.php?t=275459]
Enormous amounts of heat and kinetic energy caused by asteroid impacts and radioactivity
decay from the interior of the planet, caused volcanoes to spew forth lava, as well as various gases
which had been trapped under the surface (Fig. 11). As the lava covered the Earth the earliest
evidences of planet formation were erased forever. Around 4 billion years ago, the bombardment of
the Earth stopped, the temperature dropped much below the boiling point of water and the stable
hydrosphere,oceans and lakes, could form (Fig. 12) [5, 6].
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RNA World – The Origin of Life on Earth
by Piotr Mucha
Fig. 12. Calendar of events on the Earth
4.1. Prebiotic atmosphere
Physicochemical properties of the primordial atmosphere of the Earth is of crucial
importance for creating building blocks for organic molecules and in consequence for living systems.
However, its composition is still an open and wildly disputable question. One thing seems to be
certain, the lightest gases like hydrogen and helium would have rapidly escaped (into outer space)
the weak gravitational field of a medium-size planet like the Earth [1, 2]. This process was highly
accelerated by the impact of high temperature of the planet and meteorites. A significant amount of
water was being released from the melted rocks below the crust and became the main component of
the secondary atmosphere of the prebiotic Earth [2, 5].
As the planet continued to be bombarded from outer space, water released from asteroids
and from its interior (a process referred to as "outgassing") rose into the atmosphere and together
with carbon dioxide, nitrogen and other gases, formed incredibly dense clouds (Fig. 12.1). These
clouds formed a reflective shield above the Earth, keeping solar radiation from penetrating to the
surface (Fig. 12.2).
As the frequency of meteorite impacts declined, the surface of the earth began to cool.
When this happened, the immense clouds which had emerged began to pour rain over the entire
planet, cooling the molten rock, and creating oceans (Fig. 12.3). Water of outer space and of under
the crust origin was a crucial requirement for the formation of life.
RNA World – The Origin of Life on Earth
by Piotr Mucha
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Fig. 12. Formation of the stable hydrosphere (oceans and lakes) on the primordial Earth
For a long time it was thought that the early Earth had a reductive atmosphere [5, 7]. A
reducing atmosphere contains reductants, or molecules saturated with hydrogen atoms, which are
able to reduce other molecules. Many scientists thought that the primordial atmosphere consisted of
methane, ammonia and hydrogen [5, 8]. This is the mixture of gases Miller used in 1953 to mimic the
prebiotic conditions of the early Earth. However, taking clues from Earth's neighboring planets Venus
and Mars, one might expect high concentrations of carbon dioxide (CO 2 ), with small amounts of
methane, ammonia and hydrogen. Nitrogen probably also was present [1, 5]. However, hydrogen has
a tendency to leave the planet. Analysis of the oldest rocks on Earth found at Greenland seems to
confirm, that the primordial atmosphere was rather slightly reductive or neutral.
5. Chemical evolution –prebiotic synthesis
The Wöhler’s synthesis of urea in 1828 is of great historical significance because for the first
time an organic compound was obtained from inorganic substrates [9]. One of the simplest organic
molecules - urea was discovered much earlier in 1799 and could until then only be obtained from
biological sources such as urine. For this reason a sharp border existed between organic and
inorganic matter. Although it was not immediately recognized as such, a new era in chemical
research had begun. The Wöhler’s discovery is considered the starting point of modern organic
chemistry. Wohler discovered that after heating an inorganic substance, ammonium isocyanate, it
had rearranged to form “bioorganic” urea (Fig. 13).
NH 4 NCO → (H 2 N )2 CO
Fig. 13. Wohler’s synthesis of urea
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RNA World – The Origin of Life on Earth
by Piotr Mucha
This finding went against the mainstream theory of that time called vitalism which stated
that organic matter was endowed with a special force called vis vitalis inherent to all living things.
Wohler’s discovery buried the vitalism theory and showed that there was nothing special in organic
matter.
5.1. Oparin-Haldane hypothesis
There had been a long tradition of belief, dating back to Aristotle, in the spontaneous
generation of life. However, in 1862, Louis Pasteur published results which conclusively refuted the
theory of spontaneous generation of life under the ‘vis vitalis’ force. After his discovery, the
discussion of the origins of life has been a subject of scientific rather than useless speculations.
In the twenties of the 20th century, Aleksandr Oparin and John Haldane published one of the
most famous hypothesis of the origins of life [6, 8]. This idea is known as the theory of prebiotic
evolution or “primordial soup”. One of the reasons that the Oparin-Haldane theory was unique and
valuable, was that as a hypothesis, it could be proved wrong. This is not a trivial aspect in the context
of searching for the origins of life.
Oparin/Haldane assumed that if the primordial atmosphere of the Earth was reducing, and if
there was an appropriate source of energy, such as solar ultraviolet light or lightning, then a wide
range of organic compounds might be synthesized [6]. Prebiotic evolution holds that life originated
gradually from interaction between different inorganic and organic matter in the prebiotic Earth's
atmosphere and that matter has a tendency for self-organization which finally guides itself to the
formation of living systems. According to the Oparin-Haldane hypothesis, upon the Earth’s formation
the atmosphere was composed of four gases: hydrogen, water vapor, ammonia and methane. These
compounds would have reacted spontaneously and during these reactions the first organic (more
complicated than methane) compounds were synthesized in an abiotic way. The energy required for
these reactions came from the highly unstable environment of the prebiotic Earth, mostly from
ultraviolet solar radiation and electrical discharges from lightings as well as from volcanoe eruptions
[8].
After synthesis in the prebiotic atmosphere, the first compounds would have been
translocated by rain and accumulated into water reservoirs (oceans and lakes). Due to their high
concentration, molecules would react with each other creating more complex and higher organized
structures. These molecules in the aqueous environment formed an organic "primordial soup"
(Fig. 14).
Through this chemical evolution all building blocks composed of organic molecules necessary
for the emergence of life came to be. Further, organic molecules clustered spontaneously in small
groups isolated through a semipermeable lipid-composed membrane (which enabled the exchange
of molecules with the environment) resulting in the formation of probionts, prebiological living-like
forms [6, 7]. Inside these forms (bubbles) chemical reactions fundamental to life would have taken
place. The prebiological forms then would have originated more and more complex forms that would
have created truly living RNA-based forms and finally modern DNA-based organisms.
RNA World – The Origin of Life on Earth
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Fig. 14. Oparin-Haldane theory
5.2. Miller-Urey experiment
The Oparin-Haldane theory of prebiotic chemical evolution was an important step on the
road to illuminate the origins of life. What’s important it could be verified experimentally. Very few
chemical experiments resulted in as much publicity as the first synthesis of organic molecules under
prebiotic conditions carried out by Stanley Miller more than 50 years ago [10]. This experiment is
probably as well known as the Wohler’s synthesis of urea. To build any living system organic
molecules are necessary. Thus, the main point of the Miller- Urey experiment was to give an answer
how to set, under the appropriate conditions of the early atmosphere, prebiotic organic building
blocks of the first living system from the simplest inorganic and organic compounds. The Miller-Urey
experiment showed that abiotic molecules could be used to create important biotic compounds
thought to be necessary for the origins of life. This was the first experiment that laid the foundation
for the Oparin-Haldane's theory. Miller and Urey simulated the hypothetical prebiotic reducing
primeval Earth atmosphere conditions in the laboratory [6, 10]. They provided the early atmosphere
gases: methane, hydrogen, ammonia, water vapor, and provided the system with enough energy to
make synthetic reactions possible by subjecting it to electrical discharges (Fig. 15).
Later, upon condensation water changed color and a tar-like substance formed in the flask.
After a week, 10-15% of methane was present in the form of organic materials [7, 8]. Apart from
a few simple organic molecules, Miller was able to detect the presence of at least 15 amino acids,
in particular glycine and alanine, the building blocks of proteins (Table 1).
18
RNA World – The Origin of Life on Earth
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Fig. 15. Apparatuses of Miller’s experiment
[source: www.uic.edu/classes/bios/bios104/mike/thedynamicearth.htm]
a
Table 1. Products of Miller-Urey experiment. proteinogenic amino acid [6, 8]
Compound
a
Glycine
Glycolic acid
Sarcosine
a
Alanine
Lactic acid
N-Methylalanine
α-Amino-n-butyric acid
α-Aminoisobutyric acid
α-Hydroxybutyric acid
β-Alanine
Succinic acid
a
Aspartic acid
a
Glutamic acid
Iminodiacetic acid
Iminoaceticpropionic acid
Formic acid
Acetic acid
Propionic acid
Urea
N-Methylurea
Yield (%)
2.1
1.9
0.25
1.7
1.6
0.07
0.34
0.007
0.34
0.76
0.27
0.024
0.051
0.37
0.13
4.0
0.51
0.66
0.034
0.051
About 2% of methane was in the form of amino acids. His experiment provided the first proof
that the question of the origins of life is a scientific problem which can be approached by scientific
methodology.
RNA World – The Origin of Life on Earth
by Piotr Mucha
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5.3. Abiotic synthesis of nucleobases
If the RNA world preceded more complex DNA-based forms of life, then the first nucleotidesbuilding blocks of nucleic acids were synthesized before RNA molecules. There were no enzymes to
facilitate the synthesis of the first nucleotides so another way of chemical evolution must have been
involved. Substantial progress has been made in the synthesis of nucleobases, sacharides (including
ribose), nucleosides and its phosphorylated analogues-nucleotides. [7, 11, 12]. The outstanding
problems relate to the synthesis of ribose to the exclusion of the other aldopentoses and to the
problem of linking ribose to the purine bases [7, 11].
A few years after the Miller experiment was published, another important biomolecule purine nucleobase called adenine was synthesized. It has been shown that heating ammonium
cyanide for a few days led to adenine synthesis [6, 7]. The same effect was obtained by a
polymerization of hydrogen cyanide (HCN) that gives the same product (Fig. 16).
Fig. 16. Prebiotic synthesis of purine nucleobases [7]
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RNA World – The Origin of Life on Earth
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It is known that hydrocyanic acid molecules are found in interstellar space. The question thus
arises as to whether there is a connection between the immense importance of adenine in living cells
and the occurrence in outer space of a building block for its formation.
The route to the synthesis of pyrimidine nucleobases - cytosine and uracil has also been
found. Starting from cyanoacetylene (a simple derivative of HCN) and urea, cytosine was synthesized
(Fig. 17) [6-8]. Thus after its hydrolysis uracil was obtained.
Fig. 17. Prebiotic synthesis of pirymidine nucleobasess [8]
5.4. Abiotic synthesis of carbohydrates
Carbohydrates (especially ribose being a component of nucleic acids) are still difficult to
synthesize “rationally” using prebiotic chemistry. Although the first synthesis of carbohydrates
by Butlerov were described more than 150 years ago, their prebiotic synthesis is still challenging.
The simplest way is through heating a formaldehyde solution under alkaline conditions that easily
leads to a sugar mixture (Fig. 18) [6-8].
This is called a formose reaction, a complicated autocatalytic process that requires inorganic
catalysts such as calcium hydroxide or carbonate. A number of intermediates are formed:
glycolaldehyde, glycerine aldehyde, dihydroxyacetone, carbohydrates: tetroses, pentoses and
hexoses. This “prebiotic syntheses” utilizes catalytically active clays such as kaolin in order to obtain
sugars. The “most important” carbohydrate-ribose is also formed, although in only small amounts.
Although the formose reaction is readily carried out even at prebiotic conditions, it generates various
problems. In the course of the reaction almost 40 different carbohydrates are formed. Those
required for nucleic acid synthesis, ribose and deoxyribose, are obtained in extremely low yields of
less than 1% [6, 8]. It is questionable whether these could have been separated from the others
under primeval Earth conditions. Ribose is relatively unstable in an aqueous solution especially at
high temperatures and in a basic (pH>8) environment [11]. These facts require that ribose must have
undergone further reactions immediately after its formation under prebiotic conditions. Ribose and
other pentoses are made under alkaline conditions from simple organic precursors (glycolaldehyde
(1) and formaldehyde (2)) known to be present in the interstellar space and presumably available on
the prebiotic Earth (Fig. 19) [13].
RNA World – The Origin of Life on Earth
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21
Fig. 18. Formose reaction [8]
Fig. 19. Prebiotic synthesis of ribose in the presence of borate [13]
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RNA World – The Origin of Life on Earth
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Ribose does not accumulate under these conditions (without stabilizers). The obtained
carbohydrates rapidly decompose in a “browning” reaction to generate largely undefined polymeric
mixtures. It is known that inorganic minerals may catalyze various chemical reactions and may
stabilize their products. Because borate minerals form complexes with organic molecules (such as
pentoses) that carry geminal (neighboring) dihydroxyl groups, ribose might accumulate to reach a
high concentration if borate were present [13].
This data shows that the formation of pentoses including ribose, appears to be the natural
outcome of the chemical transformation of simple organic molecules present on the prebiotic Earth
in the presence of easily accessible inorganic (borate) minerals. Such types of reactions could be a
source of ribose for prebiotic synthesis of nucleosides and ancient nucleic acids. Of course, it is
possible that other more stable carbohydrates were used to build ancient nucleic acids or they did
not contain sugars at all (like peptide nucleic acids, PNA).
5.5. Nucleoside synthesis
The synthesis of nucleosides from ribose and nucleobases are the weakest link in the chain of
prebiotic reactions leading finally to oligonucleotides (RNA) [8]. Even if ribose is obtained using the
method presented in Fig. 19, it is very difficult to ligate this carbohydrate to a nucleobase directly to
form a nucleotide especially under prebiotic conditions (Fig. 20).
Fig. 20. “Uphill” synthesis of nucleoside
If ribose is heated with hypoxanthine (not present in modern nucleic acids) in the presence of
condensing (water binding) compounds, up to a few percent of nucleosides,- inosine is formed [6, 7].
The product mixture obtained from adenine under the same conditions is more complex, since the
major reaction occurs at the amino-group of the base, and nucleoside formation is a relatively minor
side reaction. No direct synthesis of pyrimidine nucleosides from ribose and uracil or cytosine has
been reported. However, an indirect synthesis of cytidine from arabinose (converted to ribose at the
last step of the reaction), cyanamide, and cyanoacetylene in aqueous solution is possible (Fig. 21)
[14].
RNA World – The Origin of Life on Earth
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23
Fig. 21. Synthesis of cytosine arabinoside from arabinose, cyanamide, and cyanoacetylene (a). Modification of
the mode of hydrolysis of cyclocytidine caused by its 3’-phosphorylation (b) which leads to 2’,3’cyclophosphate cytidine [14]
Recently the problem of carbohydrate and nucleobase linkage has been solved. An elegant
route leading to nucleotide synthesis has been proposed (Fig. 22) [15]. The proposed route suggests
that the prebiotic synthesis of activated pyrimidine nucleotides should be viewed as predisposed.
This predisposition would have allowed the synthesis to operate on the primordial Earth.
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RNA World – The Origin of Life on Earth
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Fig. 22. An alternative route of prebiotic synthesis of the pyrimidine ribonucleotide. Previously assumed
synthesis of β-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 (green).
p, pyranose; f, furanose [15]
6. The phenomenon of life
In the process of trying to understand the origins of life it is useful to define this
phenomenon. However, defining "life" is a broad question that affects many branches of biology,
biochemistry, genetics, and informatics. There are a lot of definitions of life. Moreover, the
“biological point of view” can differ dramatically from others. NASA's definition of life "Life is a selfsustained chemical system capable of undergoing Darwinian evolution" is one of the simplest and
most useful. Some general features of life can be noticed. Living systems tend to be complex and
highly organized. This means that some energy is used to keep entropy at a low level. This energy is
taken from the environment and transformed to a useful form to sustain metabolism. Living systems
are formed of only a very limited set of chemical elements. Most of them like hydrogen, carbon,
oxygen, nitrogen and are abundant in the universe (Fig. 23) [6, 16]. Elements like sulfur, calcium,
potassium, phosphorous and some others are much less populated.
RNA World – The Origin of Life on Earth
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25
Fig. 23. Abundance of chemical elements in the universe
[source: www.schoolworkhelper.net/comparison-of-abundance-of-elements/
Life is cellular, confined and separated from its environment. However, a living system is able
to respond to external signals and can exchange some compounds bidirectionally with its
environment. A living system tends toward homeostasis: an equilibrium of parameters that define its
internal environment. It must respond and react to environmental signals. Life is reproductive, as
some kind of replication (reproduction) is needed for evolution to take hold through a population's
mutation and natural selection. Present and probably ancient life on the Earth share a carbon-based
chemistry and depend on water.
7. RNA world
One severe problem in trying to understand the possible pathway leading from simple
organic molecules to the first living cell is that in modern life one class of biomolecules is strongly
dependent on the others and vice versa. DNA carries all the information that is necessary to build up
proteins, but by itself depends on proteins that control DNA functions (including replication). This
leads to a kind of hen and egg problem: what came first? A solution for this problem is the RNA
world, an event occurring before DNA and proteins came into play. RNA is able to carry genetic
information and can also have catalytic activity. Life probably originated as a system of selfreplicating, catalytic RNA molecules. The term “RNA world” was first used in 1986 by Walter Gilbert
[17]. The RNA world hypothesis states that at some stage in the early evolution of life, RNA formed
both the genome and genome-encoded catalysts. The hypothesis explains how this interdependent
situation could have been solved in a world without DNA or proteins. The hypothesis could not be
examined in detail because there is no experimental model available. The RNA world hypothesis is
supported by its power to explain the problem of storing genetic information and its replication using
the same molecule. RNA preceded DNA, serving simultaneously as genetic material and as catalyst,
later passing on its genomic role to DNA and most (but not all) of its catalytic roles to proteins. First,
DNA replication requires proteins to catalyze and control the process, then protein synthesis requires
that the amino acid sequence be encoded in a DNA sequence.
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RNA World – The Origin of Life on Earth
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7.1. RNA structure
To understand the role of RNA as the protoplast molecule which started the chain of life on
the Earth it is necessary to learn its composition and structure. RNA is a chain polymer composed of
nucleotide residues. Nucleotides are composed of three elements: nucleobases, carbohydrate
(ribose) and phosphate residues (Fig. 24).
Fig. 24. The general structure of a ribonucleotide (A) and nucleotides present in the RNA structure (B).
The key for RNA function, the 2’-OH group is marked with red (A). Nucleoside structures are marked with pink
The unique features of the RNA molecule are correlated with the presence of a hydroxyl
group bound to C2’ carbon atom of the ribose residue (Fig. 25). The RNA chain is a polymer
composed of ribonucleoside residues connected with a 3’,5’-phosphate diester linkage (Fig. 25).
Almost all biologically active RNA molecules exist as a mixture of single and double strands.
This phenomenon leads to the unusual spectrum of special structures and functions that RNA may
adopt and carry on. RNA molecules fold to adopt one of the most complicated spatial structures ever
known among other biopolymers. The most important determinant of folding and shape in RNA is
complementary base pairing via hydrogen bonding, according to the base-pair rules first established
by Watson and Crick. This phenomenon is also responsible for transferring genetic information and
self-replication ability.
RNA World – The Origin of Life on Earth
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27
Fig. 25. Structure of the RNA chain
7.2. Prebiotic synthesis of RNA
The polymerization of nucleotides in an aqueous solution does not occur spontaneously to a
significant extent [6, 7]. Evaporation of acidic solutions of nucleotides and subsequent heating leads
to the formation of complex mixtures of very short oligonucleotides. Consequently, attempts to
polymerize nucleotides from an aqueous solution must necessarily make use of external activating
agents. Polymerization of preactivated nucleotides has been met with greater success [7, 16].
Unfortunately, nucleoside-5’-triphosphates react so slowly in an aqueous solution at moderate
temperatures and pHs that their polymerization cannot easily be studied in the laboratory. Instead,
nucleotides activated as phosphoramidates, usually phosphorimidazolides, have been used
successfully as substrates in most experiments (Fig. 26) [14].
Fig. 26. Prebiotic synthesis of RNA [14]
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RNA World – The Origin of Life on Earth
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However, it is unclear that phosphorimidazolides could have occurred in large amounts on
the prebiotic Earth, so these experiments form only a rough guide to the classes of reactions that
might have been relevant to the chemical evolution. The source of the free energy needed to drive
the uphill polymerization of nucleotides is unclear. However, successful polymerization of activated
nucleotides shows that prebiotic non enzymatic synthesis of RNA was possible even without
matrices.
7.3. Ribozymes the key to the RNA world
The chemical composition, structure and function of RNA in modern living cells has been
“known” for a long time. The “standard trinity” of RNAs: mRNA, tRNA, and rRNA filled in the blanks of
our knowledge regarding the cellular functions of RNA. However, one of the most unexpected
discoveries in the history of nucleic acid research influencing this “well established” knowledge was
to be made. In the early 1980s Thomas Cech and Sidney Altman independently discovered that RNA
has catalytic ability [17]. Before this it was thought that only proteins possessed enzymatic activity.
Cech and his group were studying the splicing of large ribosomal RNA (rRNA) precursors in the
protozoon Tetrahymena (Fig. 27).
Fig. 27. Cech’s discovery of ribozymes
They observed that the RNA precursor spontaneously changed size, becoming smaller after
incubation in a protein-free buffer solution containing only magnesium (Mg2+) ions. Cech showed
that this RNA, the “group I intron,” has the inherent ability to catalyze its own excision from the RNA
precursor. This RNA intron catalyzes its own self-splicing without the aid of any protein. Altman
investigated the activity of the Escherichia coli enzyme called RNase P (Fig. 28).
RNA World – The Origin of Life on Earth
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Fig. 28. Altman’s discovery of ribozymes
The enzyme was composed of protein and RNA components and trimmed the 5’-end of a
transfer RNA precursor (pre-tRNA). The conventional prejudice was that the protein must act as an
“enzyme.” But any effort to remove the RNA component eliminated its catalytic ability. Altman
showed that the RNA component of RNase P itself was sufficient to catalyze the trimming reaction.
The RNA, in this case, was a catalyst acting not on itself but on another RNA.
The discovery of ribozymes clearly was the catalyst for the current intense interest in the
RNA world hypothesis. But the idea that RNA perhaps was the first genetic molecule is not new.
Francis Crick and Leslie Orgel first proposed the possibility in 1968 [17]. However, without knowing
the catalytic activities of RNA their proposal was a pure speculation.
7.4. RNA self-replication
Just after the discovery of catalytic RNAs by Altman and Cech, attempts to recreate the RNA
world in the laboratory started. A molecular system to be called ‘alive’ must self-replicate, generate
stochastic variations and have the potential to increase in complexity through evolution. Selfreplicating ribozyme systems that replicate through polymerization would fulfill all these
requirements (Fig. 29) [14, 17].
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RNA World – The Origin of Life on Earth
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Fig. 29. A scheme of a self-replication of ribozyme through a matrix (complementary strand) (A)
and in a mixed model (with and without matrix) (B) (tem-with template, untem-without template) [14]
The creation of a life-like system similar to the early stages of the evolution of life would
enable to learn about the origin of life. The simple, fully self-replicating and evolving system might
illuminate fundamental biophysical and biochemical laws that are currently hidden from view by the
complexity of modern life forms. RNA’s informational, template, and catalytic abilities led to the
assumption that RNA evolved, before the appearance of DNA or protein, in the RNA world. RNA is
assumed to have provided both the coding and the catalytic abilities necessary and sufficient to
initiate a chain of life and biological evolution on the Earth. One could say that the RNA molecule was
a “biblical first world” that started life on the Earth.
Catalytic abilities of the first RNA molecules were necessary but insufficient to create the first
living system. However, if ancient RNA’s catalytic abilities extended to its own self-replication, then
RNA World – The Origin of Life on Earth
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the phenomenon of life and evolution would have started as randomly variant RNAs were naturally
selected on the basis of evermore efficient replication ability. The ability for self - replication, the
foundation of the RNA world hypothesis, remains to be demonstrated. It is the “Holy Grail” of the
RNA world. No RNA sequence possessing self – replication (RNA replicase) activity has yet been
found in nature, but some steps toward creating and designing a self-replicator RNA molecule in vitro
have been taken. Even though no RNA capable of catalyzing its own replication has yet been found in
nature, some experiments in in vitro selection (SELEX) have demonstrated that RNA indeed has such
potential (Table 2) [18]. The goal of such experiments is to create and amplify those variants of RNA
that are able to meet some experimentally imposed selection criterion, such as the ability to undergo
polymerization, ligation or replication.
Table 2. Examples of new ribozymes from random-sequence RNA selections [18]
Bond formed
-O–PO 3 HO–PO 3 -O–PO 3 -O–PO 3 -O–PO 3 -O–PO 3 -O–PO 3 -O–PO 3 -O–PO 3 <
-O–CO-O–CO-O–CO-HN–CO-HN–CO>N–CH 2 -S–CH 2 >HC–CH<
>N–CH<
Leaving group
5′-RNA
PP
PP
AMP
ADP
Imidizole
Rpp
PP
AMP
3′-RNA
AMP
3′-RNA
AMP
I
Br
PP
Activity of ribozyme
Phosphodiester cleavage
Cyclic phosphate hydrolysis
RNA ligation
Limited polymerization
RNA ligation
RNA phosphorylation
Tetraphosphate cap formation
Phosphate anhydride transfer
RNA branch formation
RNA aminoacylation
Acyl transfer
Acyl transfer
Amide bond formation
Peptide bond formation
RNA alkylation
Thio alkylation
Diels–Alder addition
Glycosidic bond formation
Although no fully self-replicable RNA molecule has yet been discovered, many constructed
ribozymes displayed properties useful for creating the first RNA-based living system (Fig. 30) [19].
Some of these synthetic RNAs can copy an RNA template, forming short complementary
strands. Further laboratory refinements of this molecule may yield a bona fide RNA-dependent RNA
polymerase, a key ribozyme activity required for self-replication.
Just as the replicase property of RNA would have marked the beginning of the RNA world,
the emergence of coded protein synthesis would herald the beginning of the protein–nucleic-acid
world [17, 19]. The fact that RNA can catalyse the chemistry of translation is demonstrated by
ribozymes that promote the formation of amide linkages. For example, a ribozyme is selected that
forms a peptide linkage between a phenylalanine moiety attached to the ribozyme and biotinylated
amino acids. The biotinylated amino acid is activated by adenosine in a manner analogous to the
activation of amino acids by tRNA. A ribosome is a much more impressive example of such a
ribozyme. After solving the crystallographic structure of the ribosome it was clear that one of the
RNA molecules of its bigger subunit is responsible for the formation (catalysis) of peptides (amide
bond) (Fig. 31) [17].
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RNA World – The Origin of Life on Earth
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Fig. 30. SELEX obtained ribozymes possessing polymerization and ligation properties [19, 20]
RNA World – The Origin of Life on Earth
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33
Fig. 31. A ribosome structure and catalysis of peptide bond formation [17]
This means that modern protein synthesis (translation) still harbors remnants of RNA
catalysis. It is encouraging that, when the RNA of the ribosomal large subunit is stripped of all but a
few of its proteins, it still promotes a non-coded peptide bond formation.
7.5. Hypothetical first RNA-based organism
There is still no example of a ribozyme with sufficient significance and efficiency that it could
functionally substitute for an activity presumed by the ‘RNA world’ hypothesis necessary for the
creation of the first living organism. However, many ribozymes which have displayed properties
extremely useful but insufficient to create the first living system have been selected (Table 2, Fig. 30).
The construction of more-relevant activities will enable integration of the separate displays into
more sophisticated and convincing attractions, such as RNA-based metabolic pathways. Of course
there are no archeological fossils of RNA-based organisms. However, taking into account the general
rules characterizing living systems, the simplest model of an RNA-based organism has been proposed
[18]. An idea of the combination of two ribozyme activities has been inspired by properties of
vesicles made of long-chain fatty acids. One ribozyme (Rz2) would synthesize the vesicle membrane
component. A fatty acid precursor would be uptaken from the environment and processed
(hydrolysed) inside the vesicle by ribozyme Rz2 to become a component of the grooved lipid
34
RNA World – The Origin of Life on Earth
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membrane. A second ribozyme (Pol) of RNA replicase activity would replicate itself and the first
ribozyme (Fig. 32). As lipid vesicles grow they divide and create new vesicles. These vesicles retain
RNA oligonucleotides yet are somewhat permeable to nucleotides (NTPs), and thus it is possible to
imagine a vesicle system that could enclose the two ribozymes without excluding access to NTPs and
membrane precursors supplied as nutrients in the medium. If fed these nutrients, the vesicles with
ribozymes that synthesize membrane components would grow and divide. Long-term growth and
reproduction would depend on the activities of both ribozymes, and vesicles with improved
ribozymes would enjoy a reproductive advantage. Such improved ribozymes might emerge from the
variation generated from RNA replication errors. RNAs with entirely new activities might also
emerge.
Fig. 32. A model of the simplest RNA-based organism. Such organisms should display the basic features of life.
A polymerase ribozyme (Pol) uses nucleoside triphosphates (NTPs) to make more copies of itself and its
complement (cPol) in an autocatalytic cycle (purple arrows). The polymerase ribozyme also synthesizes
ribozyme 2 and its complement (Rz2 and cRz2, respectively; green arrows). Ribozyme 2 promotes a reaction
that facilitates growth and eventual division of the vesicle. In this example, ribozyme 2 converts a precursor
molecule (square heads) to the membrane component (round heads; red arrows). The vesicle membrane is
permeable to nucleoside triphosphates and membrane precursor but impermeable to polynucleotides [18].
7.6. RNA world relicts
There is no direct evidence (fossils) to prove the existence of the RNA world and RNA-based
organisms. A fully self-replicative RNA molecule has not been discovered yet. However, collected
data about evolution suggests that it is a conservative process that builds upon existing information
to create novel, better adapted structures and functions. If the RNA world existed and RNA was the
first molecule encoding information and the first catalytic molecule, then one can predict that
RNA World – The Origin of Life on Earth
by Piotr Mucha
35
vestiges of those early RNA structures and functions, molecular fossils, should be preserved in DNAbased organisms. The diversity of RNA types and ribonucleotides in modern cells and their
widespread involvement in key cellular functions provides much support for this hypothesis.
The hypothesis of the RNA world explains a number of biochemical observations correlated
with cell metabolism. The ribosome is the most important example. Most of the cellular processes
are catalyzed by enzymatic proteins. However, the key process of each cell–translation (protein
biosynthesis) is catalyzed by ribosomal RNA, a component of the large subunit of the ribosome. From
this point of view the ribosome is an ancient ribozyme. Beyond this fact there is much more evidence
of the presence of molecular fossils of the RNA world inside modern cells. Examples of molecular
fossils of the RNA world are listed below [11, 17, 18].
•
•
•
•
•
•
•
•
•
•
•
RNA is informational and catalytic in vivo; no other biomolecule has both properties.
The nucleotide sequences of RNAs common to all organisms (for example, rRNAs) are highly
conserved (similar) among the many different species studied, suggesting that RNA was a key
molecule present early in evolution.
RNA or ribonucleotides are involved in most critical cellular functions in all three domains of life:
- Adenosine triphosphate (ATP) is a universal energy carrier.
- Universal metabolic pathways employ adenine nucleotide coenzymes (NADH, NADPH, FAD,
CoA).
- Protein synthesis employs RNAs: mRNAs, rRNAs, and tRNAs.
- rRNA by itself can catalyze peptide bond formation.
- DNA synthesis requires the prior conversion of ribonucleotides to their deoxy form.
- The ribonucleotide uracil, found only in RNA, is the precursor for DNA’s thymine.
- RNA is the primer for DNA replication.
- Ribonucleotide derivatives function as key signaling molecules in the cell (for example,
cAMP, ATP).
RNAs function as primers in DNA replication and in reverse transcription of retroviral genomes.
tRNA-like molecules are involved in nontranslational (nonprogrammed) polymerizations (for
example, polypeptide antibiotic synthesis in bacteria).
A tRNA-like molecule may have given rise to the RNA component of telomerase, the enzyme
that maintains the ends of chromosomes.
Enzymatic processing of mRNAs involves other small RNAs (snRNPs, RNase P).
Protein sorting into the endoplasmic reticulum of all eukaryotes involves RNA(SRP-RNA).
Ribonucleotides are used to activate and carry sugars during polysaccharide synthesis.
RNA serves as a template to synthesize telomeric DNA fragments of chromosomes
Some viruses use reverse transcriptase to transcribe the genetic information stored in RNA to a
DNA molecule. Some others do not use DNA in a replication cycle at all. Whole genetic
information is stored and transferred by RNA molecules.
Although we do not have direct evidence of the RNA world existence at the beginnings of life,
molecular fossils found in present cells seem to confirm this hypothesis. Due to the fact that RNA was
not an ideal form of stored genetic information it was replaced by DNA. These events started the
evolution of DNA-based organisms. But this is a quite different story…
36
RNA World – The Origin of Life on Earth
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8. Literature
1.
Muriel Gargaud, Bernard Barbier, Hervé Martin and Jacques Reisse, Lectures in Astrobiology: Vol
I (Advances in Astrobiology and Biogeophysics), Springer, 1st ed., 2005
2.
Pekka Teerikorpi, Mauri Valtonen, K. Lehto, Harry Lehto, Gene Byrd, Arthur Chernin, The
Evolving Universe and the Origin of Life: The Search for Our Cosmic Roots, Springer, 1st ed.
2008.
3.
Hubble E. Effects of Red Shifts on the Distribution of Nebulae, Proc Natl Acad Sci U S A. 1936, 22,
621-627.
4.
Wilson RW, Penzias AA., Isotropy of cosmic background radiation at 4080 megahertz, Science,
1967, 156, 1100-1101.
5.
Woodruff T. Sullivan III, John Baross, Planets and Life: The Emerging Science of Astrobiology,
Cambridge University Press; 1st ed., 2007
6.
Horst Rauchfuss and T. N. Mitchell, Chemical Evolution and the Origin of Life, Springer, 1st ed.,
2008
7.
Piet Herdewijn, M. Volkan Kisakürek Origin of Life: Chemical Approach, Wiley-VCH; 1st ed., 2008
8.
Pier Luigi Luisi, The Emergence of Life: From Chemical Origins to Synthetic Biology Cambridge
University Press, 2010
9.
Ramberg PJ., The death of vitalism and the birth of organic chemistry: Wohler's urea synthesis
and the disciplinary identity of organic chemistry, Ambix, 2000, 47, 170-195.
10. Miller SL, Urey HC. Organic compound synthesis on the primitive earth, Science, 1959, 130, 245251.
11. David W. Deamer, Jack W Szostak, The Origins of Life, Cold Spring Harbor Laboratory Press, 1st
ed. 2010
12. Richard Egel, Dirk-Henner Lankenau, Armen Y. Mulkidjanian, Origins of Life: The Primal SelfOrganization, Springer; 1st ed., 2011
13. A. Ricardo, M. A. Carrigan, A. N. Olcott, S. A. Benner Borate Minerals Stabilize Ribose, Science,
2004, 303, 196.
14. Orgel LE, Prebiotic Chemistry and the Origin of the RNA World, Critical Reviews in Biochemistry
and Molecular Biology, 2004, 39, 99-123.
15. Matthew W. Powner, Beatrice Gerland, John D. Sutherland, Synthesis of activated pyrimidine
ribonucleotides in prebiotically plausible conditions, Nature, 2009,459, 259-262.
16. J. Tze-Fei Wong, Prebiotic Evolution and Astrobiology, Landes Bioscience; 1st ed., 2009
17. Raymond F. Gesteland The RNA World, Cold Spring Harbor Laboratory Press; 3rd ed., 2005
18. David P. Bartel and Peter J. Unrau, Trends in Genetics, 1999, 15, M9-M13.
19. Wendy K. Johnston, Peter J. Unrau, Michael S. Lawrence, Margaret E. Glasner, David P. Bartel,
RNA-Catalyzed RNA Polymerization: Accurate and General RNA-Templated Primer Extension,
Science, 2001, 1319-1325.
20. Yoshiya Ikawa, Kentaro Tsuda, Shigeyoshi Matsumura, Tan Inoue, De novo synthesis and
development of an RNA enzyme, PNAS, 2004, 101, 13750-13755.
RNA World – The Origin of Life on Earth
by Piotr Mucha
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