Origin of Life What is Wrong with RNA World Hypothesis

 Origin of Life: What is Wrong with RNA World Hypothesis

Summary: RNA world hypothesis about origin of life was based on known properties of RNA but in formulating this hypothesis, limitations of RNA as a molecule capable of independently supporting life like activities were overlooked. These limitations are pointed out and DNA is suggested as the more plausible alternative.
The phrase "RNA World" was first used by Nobel laureate Walter Gilbert in 1986, in a commentary on recent observations of the catalytic properties of various forms of RNA.
The RNA world hypothesis is supported by RNA's ability to store, transmit, and duplicate genetic information, as DNA does. RNA can act as a ribozyme, a special type of enzyme. Because it can perform the tasks of both DNA and enzymes, RNA is believed to have once been capable of supporting independent life forms. Some viruses use RNA as their genetic material, rather than DNA.
RNA world hypothesis is further supported by computational ability of RNA. All the three i.e. DNA, RNA and Peptides have been shown to possess computational ability.
 RNA computing has been used to find solutions to Knight Problem in chess. 1024 strands were used. RNA computing correctly identified 43 out of 512 possible solutions with one error. Considering very high specificity of natural biochemical reactions, error checking and correcting mechanisms must co-exist with RNA computing. This explains need for existence of antisense RNA but at the same time raises doubts about ability of RNA alone to support a living system or life like activity.
Self replicative ability of RNA is not without limitations. Only short RNA molecules have been shown to possess this ability and with a questionable fidelity.  One version, 189-bases long, had fidelity of 98.9% which would mean it would make an exact copy of an RNA molecule as long as itself in one of every eight copies. This 189 base pair ribozyme could polymerize a template of at most 14 nucleotides in length, which is too short for replication. However this level of infidelity and limitation to self replication is far too high for living systems to bear. Just a single mutation affecting just one base pair in the entire genome is known to be catastrophic, therefore the kind of self replication seen under lab conditions does not support RNA world hypothesis.
RNA is much more unstable then DNA. This inherent instability of RNA is a further limitation to the ability of RNA to account for origin of life. Living organisms keep their identity and integrity over eons of time and across a vast number of generations. With no provision for RNA repair mechanisms of the kind seen for DNA in living systems, RNA is inherently incapable of performing this task.
 Autocatalysis: Julius Rebek and his colleagues have shown that in an experimental system containing amino acid adenosine and penta fluorophenyl ester with autocatalyst Amino Adenosine triacid ester variants (AATE variants) wherein a particular AATE variant autocatalysed its own synthesis. Therefore, this experiment demonstrates that nucleic acids were not absolute necessity for initial life like activity. Autocatalytic, autoreplicative property may be regarded as one of the properties of matter. These autocatalysts can give rise to population of entities with heredity which could exhibit mutual competition. By no stretch of imagination the particular AATE variant can be regarded as living. Therefore presence of autoreplicative and autocatalyzing property is insufficient to account for origin of life.
All the properties of RNA which lend credibility to RNA world hypothesis are present in DNA but without the limitations of RNA. Moreover DNA unlike RNA is able to form much longer sequences and is much more stable then RNA (DNA has propensity to spontaneous hydrolytic cleavage @1 per million base pair per day with highly efficient DNA repair mechanisms to maintain the status quo) and thus is not only capable of keeping identity and integrity of the organism but also capable of supporting phenomenon of inheritance. Also only DNA is capable of carrying the amount of information needed to support a living system by virtue of its ability to form long sequences of nucleotide bases.
RNA world hypothesis finds some support due to existence of RNA viruses and viroids which are not dependent on DNA during their entire life cycle. But available evidence indicates that these are able to survive only within eukaryotic cells which further imply that RNA can’t account for origin of life. Since life originated about 4 billion years back whereas origin of eukaryotes has been estimated to be only 1.6 – 2.1 billion years back.
Moreover the lab conditions under which various experiments in support of RNA world hypothesis have been conducted have not been shown to naturally exist. Even the nature of chemistry demonstrated in support of RNA world hypothesis is stochastic and not definitive and deterministic. Definitive and deterministic chemistry is the hall mark of biochemistry with no room for aberrant, random, side reactions.
Therefore life could have originated only as a DNA molecule because DNA is the only molecule capable of independently supporting all life like activities.   

Author: Dr Mahesh C. Jain is a practicing medical doctor and has written the book “Encounter of Science with Philosophy – A synthetic view”. The book begins with first chapter devoted to scientifically valid concept of God and then explains cosmic phenomena right from origin of nature and universe up to origin of life and evolution of man. The book includes several chapters devoted to auxiliary concepts and social sciences as corollaries to the concept of God. This is the only book which deals with origin of nature and universe from null. Twenty-ninth chapter of the book deals with the subject matter of ‘Origin of Life’.

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Whether Or Not Prebiotic Soup Was Ever Needed/Existed For Origin of Life

Whether Or Not Prebiotic Soup Was Ever Needed/Existed For Origin of Life

Summary: For most of modern theories of Origin of Life, Prebiotic Soup is the starting point and much of the research is focused on this point. However till date not an iota of evidence has been detected in support of existence of Prebiotic Soup at any time in the history of Earth. It is concluded that Prebiotic Soup was neither needed nor existed for Origin of Life on Earth. 

Darwin suggested that life could have begun in a warm little pond with all sorts of ammonia and phosphoric salts, light, heat, electricity present that a protein was formed ready to undergo still more complex changes. At the present day such matter would be instantly devoured or absorbed which would not have been the case before living creatures were formed.

 This gave rise to Primordial Soup Theory which suggests that life began in a pond or ocean as a result of the chemicals from the atmosphere and some form of energy to make amino acids; the building blocks of proteins, which would then evolve into all the species. This is supposed to happen at least 3.8 billion to 3.55 billion years ago.

This involves kaleidoscopic or random permutation and combination of chemicals with eventual selection and accumulation of useful permutations and combinations of chemicals so as to eventually give rise to origin as well as evolution of life.

Alexander Oparin in 1924 suggested the idea of Prebiotic Soup and today this is the starting point for most of modern theories of Origin of Life. Around the same time J.B.S. Haldane suggested that Earth’s Prebiotic oceans are different from today’s oceans – would have formed a hot dilute soup in which organic compounds could have formed. The underlying hypothesis held by Oparin and Haldane was that conditions on the primeval Earth favored chemical reactions that synthesized organic compounds from inorganic precursors. Arguing along the same line it has been speculated that once upon a time there existed organic matter on Earth in sufficient concentration that its spontaneous, kaleidoscopic random interactions ultimately led to Origin of Life. The principal difficulty with this line of thinking is lack of specificity of organic chemical reactions. This is quite unlike chemistry of life i.e. Biochemistry.

 Biochemist Robert Shapiro has summarized the "primordial soup" theory of Oparin and Haldane in its "mature form" as follows

1.   The early Earth had a chemically reducing atmosphere.

2.   This atmosphere, exposed to energy in various forms, produced simple organic compounds ("monomers").

3.   These compounds accumulated in a "soup", which may have been concentrated at various locations (shorelines, oceanic vents etc.).

4.   By further transformation, more complex organic polymers – and ultimately life – developed in the soup.

While steps 1-3 have been basically observed experimentally, step 4 has been criticized as simplistic - a stage of "then magic happens".

However even existence of chemically reducing atmosphere of Early earth has been doubted by geochemists. To quote:

“But is the “prebiotic soup” theory a reasonable explanation for the emergence of life? Contemporary geoscientists tend to doubt that the primitive atmosphere had the highly reducing composition used by Miller in 1953.” http://www.sciencemag.org/content/300/5620/745.full

Even need for step 3 is doubtful since Biological systems show extraordinary capacity to operate under very-very low concentrations of essential chemicals coupled with ability to concentrate essential chemicals as per the requirements of particular Biological Systems.

Since 1924, much work has been done to gather evidence in support of Primordial Soup Theory but till date not an iota of evidence has been discovered supporting Prebiotic Soup hypothesis or existence of Prebiotic Soup.

What has generally been overlooked by scientific community till date is the fact that Biochemistry or Chemistry of life is unique and distinctive to living state. It is totally devoid of randomness. Rather, Biological Systems in order to keep existence can’t permit random chemical reactions. Some of the salient features of Biochemistry are:

(I)                Specificity, accuracy and precision of reactions — unlike organic chemistry in which a large number of side reactions invariably occur during any organic reaction leading to formation of side products, in biochemistry reactions are highly specific, precise and accurate without any side reactions and free from side products. This is essential to avoid chaos in animate matter.

(II)             In biochemistry, all reactions take place under conditions of existence of given organism or conditions of its internal milieu which are often quite different from conditions in which similar inorganic and organic reactions proceed. Rationally speaking biochemical reactions must have originated under the conditions in which relevant organisms are usually found. Because of vast variation in habitat of organisms, the same potentiality is realized through differently structured enzymes effective under different conditions. Therefore, for evolution of Biochemistry, environment has never been an absolute constraint.

(III)           Biochemistry is deterministic. Deterministic character of chemistry of life is well exhibited by its properties such as specificity of intermolecular interactions, chemo selectivity, homochirality, stereo- specificity of biological molecules. Even the subsequent course of events has been essentially deterministic with a strong propensity to stabilization, fixation, preservation and propagation of useful past and present innovations. Biochemistry may have its roots in stochastic inanimate interaction of matter and energy but stochastic organic chemical reactions can’t account for specificity of reactions seen in biochemistry. Unfolding or evolution of biochemistry requires a surprising lack of side reactions (Smith and Morowitz). How this extraordinary specificity of chemical reactions is achieved in the absence of genes giving rise to catalytic polymers with three dimensional substrate pockets is still a matter of conjecture and contemplation.

So the key questions which we must address ourselves keeping in view homochirality of biological molecules are:

(i)                Why homochirality is so essential that it is a deterministic trait in entire biosphere or operates as a matter of law. Does it imply some constraints of molecular intelligence?

(ii)              How this deterministic homochirality was obtained and sustained, may be from a stochastic beginning and in a stochastic world? The answer to this might be simulation and induction, directed by utility.

All the experimental evidence gathered so far to bridge the gap between inanimate matter and animate matter belong to the realm of stochastic chemistry and the reaction products are devoid of life like intelligent molecular activity. This statement is applicable to both, abiotic monomer synthesis as well as abiotic polymer synthesis.

Time line of origin of life shows that it must have taken at least 200 Ma after formation of earth crust and oceans for life to appear. Life might have begun in the form of fossilized Cyanobacteria in Stomatolites which are known to occur as early as 3.85 Ga. Any theory of origin of life should be able to explain time involved in its origin. Therefore various experiments demonstrating synthesis of monomers over a very short period of time fail to explain as to why the time involved in origin of life was of the ~ 200 Ma. Hence, by whatever mechanisms life originated, it must have been very slow and cumulative over a period of time. Therefore the vast amount of experimental evidence only lends credibility to our belief in abiogenesis and that one day it shall be possible to provide detailed explanation of origin of life from inanimate matter but the accumulated evidence is otherwise not sufficient to explain phenomenon of origin of life. Considering the enormous time involved, processes leading to origin of life must be time dependent, extremely lengthy, cumulative, complex and intricate which at the same time are relatively stable, capable of fixation, preservation and propagation so that advances made are cumulative ultimately leading to origin of life. The process of origin of life should have proceeded through accumulation of a series of small discrete steps giving semblance of gradualism and continuity. Easy switching between inanimate behavior and life like activity should have been widely rampant in very-very early stages of origin of life. Vast distribution of life on earth shows that constraints like U.V. Radiation, Toxic effects of atmospheric oxygen against origin of life are just scientific fictions, since a large number of forms that could exist have evolved only after successfully meeting those constraints. Hence, these constraints, even though may be valid are not absolute or non-negotiable. Origin of life must involve origin of ways and means to circumvent and negotiate these constraints or to tolerate these constraints.

Therefore, life like activity began on earth at any point of time in its history when earth was capable of supporting or inducing life like activity due to some unknown cause-effect sequences. All kinds of life like activity began independent of each other wherever a source of energy, little moisture and relevant chemical elements were available even if in very-very minute amounts. Considering ubiquity of life on earth, environmental conditions could not have been a major deterrent. Rather they influenced type of life and life like activity to which every other type of life and life like activity has a relationship of adaptation and adaptability or harmony. Therefore, all life forms originated in such a way that they were ab initio adapted to conditions of their existence. Time and place has played a more significant role in determining type of life like activity and type of life through yet unknown cause-effect sequences. This is in conformity with time dependent increase in complexity of life on earth as per fossil records and place dependent biodiversity. Even Darwin observed that biodiversity on Galapagos Islands varied according to some geographical rule.

Summarizing all above, for Origin of Life neither Prebiotic Soup was ever needed nor could have ever existed. This is in conformity with all the experimental evidence gathered till date.

Author: Dr Mahesh C. Jain is a practicing medical doctor and has written the book “Encounter of Science with Philosophy – A synthetic view”. The book begins with first chapter devoted to scientifically valid concept of God and then explains cosmic phenomena right from origin of nature and universe up to origin of life and evolution of man. The book includes several chapters devoted to auxiliary concepts and social sciences as corollaries to the concept of God. This is the only book which deals with origin of nature and universe from null. Twenty-ninth chapter of the book deals with the subject matter of ‘Origin of Life’.

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