RNA Self Replication

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The RNA World

The idea that life began as a simple self replicating molecule is appealing because of its simplicity.  The RNA world hypothesis suggests that the origin of life was proceeded by a simple self replicating RNA molecule that through natural selection evolved into life as we know it today.

So consider the diagram below. Activated bases (ATP, CTP, UTP, and GTP) form on an existing RNA template. Can such a molecule really exist?

Figure 1 - RNA Self Replicator

rna-self-replication_small.GIF (7592 bytes)

 

  To answer this we need to consider the second law of thermodynamics. The first question we want to ask is does the above figure violate the second law. The answer is no.  The activated nucleotides have plenty of free energy (energy that can be used to do work), and when they join to the growing chain they  release two phosphate groups. The chemical bond that is broken in the process is a high energy bond.  The energy released by this broken bond drives the reaction forward (it supplies the energy required  for the growing RNA chain). Because this chemical reaction increases the entropy of the universe, at first glance,  figure 1 seems ok with the second law. So let us dig a little deeper.

Activated Nucleotides and RNA Self  Replication

 Where did the activated nucleotides come from? Figure 1 represents RNA self replication in a test tube - the activated nucleotides are supplied by a researcher in abundance.  Further, the researcher excludes all molecules that might impede the reaction. Thus, the researcher uses his knowledge of chemistry to add information to the system. This added information is necessary for RNA replication, and herein lies the problem with figure 1. This investigator interference nullifies the results of the experiment. Figure 1 is not realistic because the activated molecules would not exist in the primordial soup. And if by chance, any activated  molecules did exist, their concentration would be so dilute that replication would not take place under any plausible abiotic condition.

  In this example, the researcher has circumvented problems with the second law by using his own knowledge of chemistry. The researcher supplies the free energy needed to power the chemical reaction. He does this by using his knowledge of chemistry and molecular biology to reduce the entropy of the system at time zero. That is he adds activated molecules with high energy bonds, he excludes chemicals that might interfere with the RNA replication, and he carefully optimizes the conditions in the test tube to make replication more favorable. It is the researcher's knowledge of chemistry and molecular biology that allows this system to replicate.

  But any true self replicating molecule must be able to use its own knowledge to replicate. That is such a molecule must be able to synthesize the activated nucleotides and the nucleotides - if it cannot then it cannot replicate without the help of a researcher! Since there were no scientists on the earth 4 billion years ago to help the first RNA molecule replicate, figure 1 is not really relevant to the origin of life.

In figure 1, the entropy of the universe is increased when the activated molecules combine to form a chain. On the primitive earth, the elements that make up the activated nucleotides would exist. The phosphate groups would exist as phosphoric acid. The nitrogen in the nucleotides would exist as free atmospheric nitrogen and possible ammonia. The carbon in the nucleic acids would exist as carbon dioxide and possibly methane. The oxygen and hydrogen found in the nucleotides would exist as water. Activated nucleotides if they existed at all would be present in such low concentrations that RNA replication could not move forward.  So while figure 1 does not violate the second law, the starting conditions in figure 1 are just not relevant to the origin of life. These conditions are so unlikely that even given the size and age of the universe, these conditions  would not exist anywhere at anytime outside of the researcher's laboratory.

Do Energy Sources Solve the Problem?

Origin of life researchers often try to get around the above conclusion with the following argument:  the earth is an open system  and that sunlight or some other source (like electric sparks)  can provide the energy needed   to create the activated nucleotides. This idea seemed promising when Miller first synthesized amino acids in his spark chamber. But an amino acid is not an activated nucleotide, and 50 years of intense research have yet to elucidate a clear and plausible path for prebiotic activated nucleotide synthesis. The problem is pretty simple as both Sidney  Fox and Thaxton discussed in their books - sunlight and other energy sources interacting with complex molecules destroy them. So ATP in the primordial soup subjected to energy sources will decay into other elements like ammonia, phosphoric acid, and carbon dioxide. And this decay will dominate any possible route for synthesis. So these uncontrolled energy sources do more to hurt origin of life theories than they do to help.

Thaxton in the Mystery of life's Origin points out the following:

  • Energy sources destroy the necessary precursors much faster than they synthesize them. So if uv light manages to create 1 adenine  molecule and 1 ribose molecule in the earth's primitive ocean, then the next few rays of uv light will not result in a union of these two molecules but rather the destruction of both.
  • Given the slow path of synthesis and the fast routes for destruction, no mechanism for concentrating the necessary chemicals has yet been identified.  In other words, if  we could travel back in time and stock all small puddles with our special RNA template, it would never replicate because it would never be in a puddle with activated nucleotides. And if we put our special RNA template in the primitive ocean it would be destroyed by uv light (an energy source) before it found a single activated nucleotide.
  • Most importantly, the scientist is adding not only free energy but his own knowledge of chemistry. He eliminates side reactions by allowing only the chemicals that he needs. He concentrates and purifies these chemicals so that they will react. He is using his own knowledge of chemistry to substitute for the molecular knowledge that life needs to replicate.

   Thaxton correctly asserts that because science cannot conduct experiments that last for millions of years some level of acceleration by optimizing the starting conditions is acceptable. But he also was quick to say that the level of optimization needs to be curtailed so that it does not become excessive.

The primordial soup  is contraindicated by all  origin of life experiments. Nevertheless, the myth persists because naturalistic origin to life theories  requires this myth to be true.

Life Knows How to Use Energy Sources to do Work

Life is different than Miller's spark chamber in that it knows how to control energy sources to do work.  This requires molecular knowledge or useful information. That is life can use the energy from the sun or some other source to drive chemical reactions  creating useful molecules like the activated nucleotides that are needed for self replication. To accomplish this life uses teams of enzymes (see chapter 7).  The amino acid sequence of these enzymes is encoded in life's DNA. It is this useful information or molecular knowledge that allows life to exist.

The best analogy I can think of is that or a gas powered car in the desert that is out of gas. Because energy from the sun enters the system (which is the car in this example), the system is by definition an open one. The car cannot be driven to the gas station just because the sun is out. The sun provides plenty of free energy, but the car does not know how to use it. Life knows how to use energy. Plants tap into sunlight, and animals tap into the sugar that photosynthesis creates. Any self replicating molecule that hopes to mimic life must be able to do the same. So simple self replicators only exist in the lab and replicate only with the help of scientists. In nature, the first living thing must be robust. It must not only know how to synthesize activated nucleotides and nucleotides, but it must be able to couple this replication to a plentiful energy source. Without this ability it will violate the second law, and it cannot exist without the researchers continued love and nurturing. The above requirements for self replications rule out the RNA world.

The RNA world exists only in the minds of researchers and in textbooks. Because Figure 1 does not include the scientist or his interference, this figure is a perpetual motion machine. It is just like a gas powered car that runs forever with no gas. Thus, I am sure that science will never find a self replicating RNA molecule that can replicate without their help. Nevertheless, researchers  continue to look.

The RNA World and Investigator Interference 

The figure below shows what is required for  RNA to replicate in a test tube. A specially designed RNA template (see chapter 10)  is designed by the scientist. In figure 2,  the special RNA template has special notches along the top to prevent the activated nucleotides from rolling off as the scientist rolls them down the ramp. The balls on the floor represent chemicals like water, hydrogen, nitrogen, methane, and carbon dioxide. These chemicals are favored thermodynamically in an oxygen free atmosphere. Because these are useless to the scientist, he does not start with these chemicals but rather synthesizes nucleotides and then activates them to create activated nucleotides. When he rolls these down the ramp, they jump and fill the notches in the special RNA template. It is the scientist that supplies the free energy required for this reaction. Not sunlight, not electric sparks, not volcanic activity. It is the knowledge of the scientist that is important in this system. He sets the system up so that it will replicate. He provides the free energy in the form of activated nucleotides.

  This figure illustrates what Thaxton termed "investigator interference" in his ground breaking book the Mystery of Life's Origin. The activated nucleotides were not around in the primordial soup because the soup did not exist (see chapter 11).  This does not phase the scientist. He synthesizes and purifies these in his lab using his knowledge of chemistry. He then adds then to the test tube in abundance. When he finds that most RNA templates curl up on themselves and do not replicate under laboratory conditions, he conducts an extensive search to find one that will not curl up on itself. In this figure the free energy and information needed to replicate is supplied by the scientist. Once the scientist is removed from the figure, replication ceases.

So to re-iterate, the RNA world cannot exist unless an RNA molecule can couple its replication to an energy source like sunlight. This requirement does not mean that the RNA molecule can never exist, but it does prevent the RNA molecule from being simple. It must perform the function of several hundred enzymes ( see chapter 7, 13 and 14). This is problematic because it forces the chain to be long, reducing its probability of existence to zero.

Figure 2 - The RNA World and the Origin of Life

rna-world-origin-of-life

  The RNA world hypothesis does not help explain the origin of life because the starting conditions for the experiment can never exist on the primitive earth or anywhere in the universe. These conditions can only exist in test tubes with the aid of researchers. The origin of life remains a mystery.

Has Anyone Found a  Self- Replicating RNA Molecule

  This discussion is fairly lengthy and it is now time to wrap it up with perhaps the most damaging evidence against an RNA self replicator - nobody has ever found one. Forget replicating in nature under sub-optimal conditions. Why bother if these molecules can not replicate in a test tube under optimal conditions.

Molecules that can carry out step 1 in figure 1 have been found, and that is it. No step 2, 3 or 4.  So even   despite excessive investigator interference, science has yet to identify a single  self replicating RNA molecule. Joyce's article in  the RNA World is the best possible resource on this topic. The RNA world is not an intelligent design book. It is not a creationist book. It brings together a collection of works by leading origin of life researchers discussing the challenges facing the RNA world. In chapter 10, I summarize many of the issues brought up by Joyce and others in the RNA World. To keep it simple here, the reasons why a self replicating RNA molecule that can carry out all of the steps identified in figure 1 has not been found boils down to a handful of issues (each one seems insurmountable).

  • Once the complementary strand forms, it will never separate. So step 2 in figure 1 cannot happen. This of course prevents steps 3 and 4.
  • Most RNA templates curl up in such a way that activated nucleotides will not join and the strand does not grow.
  • Chain termination is a real issue. As the chain grows, it terminates prematurely.
  • If an RNA molecule helps catalyze its replication, then the active site on the molecule that is involved in replication cannot help replicate itself. Thus, we need to start with two self replicators not just one.

 

References:

Thaxton, Bradley, Olsen, The Mystery of Life’s Origin: Reassessing Current Theories, Philosophical Library, 1984.

Joyce and Orgel, The RNA World, Gesteland, Cech, Atkins, Cold Spring Harbor, “Prospects for Understanding the Origins of the RNA World,” 1999.

Navigation Menu Chapter 10


Chapter 10: Self Replicating Molecules (RNA and Proteins)
        A Self Replicating Peptide
        RNA Self Replication
        Molecular Knowledge in the Primordial Soup
        Self Replication and Perpetual Motion

PDF: Self Replicating Molecules and Systems (250 Kb)

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