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The RNA World Hypothesis is one of the widely accepted theories about the origin of life on earth. The complexity of modern life is one of the most astonishing aspects of our world. The way in which DNA, RNA, and proteins work together to create this complexity is still far from our understanding. One of most perplexing aspects of modern life revolves around the question: “How did it originate?” The RNA World Hypothesis proposes that RNA’s intrinsic properties allowed it generate life on its own. Since the formulation of the RNA World Hypothesis, research and experiments have been conducted in an attempt to support it. However, there are many seemingly paradoxical and highly improbable circumstances that would need to have occurred for the hypothesis to be valid.

Why RNA?

RNA is able to both store genetic information and perform enzymatic functions. This combination of functions allows RNA to potentially act as a template as well as a catalyst for its own replication, and is one of the primary reasons that RNA is thought to be the original polymer of life. It is hypothesized that RNA used these functions to generate a simple life cycle that then increased in complexity due variation and subsequent natural selection. Eventually, evolution could produce modern life. RNA is expected to have preceded DNA as the original information carrier because it requires less energy to form, and thymine (one of DNA’s possible bases) is formed from a chemical process that utilizes uracil (one of RNA’s possible bases.) DNA cannot catalyze reactions, so it could not have originated and replicated on its own before RNA. Ribonucleotides (not deoxyribonucleotides) are also utilized in the “most universal system of catabolism and energy supply of extant organisms.” (1) RNA is expected to have preceded proteins because X-ray calligraphy has shown (6) that RNA catalyzes the synthesis of proteins across all life forms within the ribosome. The proteins of the ribosome appear to function as structural support (Figure 1). DNA and proteins are hypothesized to have been additions to the RNA life system in accordance with reductive evolution of the RNA itself.

Major Discoveries Supporting the Hypothesis

Abiotic Formation and Polymerization

The discovery of a reaction that can create ribonucleotides without enzymes was a crucial discovery within the development of the RNA world hypothesis because it provided a possible way that RNA could have formed in an abiotic manner. In addition, “the discovery of non-enzymatic intramolecular (cys) and intermolecular (trans) rearrangements of RNA nucleotide sequences in aqueous solutions in the presence of magnesium ions via spontaneous transesterification reactions” has also provided tremendous support to the RNA World Hypothesis. This phenomenon gives a possible mechanism for the formation of RNA polymers from the oligoribonucleotides that could form on early earth. It also provides a way for there have been variances within these polymers, which would be necessary for natural selection to occur. There are multiple ways that transesterification reactions can occur (Figure 2).

Colony Formation

A second crucial discovery was that RNA could form molecular colonies on moist solid surfaces. In order for RNA to undergo natural selection, a form of compartmentalizing is necessary to create “individuals” that can be selected between, and will not break down once selected for.

Natural Selection

These discoveries correspond to the discovery that RNA can be selected for without the necessity of living cells through a repetition of stages of selection and amplification of sequences that perform advantageous functions.

Problems for the Hypothesis

The Problem with Water

The relationship between RNA and water creates a complex paradox for the RNA world hypothesis. Water is required for the formation of both the double helices of RNA required for reproduction as well as the folded structures of ribozymes. Conversely, is hydrolyzes RNA’s polyribonucleotide chain, terminates the ribose-phosphate backbone, and creates an unstable environment for RNA’s bases in both acidic and alkaline conditions. There have been attempts to explain how the RNA world could avoid the problem with water. One suggestion is that RNA molecules were stabilized on the surface of certain mineral clays. The problem with this suggestion is that the RNA would lose its mobility on the surface of the clays, leading to a reduction in functionality. Certain mineral clays can provide stability to RNA molecules, but they reduce their functionality by reducing their mobility. *(WP) In order to avoid this problem, there would need to be a cycle that places the RNA molecules on the surface of the clay for stability followed by a release into an aqueous phase to increase functionality(see). Another suggestion is that water was not the solvent that RNA was able to manifest and evolve in. Formamide is one suggested alternative solvent because RNA is stable within it. Unfortunately, formamide prevents RNA from forming the three dimensional structures, like double helices, that are necessary for the evolution of fictional RNA. (1) RNA double helices themselves are stable in water (5), but there still needs to be stability of the single strands for the progression of the RNA evolution. (5)

Viroids and the RNA World Today

Electron micrograph of the Ebola Zaire virus. This was the first photo ever taken of the virus, on 10/13/1976. By Dr. F.A. Murphy, now at U.C. Davis, then at the CDC.

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Legend/credit: Electron micrograph of the Ebola Zaire virus. This was the first photo ever taken of the virus, on 10/13/1976. By Dr. F.A. Murphy, now at U.C. Davis, then at the CDC.
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