The RNA World Hypothesis

For centuries, humans have been enraptured with discovering how life on earth originated and what life was like during prehistoric times. There is no way to come up with a definitive answer to these questions, but countless theories about the origin of life, based on minimal amounts of evidence, have been proposed. Of these theories, the RNA world theory is the most popular one.

Premise

The premise of the theory is that life on Earth began with a simple RNA molecule that had the ability to replicate independently, with no help from other biological molecules such as enzymes. There is a focus on RNA rather than DNA because DNA synthesis relies upon enzymes such as DNA polymerase. Enzymes themselves are coded for by DNA molecules, meaning that without the presence of DNA, an enzyme molecule would not have existed and vice versa. This raises the question: what came first, the DNA or the enzyme? The concept of RNA being a primordial molecule was first proposed by scientists in the 1960s, namely the biochemist Leslie Orgel, microbiologist Carl Woese and molecular biologist Francis Crick.

Primordial soup

If RNA is to be considered a primordial molecule, how did it originate on Earth and how did it evolve? Many scientists strongly believe that RNA originated from RNA nucleotides, which emerged in a semi-liquid, soup-like substance known as the primordial soup. The theory of the primordial soup, initially proposed by Russian scientist Alexander Oparin and English geneticist John Haldane, suggests that because the Earth’s early atmosphere consisted of very little oxygen and large amounts of other gases, the carbon, nitrogen and hydrogen present could be rearranged chemically to form organic molecules essential to life, such as amino acids and nucleobases.

In 1953, American scientists Stanley Miller and Harold Urey conducted the now infamous “Miller-Urey experiment” to investigate this theory. They combined warm water with a mixture of the four major gases which were present in the Earth’s early atmosphere: methane, ammonia, water vapour and hydrogen. They also created constant lightning shocks using electrical charges pulsed through their artificial atmosphere in a closed apparatus. The warm water was used to simulate the primitive ocean, the gases were used to simulate the early atmosphere and the lightning shocks were used to simulate heat. After one week, Miller and Urey found that simple organic molecules, mainly amino acids, had formed under these simulated conditions, suggesting that abiogenesis (the evolution of life or living organisms from inorganic substances) was possible in prehistoric times.

More recently, a similar experiment performed by the organic chemist Thomas Carell yielded more interesting results relevant to the RNA world hypothesis. Carell and his research team have been able to demonstrate a chemical pathway that could have used inorganic substances to manufacture the primordial soup of the four RNA nucleobases - adenine, guanine, cytosine and uracil. The nucleobases were produced in such large amounts during this experiment that they could have accumulated thick crusts. It is believed that the intense heat and pressure of the conditions in the experiment and in prehistoric times could have resulted in the nucleobases reacting chemically to form the first RNA molecules. The results from this experiment have great value, adding credence to the RNA world hypothesis by suggesting that RNA could have been the origin of life rather than proteins.

Properties of RNA

The two key properties of the molecule that would have allowed it to be the primordial molecule of life are its ability to self-replicate and its ability to act as a catalyst. Self replication would have been critical for any primordial molecule as it would have had to be capable of replicating itself without any outside assistance. This is because there were no other molecules to assist the molecule at the time when life began.

In 1996, the biochemist Leslie Orgel discovered that activated RNA nucleotides were capable of being synthesized into RNA molecules up to 55 nucleotides long when added to volcanic clay. These activated nucleotides would have had additional phosphate molecules attached to them, providing enough energy to drive the reaction as opposed to ordinary nucleotides, which require an external input of energy to be joined in a chemical reaction to form RNA molecules. The phosphates added to these ordinary nucleotides are believed to have existed in the primordial soup of molecules, while the volcanic conditions are similar to what researchers believe prehistoric Earth would have resembled. This makes it possible that RNA molecules could have been synthesized from these activated nucleotides, hence becoming the primordial molecule due to their property of self-replication.

The property of RNA that allows it to catalyse chemical reactions has been proven by investigating the machinery of ribosomes. Ribosomes are the sites of protein synthesis found in all living cells. They are responsible for joining together amino acids carried by tRNA molecules in order to form a chain of polypeptides during the process of translation. Ribosomes consist of two subunits - a large subunit and a small subunit, which both contain proteins and ribosomal RNA of their own. It is this ribosomal RNA, or rRNA for short, that has been discovered to be a key player in the catalysis of protein synthesis. This has led to the conclusion that rRNA molecules are capable of catalysing biological reactions, and as a result, fall under the category of ribozymes (an RNA molecule that can catalyse biological reactions). The function of rRNA as a ribozyme in the ribosome is one of the strongest pieces of evidence to support the RNA world hypothesis.

Due to the fact that ribosomes are found in nearly all living cells, it is safe to say that they evolved before any of the other organelles found in modern cells. In fact, they are believed to have evolved around 4 billion years ago. As ribosomes contain RNA, it is believed that early life forms used RNA to perform vital life functions as opposed to proteins, which are used by modern organisms for the same purposes.

Evolution of DNA and proteins

If RNA was truly the primordial molecule, how did DNA and proteins evolve? Why now are DNA and proteins the basis of life for most modern cells and organisms? It seems that the answer to these questions is found in the weaknesses of RNA. DNA is more chemically stable than RNA, having a double helix structure as opposed to RNA’s single strand. As a result, DNA can store much larger sequences of information than RNA. As larger organisms evolved with larger genome sequences, DNA became the superior form of biological data storage. On the other hand, proteins have greater versatility and variability in comparison to RNA due to the virtually infinite number of combinations that can be achieved by 20 amino acids in comparison to the mere 256 combinations made by RNA nucleotides. This might be why proteins have superseded RNA as the catalytic molecule.

An alternative theory

Despite there being evidence to support the RNA world hypothesis, new evidence is emerging to disprove this hypothesis. Two papers published in the scientific journals: Molecular Biology and Evolution, and Biosystems, share the perspectives of professors Charles Carter Jr. and Peter Wills and their reasons for why the hypothetical RNA world would have been insufficient as the origin of life on Earth today. They have proposed an idea to replace the theory, named “the RNA-peptide world”, which is supported by computational and experimental evidence. The basis of this theory is that the interplay between RNA and peptides gave rise to Earth’s earliest life forms. One of the limitations to the original RNA world hypothesis, according to Carter and Wills, is that the catalytic ability of RNA is limited in comparison to that of peptide and polypeptide chains. They also state that the catalytic ability of RNA would have declined further due to the fluctuating temperatures on early Earth. Additionally, they question whether RNA would have evolved to incorporate peptides later on if RNA were the primordial molecule and did function to an optimal level. Furthermore, they suggest that peptides and RNA must have co-existed in order for the central principle of biology to be correct, where DNA is transcribed into RNA, which is then translated into peptides.

Despite there being alternative theories proposed, the RNA world theory seems to be the most promising at the moment, due to the relatively large amount of relevant research and experimental data to support it. There will always be some degree of uncertainty associated with theories about the origin of life, but the human race will continue to explore the most plausible explanations in order to obtain a logical answer which could be true to some extent.

References

• Alberts, B. et al. (2002) "The RNA World and the Origins of Life", Garland Science, p. Available at: https://www.ncbi.nlm.nih.gov/books/NBK26876/ (Accessed: 21 July 2020).

• Carter, C. and Wills, P. (2017) "Interdependence, Reflexivity, Fidelity, Impedance Matching, and the Evolution of Genetic Coding", Molecular Biology and Evolution, 35(2), pp. 269-286. doi: 10.1093/molbev/msx265.

• Lab-made primordial soup yields RNA bases (2019). Available at: https://www.nature.com/articles/d41586-019-02622-4 (Accessed: 27 July 2020).

• Marshall, M. (2020) First life: The search for the first replicator, New Scientist. Available at: https://www.newscientist.com/article/mg21128251-300-first-life-the-search-for-the-first-replicator/ (Accessed: 28 July 2020).

• RNA world (article) | Natural selection | Khan Academy (2020). Available at: https://www.khanacademy.org/science/ap-biology/natural-selection/origins-of-life-on-earth/a/rna-world (Accessed: 21 July 2020).

• RNA World Hypothesis | BioNinja (2020). Available at: https://ib.bioninja.com.au/standard-level/topic-1-cell-biology/15-the-origin-of-cells/rna-world-hypothesis.html (Accessed: 21 July 2020).

• RNA World Hypothesis is Wrong, Researchers Say - BioTechniques (2018). Available at: https://www.biotechniques.com/molecular-biology/saying-goodbye-to-the-rna-world-theory/ (Accessed: 29 July 2020).

• RNA world (2020). Available at: https://en.wikipedia.org/wiki/RNA_world (Accessed: 21 July 2020).

• Susha Cheriyedath, M. (2017) What is the RNA World Hypothesis?, News-Medical.net. Available at: https://www.news-medical.net/life-sciences/What-is-the-RNA-World-Hypothesis.aspx (Accessed: 21 July 2020).

• The End of the RNA World Is Near, Biochemists Argue | Quanta Magazine (2020). Available at: https://www.quantamagazine.org/the-end-of-the-rna-world-is-near-biochemists-argue-20171219/ (Accessed: 21 July 2020).

• What Is Primordial Soup? (2020). Available at: https://www.thoughtco.com/early-life-theory-of-primordial-soup-1224531 (Accessed: 27 July 2020).

• Wills, P. and Carter, C. (2018) "Insuperable problems of the genetic code initially emerging in an RNA world", Biosystems, 164, pp. 155-166. doi: 10.1016/j.biosystems.2017.09.006.