RNA world

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All modern organisms have DNA as a store of genetic information, RNA as a message and proteins as their major cellular catalyst. This shows that the organism from which all cellular life began had these properties, which is called 'LUCA', meaning Last Universal Common Ancestor. This is a very complicated model and there are many questions surrounding the origin of life, for example, how did it all start? Where did DNA come from, as proteins are involved in its replication? DNA codes for proteins, so how can proteins have been produced first, as they are believed to have been? What came first - polynucleotides or polypeptides?

The RNA world is the currently accepted hypothesis which answers these questions. This is based around the idea that RNA, as a message, led to proteins (this stage can be referred to as the RNP world), which became catalysts. This led to DNA, the long-term storage of genetic information. However the exact specificity of how this came about is still unclear. One concept is that life came from meteorites from outer space, as they have been observed to carry water, organic carbon, and biomolecules including amino acids. A similar concept is that life originates from deep sea vents, due to high hydrogen sulphide and mineral levels. One of the most popular concepts is that the early atmosphere composing of water, methane, ammonia, and hydrogen went on to produce the core biomolecules. This was demonstrated by Stanley Miller, who formulated an experiment mimicking the conditions of the early atmosphere discovered that after only a week 10-15% of the carbon was found to be part of organic compounds, 2% of that being amino acids.

Evidence supporting the RNA world

The main evidence supporting this hypothesis is the discovery that RNA can act as both a store of genetic information and as a cellular catalyst. The hypothesis is also supported by the fact that RNA can effectively self-replicate [1]using ribozymes such as the B6.16 ribozyme which was discovered in a random sequence of RNA ribozymes generated in conditions mimicking the pre-biotic environment. This ribozyme can faithfully add 20 nucleotides to a single-stranded RNA template molecule.

Both polypeptides and polynucleotides have the ability to store information by means of their amino acid sequences and their nucleotide sequences respectively but only polynucleotides have the ability to replicate. This is due to the fact that one polynucleotide strand can act as a template for another, by the complimentary base pairing of free nucleotides.[2] For this self-replication to be fast, efficient, and not prone to errors, a catalyst is required. This catalyst is the RNA molecule itself.

In 1982 both Sidney Altman and Thomas Cech proved that RNA has the ability to act as a catalyst.[3] RNA with catalytic activity is known as a ribozyme. One example of such a ribozyme is known as 'Tetrahymena RNA'. It was found that this RNA molecule could self-splice itself out of a gene without the use of any other enzymes. This was the first demonstartion of catalyis by an RNA molecule.  Despite the fact there are only a small number of ribozymes in modern day cells, many have been created in the lab, which can carry out a variety of different functions, including a ribozyme which can self-replicate.

Another major piece of evidence for the RNA hypothesis is the role of RNA in many important chemical processes in the body. DNA replication relies heavily on RNA as a primer for DNA polymerase and also to produce telomeres which prevent telomere shortening. RNA has also been found the catalyst in peptide bond formation therefore suggesting that it came before DNA and proteins.[4][5] It is also more likely that a single molecule was capable of self-replicating, rather than two different molecules being synthesised by random chemical reactions in the same place, at the same time and then coming together in a symbiotic relationship to create one system.

Furthermore, Systematic Evolution of Ligands by EXponential enrichment (SELEX) is used to identify useful RNA molecules from large random RNA samples; within one of these samples an aminoacyl RNA transferase ribozyme was discovered which could load amino acids onto its backbone and use them to increase the number of functions of the ribozyme. But it also suggested that the way in which these amino acids were held on the backbone could have acted as a proximity catalyst for the first polypeptides which have since evolved into modern proteins.[6]

Evidence from modern day life which supports the RNA World hypothesis can be seen by the presence of nucleotides in many important co-factors such as coenzymes A and B12, ATP, NAD and FAD. The nucleotides which reside within these molecules are thought to be remnants of ancestral ribozymes which have been integrated into life as we know it.[7]

Another piece of evidence that can be viewed in modern day life is the fact that there are so many structural similarities between a series of enzymes that are used during modern day replication and translation of DNA and RNA.  These include certain DNA Polymerases, viral and cellular RNA polymerases and reverse transcriptases.  These enzymes appear to be homologous and so it would appear as though they stem from a common ancestral RNA polymerase.[8]  This ancestral RNA polymerase would have been used during the RNA world and then later evolve into the other enzymes.

Given that there was no DNA in the proposed RNA world, RNA itself would be the genetic information store. In order to function as a genetic information store, it must have the ability to mutate so that RNA organisms are able to evolve and thus adapt to different environments and selection pressures. A 1967 study by Mills, Peterson and Spiegelman showed that mutations in RNA were possible[9]. They used an RNA bacteriophage named Qβ, and a replicase enzyme (which replicates RNA using a template), and they found that over a series of transfers, there were changes in the RNA nucleotide sequence. This shows that mistakes could happen during replication and that mutations within the Qβ genome could occur. Furthermore, they found that Qβ were less virulent in the later transfers, showing that their phenotype was altered by the mutations and that RNA was capable of evolving as a result.  

Finally, the RNA world could easily have evolved into our current day central dogma of biology, with DNA taking over as the main genetic store due to its increased stability. and proteins becoming the favoured catalyst due to their larger array of functions. Therefore, RNA remains as an intermediate molecule between the two systems.  

Although there are many pieces of evidence in support of the RNA world hypothesis, there are weaknesses in the theory. One major weakness was that scientists found it exceptionally difficult to synthesise the component nucleotides of RNA under prebiotic conditions. However, recent developments by John Sutherland and his team have saw cytidine and uridine synthesised under early-Earth geochemical model conditions suggesting that RNA may have been able to spontaneously form under prebiotic conditions[10].  

References:

  1. Zaher H S, Unrau P J, 2007, Selection of an improved RNA polymerase ribozyme with superior extension and fidelity, RNA, Volume 13, P1017-1026, The RNA Society.
  2. Alberts et al (2007). Molecular Biology of the Cell (Vol. 5th Ed). Garland Science.
  3. Ribosomes. (2014, November 05). Retrieved from British Society for Cell Biology: http://bscb.org/learning-resources/softcell-e-learning/ribosome/
  4. TERC. (2014, November 11). Retrieved from Genetics Home Referencing: http://ghr.nlm.nih.gov/gene/TERC
  5. Cooper. (2000). The Cell: A Molecular Approach (Vol. 2nd Ed). Sinauer Associates Inc
  6. Kun A, Szilagyi A, Konnyu B, Boza G, Zachar I, Szathmary E, 2015, The dynamics of the RNA world: insights and challenges, DNA habitats and their RNA inhabitants, Volume 1341, P75-95, Annals of the New York Academy of Sciences.
  7. White. (1976). Coenzymes as fossils of an earlier metabolic state. Journal of Molecular Evolution, 7(2), 101-104.
  8. Madame Curie Bioscience Database. Internet ed. Austin (TX): Landes Bioscience; 2000.
  9. Mills DR, Peterson RL, Spiegelman S (1967) “An extracellular Darwinian Experiment with a Self-duplicating Nucleic Acid Molecule,” Proceedings of the National Academy of Sciences, Vol. 58: pp 217-224
  10. Askt, J. (2014) RNA World 2.0, The Scientist. [Online]. Available from: http://www.the-scientist.com/?articles.view/articleNo/39252/title/RNA-World-2-0/ [Accessed 23 November 2015]



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