Life From an RNA World: The Ancestor Within
Harvard University Press: 2010. 208 pp. $24.95/£18.95, €22.50 9780674050754 | ISBN: 978-0-6740-5075-4 Show
The RNA-world hypothesis proposes that today's DNA-based life forms evolved from earlier ones that were based on much simpler RNA molecules. Although no such RNA-based organism, or ribocyte, has yet been found, biochemist Michael Yarus marshals the theoretical considerations and lab experiments that lend support to this notion for the origin of life. Life From an RNA World is an unconventional book about RNA. Rather than opening with the central dogma and attendant teachings on molecular biology, Yarus uses evolution as a gateway. He then takes us on a journey through evolutionary time, concentrating on the roles of the various forms of RNA. Although the book reads like a collection of philosophical essays, its author is a proficient guide. Yarus first describes the basis of Darwinian evolution, in which the “secret is selection”. He explains how differences in the sequence of the RNA found in an organism's ribosomes — part of the protein-making machinery of the cell — are used to classify it into one of the three kingdoms of life. He introduces LUCA, the Last Universal Common Ancestor, “behind or before which lies the RNA world”. Various hypotheses about the origin of life are related in the book. One such is an idea that was independently reached by British geneticist J. B. S. Haldane and Russian biochemist Alexander Oparin. They suggested that the chemically reducing environment of the primitive Earth plus energy from ultraviolet light, lightning or other sources could generate several organic molecules. Chemists Stanley Miller and Harold Urey tested this at the University of Chicago in 1952 in their 'primordial soup experiments' that created amino acids from methane, ammonia, hydrogen and water when the mixture was exposed to an electrical discharge. The writing picks up when Yarus lays out the talents of RNA. As a molecule that is stable, single-stranded and able to form complex structures, it can assume many roles. Ribosomal and transfer RNAs provide the scaffolding to help make proteins and translate the information held in messenger RNA, which itself transcribes the information coded in DNA. The ribonucleotide building blocks that make up RNA are essential for enzyme function, and there are RNAs that have their own catalytic activity, known as ribozymes. Discovered by US molecular biologist Thomas Cech, these can cut themselves out from larger molecules. Other recent discoveries have revealed the existence of small RNAs, including microRNAs, that are intimately involved in controlling gene expression and translating messenger RNA. But the fact that RNA can adopt this vast catalogue of forms is insufficient evidence for a precursor RNA world. More compelling is the ability of RNA to evolve under selection pressure, as demonstrated in the elegant SELEX experiments done in Larry Gold's lab at the University of Colorado, Boulder. This evolutionary adaptability may be why it is the nucleic acid of choice for the genome of some of the most difficult and changeable pathogens, such as the influenza viruses. It is a key part of the argument that it was RNA that generated subsequent life forms, and that RNAs were a primitive system for making short chains of amino acids — a system that evolved to produce the protein-based structural and metabolic machinery found in organisms today. Further proof for the primitive RNA world could come from next-generation sequencing platforms that allow deep sampling of nucleic-acid populations from microorganisms in exotic locations, such as in deep-sea volcanic vents. But at present, the RNA world remains conjecture, based on powerful observations that this book captures. From The School of Biomedical Sciences Wiki 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 on the idea that RNA, as a message, led to proteins, which became catalysts. These proteins acted as the precursors for the production of 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. Contents
Evidence supporting the RNA worldThe 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 complementary 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. This means that the RNA molecule undergoes the process of natural selection, evolving into a more complex molecule[3]. and in this hypothesis eventually a precursor of life and life itself. In 1982 both Sidney Altman and Thomas Cech proved that RNA has the ability to act as a catalyst[4]. 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 demonstration of catalysis 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[5].[6]. It is also more likely that a single molecule was capable of self-replicating, rather than two different molecules being synthesized 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[7]. SELEX is a cycle used to extract oligonucleotides from an aptamer library, these nucleotides can either be of DNA or RNA origin. The first stage starts with a large aptamer library, then targetting molecules are added and bind to the complementary molecules. The assay is then washed to remove unbound aptamers, the targetted aptmers are left to be amplified by Polymerase Chain Reaction (PCR). The final stage is evaluation through binding assays or divergent assays, or the targets are regenerated[1]  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[8]. 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[9]. 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[10]. 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. However, it could be argued that, whilst the RNA was able to mutate over a series, the presence and requirement of the replicase enzyme weakens the study as a whole given that such a protein would not have been available in this pre-historic environment. 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. Evidence refuting the RNA worldAlthough 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 synthesize the component nucleotides of RNA under prebiotic conditions. However, recent developments by John Sutherland and his team have seen cytidine and uridine synthesised under early-Earth geochemical model conditions suggesting that RNA may have been able to spontaneously form under prebiotic conditions[11]. Another weakness of this theory is the susceptibility of an RNA-based system to catastrophes. If replication errors build up in the RNA to the point that they interfere with replication, the system will succumb to an error catastrophe[12]. If one RNA molecule mutates and begins to outcompete the rest of the population, the system will succumb to a selfish RNA catastrophe. The error and selfish RNA catastrophes are both caused by a single RNA molecule, so the probability of them occurring is directly proportional to population size. However, the probability of some other catastrophes is inversely proportional to population size, such as the population collapse catastrophe. This means that there is only a very small band of population sizes capable of avoiding all catastrophes and continuing on to produce more complex life[13]. Summary Table[14][15].
References:
What pieces of evidence support the RNA world hypothesis?The RNA world hypothesis is supported by the observations that ribosomes are ribozymes: the catalytic site is composed of RNA, and proteins hold no major structural role and are of peripheral functional importance. This was confirmed with the deciphering of the 3-dimensional structure of the ribosome in 2001.
What is evidence to the RNA world?There is now strong evidence indicating that an RNA World did indeed exist on the early Earth. The smoking gun is seen in the structure of the contemporary ribosome (Ban et al. 2000; Wimberly et al. 2000; Yusupov et al.
Which of the following supports the RNA world?RNA world hypothesis was given by Carl Woese, Francis Crick and Leslie Orgel in the 1960s before the discovery of DNA. This hypothesis states that earlier forms of life relied solely on RNA to store genetic information, duplicate itself and to catalyze chemical reactions.
Which observation of RNA provides the strongest evidence in support of the RNA world hypothesis?Perhaps the strongest evidence for the RNA World Hypothesis is the fact that the ribosome, a large molecular complex that assembles proteins, is a ribozyme.
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Which of the following is an additional piece of evidence in support of the RNA world hypothesis?
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