RNA with its nitrogenous bases to the left and DNA to the right.

The RNA world hypothesis is a theory which proposes that a world filled with RNA (ribonucleic acid) based life predates current DNA (deoxyribonucleic acid) based life. RNA, which can store information like DNA and catalyze reactions like proteins (enzymes), may have supported cellular or pre-cellular life. Some theories as to the origin of life present RNA-based catalysis and information storage as the first step in the evolution of cellular life. Image File history File links Thymine and Uracil were incorrectly depicted in the previous version. ... Image File history File links Thymine and Uracil were incorrectly depicted in the previous version. ... The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ... Ribonucleic acid (RNA) is a nucleic acid polymer consisting of nucleotide monomers, that acts as a messenger between DNA and ribosomes, and that is also responsible for making proteins out of amino acids. ... The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ... In chemistry and biology, catalysis is the acceleration (increase in rate) of a chemical reaction by means of a substance, called a catalyst, that is itself not consumed by the overall reaction. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... This article does not adequately cite its references or sources. ...

The RNA world is proposed to have evolved into the DNA and protein world of today. DNA, through its greater chemical stability, took over the role of data storage while protein, which is more flexible in catalysis through the great variety of amino acids, became the specialized catalytic molecules. The RNA world hypothesis suggests that messenger RNA (mRNA), the intermediate in protein production from a DNA sequence, is the evolutionary remnant of the RNA world. This article is about evolution in biology. ... The terms storage (U.K.) or memory (U.S.) refer to the parts of a digital computer that retain physical state (data) for some interval of time, possibly even after electrical power to the computer is turned off. ... The life cycle of an mRNA in a eukaryotic cell. ...

History

The phrase "RNA World" was first used by Nobel laureate Walter Gilbert in 1986, in a commentary on recent observations of the catalytic properties of various forms of RNA^[1] However, the idea of independent RNA life is older and can be found in Carl Woese's The Genetic Code^[2]. Five years earlier, the molecular biologist Alexander Rich, of the Massachusetts Institute of Technology, had posited much the same idea in an article he contributed to a volume issued in honor of Nobel-laureate physiologist Albert Szent-Györgyi. Walter Gilbert Walter Gilbert (born March 21, 1932) is an American physicist, biochemist, entrepreneur, and molecular biology pioneer. ... Carl Richard Woese (born July 15, 1928, Syracuse, New York) is an American microbiologist famous for defining the Archaea (a new domain or kingdom of life) in 1977 by phylogenetic taxonomy of 16S ribosomal RNA, a technique pioneered by Woese and which is now standard practice. ... The Massachusetts Institute of Technology (MIT) is a private, coeducational research university located in Cambridge, Massachusetts. ... Albert Szent-Györgyi at the time of his appointment to the National Institutes of Health Albert Szent-Györgyi (September 16, 1893 – October 22, 1986) was a Hungarian physiologist who won the Nobel Prize in Physiology or Medicine in 1937. ...

Properties of RNA

The properties of RNA makes the idea of the RNA world hypothesis conceptually possible, although its plausibility as an explanation for the origin of life is debated. RNA is known to form efficient catalysts and its similarity to DNA makes its ability to store information clear.

RNA as an enzyme

Main article: ribozyme

RNA enzymes, or ribozymes, are possible although not common in today's DNA-based life. However ribozymes play vital roles; a ribozyme, the ribosome, is vital for protein synthesis. Many ribozyme functions are possible, nature widely uses RNA self-splicing and directed evolution has created ribozymes with a variety of activities. // A ribozyme (from ribonucleic acid enzyme, also called RNA enzyme or catalytic RNA) is an RNA molecule that catalyzes a chemical reaction. ... A ribozyme, or RNA enzyme, is an RNA molecule that can catalyze a chemical reaction. ... Figure 1: Ribosome structure indicating small subunit (A) and large subunit (B). ... RNA splicing is the excision of introns from RNA during the formation of mRNA and the removal of introns from mRNA precursors and the reattachment or annealing of exons. ... Directed evolution is a method used in protein engineering to harness the power of Darwinian selection to evolve proteins with desirable properties not found in nature. ...

RNA in information storage

RNA is a very similar molecule to DNA, and only has two chemical differences. The overall structure of RNA and DNA are immensely similar - one strand of DNA and one of RNA can bind to form a double helical structure. This makes the storage of information in RNA possible in a very similar way to the storage of information in DNA.

Comparison of DNA and RNA structure

Main articles: RNA and DNA

The major difference is the presence of a hydroxyl group at the 2'-position of the ribose sugar in RNA. This group makes the molecule less stable; in flexible regions of an RNA molecule (ie. where not constrained in a double helix), it can chemically attack the adjacent phosphodiester bond to cleave the phosphodiester backbone. The hydroxyl group also forces the ribose into the C3'-endo sugar conformation unlike the C2'-endo conformation of the deoxyribose sugar in DNA. This forces a RNA double helix into a slightly different conformation to DNA. Ribonucleic acid (RNA) is a nucleic acid polymer consisting of nucleotide monomers, that acts as a messenger between DNA and ribosomes, and that is also responsible for making proteins out of amino acids. ... The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ...

RNA also uses a different set of bases to DNA - adenine, guanine, cytosine and uracil instead of adenine, guanine, cytosine and thymine. Chemically uracil is similar to thymine, although uses less energy to produce. In terms of base pairing this has no effect, adenine will readily bind uracil or thymine. Uracil is, however, one product of damage to cytosine making RNA particularly susceptible to mutations which replace a GC base pair with a GU (wobble) or AU base pair. Wobble base pairs for inosine Wobble base pairs for Uracil A wobble base pair is a G-U and I-U / I-A / I-C pair fundamental in RNA secondary structure. ... Base pairs, of a DNA molecule. ...

Limitations of information storage in RNA

Storage of large amounts of information in RNA is not easy. The chemical properties of RNA make large RNA molecules inherently fragile and can easily be broken down into their constituent nucleotides through hydrolysis. The aromatic bases also absorb strongly in the ultraviolet region, and would have been liable to damage and breakdown by background radiation^{[3] [4]}. These limitations do not make use of RNA as an information store impossible, simply energy intensive (to repair or replace damaged RNA molecules) and mutation prone. While this makes it unsuitable for current 'DNA optimised' life it may have been suitable for primitive life. In science, a molecule is a group of atoms in a definite arrangement held together by chemical bonds. ... Hydrolysis is a chemical reaction or process in which a chemical compound reacts with water. ... UV redirects here. ... Background radiation is the ionizing radiation emitted from a variety of natural and artificial radiation sources: sources in the Earth and from those sources that are incorporated in our food and water, which are incorporated in our body, and in building materials and other products that incorporate those radioactive sources...

Support

The RNA World hypothesis is supported by RNA's ability to store, transmit, and duplicate genetic information, as DNA does. RNA can also act as a ribozyme (an enzyme made of ribonucleic acid). Because it can reproduce on its own, performing the tasks of both DNA and proteins (enzymes), RNA is believed to have once been capable of independent life. Further, while nucleotides were not found in Miller-Urey's origins of life experiments, they were found by others' simulations, notably those of Joan Oro. Experiments with basic ribozymes, like the viral RNA Q-beta, have shown that simple self-replicating RNA structures can withstand even strong selective pressures (e.g., opposite-chirality chain terminators) (The Basics of Selection (London: Springer, 1997)). For a non-technical introduction to the topic, please see Introduction to genetics. ... The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ... // A ribozyme (from ribonucleic acid enzyme, also called RNA enzyme or catalytic RNA) is an RNA molecule that catalyzes a chemical reaction. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... For other uses, see Reproduction (disambiguation) Reproduction is the biological process by which new individual organisms are produced. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... For other uses, see Life (disambiguation). ... A nucleotide is a chemical compound that consists of a heterocyclic base, a sugar, and one or more phosphate groups. ... The Miller-Urey experiment attempts to recreate the chemical conditions of the primitive Earth in the laboratory, and synthesized some of the building blocks of life. ... This article focuses on modern scientific research on the origin of life. ... Joan Oró i Florensa (Lleida, Spain, October 26, 1923 - Barcelona, Spain, September 2, 2004) was a Catalan biochemist, whose research has been of importance in understanding the origin of life. ...

Additionally, in the past a given RNA molecule might have survived longer than it can today. Ultraviolet light can cause RNA to polymerize while at the same time breaking down other types of organic molecules that could have the potential of catalyzing the break down of RNA (ribonucleases), suggesting that RNA may have been a relatively common substance on early Earth. This aspect of the theory is still untested and is based on a constant concentration of sugar-phosphate molecules. Ribonuclease (RNase) is an enzyme that catalyzes the breakdown of RNA into smaller components. ...

Difficulties

The base cytosine does not have a plausible prebiotic simulation method because it easily undergoes hydrolysis. Cytosine is one of the 5 main nucleobases used in storing and transporting genetic information within a cell in the nucleic acids DNA and RNA. It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached (an amine group at position 4 and a keto group at...

Prebiotic simulations making nucleotides have conditions incompatible with those for making sugars (lots of formaldehyde). So they must somehow be synthesized, then brought together. However, they do not react in water. Anhydrous reactions bind with purines, but only 8% of them bind with the correct carbon atom on the sugar bound to the correct nitrogen atom on the base. Pyrimidines, however, do not react with ribose, even anhydrously. The chemical compound formaldehyde (also known as methanal) is a gas with a pungent smell. ... Purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. ... General Name, Symbol, Number carbon, C, 6 Chemical series nonmetals Group, Period, Block 14, 2, p Appearance black (graphite) colorless (diamond) Standard atomic weight 12. ... General Name, Symbol, Number nitrogen, N, 7 Chemical series nonmetals Group, Period, Block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring [1]. It is isomeric with two other forms of diazine. ...

Then phosphate must be introduced, but in nature phosphate in solution is extremely rare because it is so readily precipitated. After being introduced, the phosphate must combine with the nucleoside and the correct hydroxyl must be phosphorylated. Above is a ball-and-stick model of the inorganic hydrogenphosphate anion (HPO42−). Colour coding: P (orange); O (red); H (white). ... // Hydroxyl group The term hydroxyl group is used to describe the functional group -OH when it is a substituent in an organic compound. ... Phosphorylation is the addition of a phosphate (PO4) group to a protein or a small molecule. ...

For the nucleotides to form RNA, they must be activated themselves. Activated purine nucleotides form small chains on a pre-existing template of all-pyrimidine RNA. However, this does not happen in reverse because the pyrimidine nucleotides do not stack well. Category: ...

Additionally, the ribose must all be the same enantiomer, because any nucleotides of the wrong chirality act as chain terminators^[5]. In chemistry, enantiomers are stereoisomers that are mirror images of each other. ... The term chiral (pronounced ) is used to describe an object which is non-superimposable on its mirror image. ... In genetics, a terminator marks the end of a gene on the DNA for transcription. ...

A.G. Cairns-Smith in 1982 criticized writers for exaggerating the implications of the Miller-Urey experiment. He argued that the experiment showed, not the possibility that nucleic acids preceded life, but its implausibility. He claimed that the process of constructing nucleic acids would require 18 distinct conditions and events that would have to occur continually over millions of years in order to build up the required quantities.

Details of the RNA world

Mechanism for prebiotic RNA synthesis

Nucleotides are the fundamental molecules that combine in series to form RNA. They consist of a nitrogenous base attached to a sugar-phosphate backbone. RNA is made of long stretches of specific nucleotides arranged so that their sequence of bases carries information. The RNA world hypothesis holds that in the primordial soup / primordial sandwich there existed free-floating nucleotides. These nucleotides regularly formed bonds with one another, which often broke because the change in energy was so low. However, certain sequences of base pairs have catalytic properties that lower the energy of their chain being created, causing them to stay together for longer periods of time. As each chain grew longer it attracted more matching nucleotides faster, causing chains to now form faster than they were breaking down. A nucleotide is a chemical compound that consists of a heterocyclic base, a sugar, and one or more phosphate groups. ... The primordial sea, or primordial ocean, is a term applied collectively to the oceans of the earth at a time early in its history. ... The concept of the primordial sandwich was proposed by the chemist Günter Wächtershäuser to describe the possible origins of the first cell membranes (and therefore, the first cell). ...

These chains are proposed as the first, primitive forms of life. In an RNA world, different forms of RNA compete with each other for free nucleotides and are subject to natural selection. The most efficient molecules of RNA, the ones able to efficiently catalyze their own reproduction, survived and evolved, forming modern RNA. Darwins illustrations of beak variation in the finches of the Galápagos Islands, which hold 13 closely related species that differ most markedly in the shape of their beaks. ...

Competition between RNA may have favored the emergence of cooperation between different RNA chains, opening the way for the formation of the first proto-cell. Eventually, RNA chains randomly developed with catalytic properties that help amino acids bind together (peptide-bonding). These amino acids could then assist with RNA synthesis, giving those RNA chains that could serve as ribozymes the selective advantage. Eventually DNA, lipids, carbohydrates, and all sorts of other chemicals were recruited into life. This led to the first prokaryotic cells, and eventually to life as we know it. Phenylalanine is one of the standard amino acids. ... Peptides (from the Greek πεπτος, digestible), are the family of short molecules formed from the linking, in a defined order, of various α-amino acids. ...

Further developments

Patrick Forterre has been working on a controversial hypothesis, that viruses were instrumental in the transition from RNA to DNA and the evolution of Bacteria, Archaea, and Eukaryota. He believes the last common ancestor was RNA-based and evolved RNA viruses. Some of the viruses evolved into DNA viruses to protect their genes from attack. Through the process of viral infection into hosts the three domains of life evolved. ^[6] Phyla Actinobacteria Aquificae Chlamydiae Bacteroidetes/Chlorobi Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Lentisphaerae Nitrospirae Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Verrucomicrobia Bacteria (singular: bacterium) are unicellular microorganisms. ... Phyla / Classes Phylum Crenarchaeota Phylum Euryarchaeota     Halobacteria     Methanobacteria     Methanococci     Methanopyri     Archaeoglobi     Thermoplasmata     Thermococci Phylum Korarchaeota Phylum Nanoarchaeota Archaea (; from Greek αρχαία, ancient ones; singular Archaeum, Archaean, or Archaeon), also called Archaebacteria (), is a major division of living organisms. ... Kingdoms Animalia - Animals Fungi Plantae - Plants Protista Alternative Phylogeny Unikonta    Opisthokonta    Amoebozoa Bikonta    Apusozoa    Cabozoa       Rhizaria       Excavata    Corticata       Archaeplastida       Chromalveolata Animals, plants, fungi, and protists are eukaryotes (IPA: ), organisms with a complex cell or cells, where the genetic material is organized into a membrane-bound nucleus or nuclei. ...

Alternative theories

A proposed alternative to RNA in an "RNA World" is the peptide nucleic acid, PNA. PNA is more stable than RNA and appears to be more readily synthesized in prebiotic conditions, especially where the synthesis of ribose and adding phosphate groups are problematic. Threose nucleic acid (TNA) has also been proposed as a starting point, as has Glycol nucleic acid GNA. PNA is peptide nucleic acid, a chemical similar to DNA or RNA but differing in the composition of its backbone. ... TNA is threose nucleic acid, a chemical similar to DNA or RNA but differing in the composition of its backbone. ... GNA is glycol nucleic acid, a chemical similar to DNA or RNA but differing in the composition of its backbone. ...

A different alternative to the assembly of RNA is proposed in the PAH world hypothesis. The PAH world hypothesis proposes that the use of polycyclic aromatic hydrocarbon (PAH) was a means for a pre-RNA World basis for the origin of life. ...

Implications of the RNA world

The RNA world hypothesis, if true, has important implications for the very definition of life. For the majority of the time following the elucidation of the structure of DNA by Watson and Crick, life was considered as being largely defined in terms of DNA and proteins: DNA and proteins seemed to be the dominant macromolecules in the living cell, with RNA serving only to aid in creating proteins from the DNA blueprint.

The RNA world hypothesis places RNA at center-stage when life originated. This has been accompanied by many studies in the last ten years demonstrating important aspects of RNA function that were not previously known, and support the idea of a critical role for RNA in the functionality of life. In 2001, the RNA world hypothesis was given a major boost with the deciphering of the 3-dimensional structure of the ribosome, which revealed the key catalytic sites of ribosomes to be composed of RNA and for the proteins to hold no major structural role, and be of peripheral functional importance. Specifically, the formation of the peptide bond, the reaction that binds amino acids together into proteins, is now known to be catalyzed by an adenine residue in the rRNA: the ribosome is a ribozyme. This finding suggests that RNA molecules were most likely capable of generating the first proteins. Other interesting discoveries demonstrating a role for RNA beyond a simple message or transfer molecule include the importance of small nuclear ribonucleoproteins (SnRNPs) in the processing of pre-mRNA and RNA editing and reverse transcription from RNA in the maintenance of telomeres in the telomerase reaction. Figure 1: Ribosome structure indicating small subunit (A) and large subunit (B). ... Phenylalanine is one of the standard amino acids. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... This article or section does not adequately cite its references or sources. ... A non-coding RNA (ncRNA) is any RNA molecule that functions without being translated into a protein. ... // A ribozyme (from ribonucleic acid enzyme, also called RNA enzyme or catalytic RNA) is an RNA molecule that catalyzes a chemical reaction. ... SnRNPs (pronounced snurps), or small nuclear ribonucleoproteins, are particles which combine with pre-mRNA and various proteins to form spliceosomes (a type of large molecular complex). ... // Introduction The term RNA editing describes those molecular processes in which the information content is altered in a RNA molecule through a chemical change in the base makeup. ... A telomere is a region of highly repetitive DNA at the end of a chromosome, which functions as an aglet. ... Telomerase is an enzyme that adds specific DNA sequence repeats (TTAGGG in all vertebrates) to the 3 (three prime) end of DNA strands in the telomere regions, which are found at the ends of eukaryotic chromosomes. ...

See also

• Origin of life
• Autocatalytic set
• The Major Transitions in Evolution

This article does not adequately cite its references or sources. ... An autocatalytic set is a collection of entities, each of which is able to catalyze the creation of others within the set, such that as a whole, the set was able to catalyze its own replication. ... The Major Transitions in Evolution is a book written by John Maynard Smith and Eörs Szathmáry (Oxford University Press, 1995). ...

References

Walter Gilbert Walter Gilbert (born March 21, 1932) is an American physicist, biochemist, entrepreneur, and molecular biology pioneer. ... Nature is one of the most prominent scientific journals, first published on 4 November 1869. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Carl Richard Woese (born July 15, 1928, Syracuse, New York) is an American microbiologist famous for defining the Archaea (a new domain or kingdom of life) in 1977 by phylogenetic taxonomy of 16S ribosomal RNA, a technique pioneered by Woese and which is now standard practice. ... Science is the journal of the American Association for the Advancement of Science (AAAS). ... Scientific American is a popular-science magazine, published (first weekly and later monthly) since August 28, 1845, making it the oldest continuously published magazine in the United States. ...

External links

• The RNA World Website
• RNA@IGIB group at the Institute of Genomics and Integrative Biology working on RNA Biology

• "Self-replication: Even peptides do it" by Stuart A. Kauffman from Nature 382 August 8, 1996.
• "The RNA world" (2001) by Sidney Altman, on the Nobel prize website
• "Exploring the new RNA world" (2004) by Thomas R. Cech, on the Nobel prize website
• "The Beginnings of Life on Earth" (1995) by Christian de Duve in American Scientist Online
• "The Origin of Life on the Earth" by Leslie E. Orgel
• "The Formation of the RNA World" by James P. Ferris