RNA world hypothesis
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[[Image:NA-comparedto-DNA thymineAndUracilCorrected.png|thumb|300px|RNA with its nitrogenous bases to the left and [[DNA]] to the right.]]
The '''RNA world hypothesis''' 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'' [[catalysis|catalyze]] reactions like [[protein]]s ([[enzyme]]s), may have supported cellular or pre-cellular life. Some hypotheses as to the [[origin of life]] present RNA-based catalysis and information storage as the first step in the evolution of cellular life.
The RNA world is proposed to have [[evolution|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 RNA in modern cells, in particular [[rRNA]] (RNA in the [[ribosome]] which [[catalyze]]s [[protein]] production), is the evolutionary remnant of the RNA world.
== 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.<ref>{{cite journal|title=The RNA World|journal=[[Nature (Journal)|Nature]]|first=Walter|last=Gilbert|authorlink=Walter Gilbert|month=Feb|year=1986|pages=618|volume=319|doi=10.1038/319618a0}}</ref> However, the idea of independent RNA life is older and can be found in [[Carl Woese]]'s ''The Genetic Code''<ref>{{cite book|title=The Genetic Code|first=Carl|last=Woese|authorlink=Carl Woese|publisher=Harper & Row|year=1968|month=Jan|isbn=978-0060471767}}</ref>. In [[1963]], 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]].
== Properties of RNA ==
The properties of RNA make 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.
A slightly different version of the hypothesis is that a different type of [[nucleic acid]], termed ''pre-RNA'', was the first one to emerge as a self-reproducing molecule, to be replaced by RNA only later. Such nucleic acids are sometimes more easily produced and/or polymerized under pre-biotic conditions. Suggestions for such nucleic acids include [[Peptide nucleic acid|PNA]], [[Threose nucleic acid|TNA]] or [[Glycerol nucleic acid|GNA]] <ref>{{cite journal|last=Orgel|first=Leslie|month=Nov|year=2000|title=A Simpler Nucleic Acid|journal=Science|volume=290|issue=5495|pages=1306–7|doi=10.1126/science.290.5495.1306|pmid=11185405}}</ref>
<ref>{{cite journal|author=Nelson, K.E.|coauthors=Levy, M.; Miller, S.L.
|title=Peptide nucleic acids rather than RNA may have been the first genetic molecule |year=2000|month=Apr|journal=Proc. Natl. Acad. Sci. USA|volume=97|issue=8|pages=3868–71|pmid=10760258|doi= 10.1073/pnas.97.8.3868 }}</ref>.
=== RNA as an enzyme ===
{{see|ribozyme}}
RNA enzymes, or ribozymes, are possible although not common in today's DNA-based life. However ribozymes play vital roles; ribozymes are essential components of the [[ribosome]], which is vital for protein synthesis. Many ribozyme functions are possible: nature widely uses [[RNA splicing|RNA self-splicing]] and [[directed evolution]] has created ribozymes with a variety of activities.
Among the enzymatic properties important for the beginning of life are:
*The ability to self-duplicate, or duplicate other RNA molecules. Relatively short RNA molecules that can duplicate others have been artificially produced in the lab. The shortest was 165-base long, though it has been estimated that only part of the bases were crucial for this function. One version, 189-base long, had fidelity of 98.9% <ref>W. K. Johnston, P. J. Unrau, M. S. Lawrence, M. E. Glasner and D. P. Bartel[http://www.sciencemag.org/cgi/content/abstract/292/5520/1319 RNA-Catalyzed RNA Polymerization: Accurate and General RNA-Templated Primer Extension]. Science 292, 1319 (2001)</ref>, which would mean it would make an exact copy of an RNA molecule as long as itself in one of every eight copies. This 189 base pair ribozyme could polymerize a template of at most 14 nucleotides in length, which is too short for replication, but a promising lead for further investigation. The longest primer extension by a ribozyme polymerase was 20 base pairs.<ref>Hani S. Zaher and Peter J. Unrau, [http://www.rnajournal.org.offcampus.lib.washington.edu/cgi/content/abstract/13/7/1017?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=zaher&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT Selection of an improved RNA polymerase ribozyme with superior extension and fidelity.] RNA (2007), 13:1017-1026 </ref>
*The ability to [[Catalysis|catalyze]] simple chemical reactions which would enhance the creation of molecules which are building blocks of RNA molecules—i.e., a strand of RNA which would make creating more strands of RNA easier. Relatively short RNA molecule with such abilities have been artificially formed in the lab.<ref>Huang, Yang, and Yarus, [http://www.chembiol.com/content/article/abstract?uid=PIIS1074552198902940 RNA enzymes with two small-molecule substrates]. Chemistry & Biology, Vol 5, 669-678, November 1998</ref> <ref>Unrau, P.J. and Bartel, D.P. (1998) [http://www.nature.com/nature/journal/v395/n6699/abs/395260a0.html RNA-catalysed nucleotide synthesis]. Nature 395, 260-263</ref>
*The ability to catalyse the formation of [[peptide bonds]], in order to produce short [[peptide]]s, or—eventually—full [[protein]]s. This is done in modern cells by [[ribosome]]s, a complex of two large RNA molecules known as [[rRNA]] and many proteins. The two rRNA molecules are thought to be responsible for its enzymatic activity. A much shorter RNA molecule has been formed in lab with the ability to form [[peptide bonds]], and it has been suggested that rRNA has evolved from a similar molecule.<ref>Zhang and Cech, [http://www.nature.com/nature/journal/v390/n6655/abs/390096a0.html Peptide bond formation by in vitro selected ribozymes]. Nature 390, 96-100</ref> It has also been suggested that amino acids may have initially been complexed with RNA molecules as [[Cofactor (biochemistry)|cofactor]]s enhancing or diversifying their enzymatic capabilities, before evolving to the more complex peptides. [[mRNA]] may have evolved from such RNA molecules, and tRNA from RNA molecules which had catalyzed amino acid transfer to them.<!-- this sentence is not too clear, and i don't know enough about this topic to rewrite it. someone else? --><ref>Szathmary E., [http://www.ingentaconnect.com/content/els/01689525/1999/00000015/00000006/art01730 The origin of the genetic code: amino acids as cofactors in an RNA world]. Trends in Genetics, Volume 15, Number 6, 1 June 1999 , pp. 223-229(7)</ref>
=== 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|RNA|DNA}}
The major difference between RNA and DNA 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 (i.e., 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 than DNA.
RNA also uses a different set of bases than DNA—adenine, guanine, cytosine and uracil, instead of adenine, guanine, cytosine and thymine. Chemically, uracil is similar to thymine, although its production requires less energy. 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 base pair|wobble]]) or '''AU''' [[base pair]].
==== Limitations of information storage in RNA ====
Storing large amounts of information in RNA is not easy. The chemical properties of RNA make large RNA [[molecule]]s inherently fragile, and they 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 susceptible to damage and breakdown by [[background radiation]].<ref>{{cite journal|title=Instability and decay of the primary structure of DNA|first=T|last=Lindahl|year=1993|month=Apr|journal=Nature|volume=362|issue=6422|pages=709–15|pmid=8469282|doi=10.1038/362709a0}}</ref> <ref>{{citejournal|title=Ancient DNA|journal=Scientific American|first=S|last=Pääbo|volume=269|pages=60–66|year=1993|month=Nov|issue=5}}</ref> These limitations do not make use of RNA as an information storage system 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.
== Support ==
The RNA World hypothesis is supported by RNA's ability to store, transmit, and duplicate [[genetics|genetic]] information, as [[DNA]] does. RNA can also act as a [[ribozyme]], a special type of [[enzyme]]. Because it can [[Reproduction|reproduce]] on its own, performing the tasks of both DNA and [[protein]]s (enzymes), RNA is believed to have once been capable of independent [[life]]. Further, while [[nucleotide]]s were not found in [[Miller-Urey]]'s [[abiogenesis|origins of life]] experiments, they were found by others' simulations. Experiments with basic ribozymes, like the viral RNA Qβ, have shown that simple self-replicating RNA structures can withstand even strong selective pressures (e.g., opposite-chirality chain terminators).<!-- I don't want to link to Spiegelman Monster here because I'm not sure that this is what's being talked about, but it appears to be. --><ref>Bell, Graham: The Basics of Selection. Springer, 1997.</ref>
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 (called [[ribonuclease]]s), 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.
== Difficulties ==
Since there are no known chemical pathways for the abiogenic synthesis of nucleotides from [[pyrimidine]] nucleobases [[cytosine]] and [[uracil]] under prebiotic conditions, it may be the case that nucleic acids did not contain the [[nucleobase]]s seen in life's nucleic acids.<ref>L. Orgel, The origin of life on earth. Scientific American. 271 (4) p. 81, 1994.</ref> Tellingly, the nucleoside cytosine has a half-life in isolation of 19 days at 100°C and 17,000 years in freezing water, which is still very short on the [[geologic time scale]].<ref>Matthew Levy and Stanley L. Miller, ''The stability of the RNA bases: Implications for the origin of life'', Proceedings of the National Academy of Science USA 95, 7933–7938 (1998)</ref> Others have questioned whether [[ribose]] and other backbone sugars could be stable enough to be found in the original genetic material.<ref>Larralde R, Robertson M P, Miller S L. Proc Natl Acad Sci USA. 1995;92:8158–8160.</ref> For example, the [[ester]] linkage of ribose and [[phosphoric acid]] in RNA is known to be prone to [[hydrolysis]].<ref> Lindahl T. Nature (London). 1993;362:709–715. </ref> Additionally, ribose must all be the same [[enantiomer]], because any nucleotides of the wrong [[chirality (chemistry)|chirality]] act as chain [[terminator (genetics)|terminators]].<ref>
{{cite journal|title=Chiral selection in poly(C)-directed synthesis of oligo(G)|author=Joyce GF|coauthors=Visser GM, van Boeckel CA, van Boom JH, Orgel LE, van Westrenen J.|journal=Nature|pmid=6462250|year=1984|month=Aug|issue=5978|volume=310|pages=602–4 | doi = 10.1038/310602a0 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
== 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 [[nucleotide]]s 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.
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.
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 acid]]s bind together (a process called [[peptide bond|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.
== 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 [[Eukaryote|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. <ref>{{cite journal | author = Zimmer C. | title = Did DNA come from viruses?| journal = [[Science (journal)|Science]] | volume = 312 | issue =5775 | pages = 870–2 | year =2006 | pmid = 16690855 | doi = 10.1126/science.312.5775.870}}</ref>
== Alternative hypotheses ==
As mentioned above, a different version of the same theory is "pre-RNA world", where a different nucleic acid is proposed to pre-date RNA. A proposed alternative is the peptide nucleic acid, [[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, because it contains neither. Threose nucleic acid ([[TNA (nucleic acid)|TNA]]) has also been proposed as a starting point, as has glycol nucleic acid ([[GNA (nucleic acid)|GNA]]).
A different—or complementary—alternative to the assembly of RNA is proposed in the [[PAH world hypothesis]].
The [[iron-sulfur world theory]] proposes that simple metabolic processes developed before genetic materials did, and these energy-producing cycles catalyzed the production of genes.
Yet another alternative theory to the RNA world hypothesis is the [[panspermia]] hypothesis. It discusses the possibility that the earliest life on this planet was carried here from somewhere else in the galaxy.
==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 acid]]s together into [[protein]]s, 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 ([[SnRNP]]s) in the processing of pre-mRNA and [[RNA editing]] and reverse transcription from RNA in [[Eucaryote]]s in the maintenance of [[telomeres]] in the [[telomerase]] reaction.
==See also==
*[[Abiogenesis]]
*[[Autocatalytic set]]
*[[The Major Transitions in Evolution]]
*[[Panspermia]]
==References==
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==Further reading==
<div class="references-small">
*{{cite book
|title=Genetic Takeover: And the Mineral Origins of Life
|first=A. G.
|last=Cairns-Smith
|year=1993
|isbn=0-521-23312-7
|publisher=Cambridge University Press
}}
*{{cite journal
|title=The origin of life on the Earth
|first=L. E.
|last=Orgel
|year=1994
|month=Oct
|journal=[[Scientific American]]
|pages=76–83
|volume=271
}}
*{{cite book
|title=Life Without Genes
|first=Adrian
|last=Woolfson
|year=2000
|month=Sep
|isbn=978-0006548744
|publisher=Flamingo
|location=London
}}
*{{cite journal
|title=The RNA World on Ice: A New Scenario for the Emergence of RNA Information
|first=Alexander V.
|last=Vlassov
|year=2005
|month=Jul
|journal=[[Journal of Molecular Evolution]]
|pages=264–273
|volume=61
|doi=10.1007/s00239-004-0362-7
}}
</div>
==External links==
*[http://nobelprize.org/chemistry/articles/altman/ "The RNA world" (2001)] by [[Sidney Altman]], on the Nobel prize website
*[http://nobelprize.org/nobel_prizes/chemistry/articles/cech/index.html "Exploring the new RNA world" (2004)] by [[Thomas R. Cech]], on the Nobel prize website
*[http://www.americanscientist.org/template/AssetDetail/assetid/21438?fulltext=true "The Beginnings of Life on Earth" (1995)] by [[Christian de Duve]] in ''American Scientist Online''
*[http://www.origins.rpi.edu/chem.html "The Formation of the RNA World"] by [[James P. Ferris]]
*[http://exploringorigins.org/ "Exploring Life's Origins: a Virtual Exhibit"]
* http://www.hhmi.org/bulletin/pdf/june2002/RNA.pdf HHMI bulletin
* http://www.panspermia.org/rnaworld.htm
* http://www.arn.org/docs/odesign/od171/rnaworld171.htm
* http://www.nature.com/nsmb/journal/v7/n1/full/nsb0100_5.html
[[Category:Origin of life]]
[[Category:RNA]]
[[Category:Biology theories]]
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