Editing RNA world (section)

== Support and difficulties ==
The RNA world hypothesis is supported by RNA's ability to do all three of to store, to transmit, and to duplicate [[genetics|genetic]] information, as [[DNA]] does, and to perform enzymatic reactions, like protein-based enzymes. Because it can carry out the types of tasks now performed by proteins and DNA, RNA is believed to have once been capable of supporting independent life on its own.<ref name="Atk06" /> Some [[virus]]es use RNA as their genetic material, rather than DNA.<ref>Patton, John T. Editor (2008). Segmented Double-stranded RNA Viruses: Structure and Molecular Biology. Caister Academic Press. Editor's affiliation: Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, MD 20892-8026. {{ISBN|978-1-904455-21-9}}</ref> Further, while [[nucleotide]]s were not found in experiments based on [[Miller–Urey experiment|Miller-Urey experiment]], their formation in prebiotically plausible conditions was reported in 2009;<ref name="Powner2009"/> a [[purine]] base, adenine, is merely a [[pentamer]] of [[hydrogen cyanide]], and it happens that this particular base is used as omnipresent energy vehicle in the cell: [[adenosine triphosphate]] is used everywhere in preference to [[guanosine triphosphate]], [[cytidine triphosphate]], [[uridine triphosphate]] or even [[deoxythymidine triphosphate]], which could serve just as well but are practically never used except as building blocks for nucleic acid chains. Experiments with basic ribozymes, like [[Bacteriophage Qβ]] RNA, 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.{{page needed|date=March 2021}}</ref>

Since there were no known chemical pathways for the abiogenic synthesis of nucleotides from [[pyrimidine]] nucleobases cytosine and uracil under prebiotic conditions, it is thought by some that nucleic acids did not contain these [[nucleobase]]s seen in life's nucleic acids.<ref>{{cite journal | vauthors = Orgel LE | title = The origin of life on the earth | journal = Scientific American | volume = 271 | issue = 4 | pages = 76–83 | date = October 1994 | pmid = 7524147 | doi = 10.1038/scientificamerican1094-76 | bibcode = 1994SciAm.271d..76O }}</ref> The nucleoside cytosine has a half-life in isolation of 19 days at {{convert|100|°C|°F|abbr=on}} and 17,000 years in freezing water, which some argue is too short on the [[geologic time scale]] for accumulation.<ref>{{cite journal | vauthors = Levy M, Miller SL | title = The stability of the RNA bases: implications for the origin of life | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 14 | pages = 7933–7938 | date = July 1998 | pmid = 9653118 | pmc = 20907 | doi = 10.1073/pnas.95.14.7933 | doi-access = free | bibcode = 1998PNAS...95.7933L }}</ref> Others have questioned whether [[ribose]] and other backbone sugars could be stable enough to be found in the original genetic material,<ref>{{cite journal | vauthors = Larralde R, Robertson MP, Miller SL | title = Rates of decomposition of ribose and other sugars: implications for chemical evolution | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 18 | pages = 8158–8160 | date = August 1995 | pmid = 7667262 | pmc = 41115 | doi = 10.1073/pnas.92.18.8158 | doi-access = free | bibcode = 1995PNAS...92.8158L }}</ref> and have raised the issue that all ribose molecules would have had to be the same [[enantiomer]], as any nucleotide of the wrong [[chirality (chemistry)|chirality]] acts as a chain [[terminator (genetics)|terminator]].<ref>{{cite journal | vauthors = Joyce GF, Visser GM, van Boeckel CA, van Boom JH, Orgel LE, van Westrenen J | title = Chiral selection in poly(C)-directed synthesis of oligo(G) | journal = Nature | volume = 310 | issue = 5978 | pages = 602–604 | year = 1984 | pmid = 6462250 | doi = 10.1038/310602a0 | s2cid = 4367383 | bibcode = 1984Natur.310..602J }}</ref>

Pyrimidine ribonucleosides and their respective nucleotides have been prebiotically synthesised by a sequence of reactions that by-pass free sugars and assemble in a stepwise fashion by including nitrogenous and oxygenous chemistries. In a series of publications, [[John Sutherland (chemist)|John Sutherland]] and his team at the School of Chemistry, [[University of Manchester]], have demonstrated high yielding routes to [[cytidine]] and [[uridine]] ribonucleotides built from small 2- and 3-carbon fragments such as [[glycolaldehyde]], [[glyceraldehyde]] or glyceraldehyde-3-phosphate, [[cyanamide]], and [[cyanoacetylene]]. One of the steps in this sequence allows the isolation of [[enantiomer|enantiopure]] ribose aminooxazoline if the enantiomeric excess of glyceraldehyde is 60% or greater, of possible interest toward biological homochirality.<ref>Carole Anastasi, Michael A. Crowe, Matthew W. Powner, John D. Sutherland "Direct Assembly of Nucleoside Precursors from Two- and Three-Carbon Units ''Angewandte Chemie International Edition'' '''45'''(37):6176–79, 2006.</ref> This can be viewed as a prebiotic purification step, where the said compound spontaneously crystallised out from a mixture of the other pentose aminooxazolines. Aminooxazolines can react with cyanoacetylene in a mild and highly efficient manner, controlled by inorganic phosphate, to give the cytidine ribonucleotides. Photoanomerization with [[UV light]] allows for inversion about the 1' anomeric centre to give the correct beta stereochemistry; one problem with this chemistry is the selective phosphorylation of alpha-cytidine at the 2' position.<ref name="pmid18798212">{{cite journal | vauthors = Powner MW, Sutherland JD | title = Potentially prebiotic synthesis of pyrimidine beta-D-ribonucleotides by photoanomerization/hydrolysis of alpha-D-cytidine-2'-phosphate | journal = ChemBioChem | volume = 9 | issue = 15 | pages = 2386–2387 | date = October 2008 | pmid = 18798212 | doi = 10.1002/cbic.200800391 | s2cid = 5704391 }}</ref> However, in 2009, they showed that the same simple building blocks allow access, via phosphate controlled nucleobase elaboration, to 2',3'-cyclic pyrimidine nucleotides directly, which are known to be able to polymerise into RNA.<ref name=Powner2009 /> Organic chemist Donna Blackmond described this finding as "strong evidence" in favour of the RNA world.<ref>{{cite journal |title=RNA world easier to make |author=Van Noorden R |journal=Nature |year=2009 |url=https://www.nature.com/news/2009/090513/full/news.2009.471.html |doi=10.1038/news.2009.471 |url-status=live |archive-url=https://web.archive.org/web/20090516205806/http://www.nature.com/news/2009/090513/full/news.2009.471.html |archive-date=2009-05-16}}</ref> However, John Sutherland said that while his team's work suggests that nucleic acids played an early and central role in the origin of life, it did not necessarily support the RNA world hypothesis in the strict sense, which he described as a "restrictive, hypothetical arrangement".<ref>{{citation | last = Urquhart | first = James | name-list-style = vanc | title = Insight into RNA origins | magazine = Chemistry World | publisher = Royal Society of Chemistry | date = 13 May 2009 |url=https://www.chemistryworld.com/news/insight-into-rna-origins/3002171.article | url-status = live | archive-url = https://web.archive.org/web/20151004071059/http://www.rsc.org/chemistryworld/News/2009/May/13050902.asp | archive-date = 4 October 2015 }}</ref>

The Sutherland group's 2009 paper also highlighted the possibility for the photo-sanitization of the pyrimidine-2',3'-cyclic phosphates.<ref name="Powner2009"/> A potential weakness of these routes is the generation of enantioenriched glyceraldehyde, or its 3-phosphate derivative (glyceraldehyde prefers to exist as its keto [[tautomer]] dihydroxyacetone).{{Citation needed|date=May 2009}}

On August 8, 2011, a report, based on [[NASA]] studies with [[meteorite]]s found on [[Earth]], was published suggesting building blocks of RNA (adenine, guanine, and related [[organic molecules]]) may have been formed in [[outer space]].<ref name="Callahan">{{cite journal | vauthors = Callahan MP, Smith KE, Cleaves HJ, Ruzicka J, Stern JC, Glavin DP, House CH, Dworkin JP | display-authors = 6 | title = Carbonaceous meteorites contain a wide range of extraterrestrial nucleobases | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 34 | pages = 13995–13998 | date = August 2011 | pmid = 21836052 | pmc = 3161613 | doi = 10.1073/pnas.1106493108 | doi-access = free | bibcode = 2011PNAS..10813995C }}</ref><ref name="Steigerwald">{{cite web | last = Steigerwald | first = John | name-list-style = vanc | title = NASA Researchers: DNA Building Blocks Can Be Made in Space |url=https://www.nasa.gov/topics/solarsystem/features/dna-meteorites.html | publisher = [[NASA]] | date = 8 August 2011 | access-date = 2011-08-10 | url-status = live | archive-url = https://web.archive.org/web/20150623004556/http://www.nasa.gov/topics/solarsystem/features/dna-meteorites.html | archive-date = 23 June 2015 }}</ref><ref name="DNA">{{cite web |author=ScienceDaily Staff |title=DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests |url=https://www.sciencedaily.com/releases/2011/08/110808220659.htm |date=9 August 2011 |website=[[ScienceDaily]] |access-date=2011-08-09 |url-status=live |archive-url=https://web.archive.org/web/20110905105043/https://www.sciencedaily.com/releases/2011/08/110808220659.htm |archive-date=5 September 2011 }}</ref> In 2017, research using a [[computer simulation|numerical model]] suggested that a RNA world may have emerged in warm ponds on the early Earth, and that meteorites were a plausible and probable source of the RNA building blocks ([[ribose]] and nucleic acids) to these environments.<ref>{{cite journal | vauthors = Pearce BK, Pudritz RE, Semenov DA, Henning TK | title = Origin of the RNA world: The fate of nucleobases in warm little ponds | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 43 | pages = 11327–11332 | date = October 2017 | pmid = 28973920 | pmc = 5664528 | doi = 10.1073/pnas.1710339114 | arxiv = 1710.00434 | doi-access = free | bibcode = 2017PNAS..11411327P }}</ref> On August 29, 2012, astronomers at [[Copenhagen University]] reported the detection of a specific sugar molecule, [[glycolaldehyde]], in a distant star system. The molecule was found around the [[protostar|protostellar]] binary ''IRAS 16293-2422'', which is located 400 light years from Earth.<ref name="NG-20120829">{{cite journal |title=Sugar Found In Space |journal=National Geographic |last=Than |first=Ker |date=August 29, 2012 |url=https://www.nationalgeographic.com/news/2012/8/120829-sugar-space-planets-science-life/ |access-date=August 31, 2012 |url-status=dead |archive-url=https://web.archive.org/web/20150714073830/http://news.nationalgeographic.com/news/2012/08/120829-sugar-space-planets-science-life/ |archive-date=July 14, 2015 }}</ref><ref name="AP-20120829">{{cite web |author=Staff |title=Sweet! Astronomers spot sugar molecule near star |url=http://apnews.excite.com/article/20120829/DA0V31D80.html |date=August 29, 2012 |publisher=[[AP News]] |access-date=August 31, 2012 |url-status=live |archive-url=https://web.archive.org/web/20150714101929/http://apnews.excite.com/article/20120829/DA0V31D80.html |archive-date=July 14, 2015 }}</ref> Because glycolaldehyde is needed to form RNA, this finding suggests that complex organic molecules may form in stellar systems prior to the formation of planets, eventually arriving on young planets early in their formation.<ref>{{cite journal | title = Detection of the simplest sugar, glycolaldehyde, in a solar-type protostar with ALMA | last1 = Jørgensen | first1 = J. K. | last2 = Favre | first2 = C. | last3 = Bisschop | first3 = S. | last4 = Bourke | first4 = T. | last5 = Dishoeck | first5 = E. | last6 = Schmalzl | first6 = M. | name-list-style = vanc | version = eprint | year = 2012 | url = http://www.eso.org/public/archives/releases/sciencepapers/eso1234/eso1234a.pdf | bibcode = 2012ApJ...757L...4J | volume = 757 | issue = 1 | pages = L4 | journal = The Astrophysical Journal Letters | doi = 10.1088/2041-8205/757/1/L4 | url-status = live | archive-url = https://web.archive.org/web/20150924021240/http://www.eso.org/public/archives/releases/sciencepapers/eso1234/eso1234a.pdf | archive-date = 2015-09-24 | arxiv = 1208.5498 | s2cid = 14205612 }}</ref> [[Nitrile]]s, key molecular precursors of the RNA World scenario, are among the most abundant chemical families in the universe and have been found in molecular clouds in the center of the Milky Way, protostars of different masses, meteorites and comets, and also in the atmosphere of Titan, the largest moon of Saturn.<ref>{{Cite journal |last1=Rivilla |first1=Víctor M. |last2=Jiménez-Serra |first2=Izaskun |last3=Martín-Pintado |first3=Jesús |last4=Colzi |first4=Laura |last5=Tercero |first5=Belén |last6=de Vicente |first6=Pablo |last7=Zeng |first7=Shaoshan |last8=Martín |first8=Sergio |last9=García de la Concepción |first9=Juan |last10=Bizzocchi |first10=Luca |last11=Melosso |first11=Mattia |date=2022 |title=Molecular Precursors of the RNA-World in Space: New Nitriles in the G+0.693−0.027 Molecular Cloud |journal=Frontiers in Astronomy and Space Sciences |volume=9 |page=876870 |doi=10.3389/fspas.2022.876870 |arxiv=2206.01053 |bibcode=2022FrASS...9.6870R |issn=2296-987X|doi-access=free }}</ref><ref>{{Cite web |date=2022-07-08 |title=Building blocks for RNA-based life abound at center of our galaxy |url=https://www.eurekalert.org/news-releases/957827 |access-date=2022-07-11 |website=EurekAlert! |language=en}}</ref>

A study in 2001 shows that [[nicotinic acid]] and its precursor, [[quinolinic acid]] can be "produced in yields as high as 7% in a six-step nonenzymatic sequence from [[aspartic acid]] and [[dihydroxyacetone phosphate]] (DHAP). The biosynthesis of ribose phosphate could have produced DHAP and other three carbon compounds. Aspartic acid could have been available from prebiotic synthesis or from the ribozyme synthesis of pyrimidines." This supports that NAD could have originated in the RNA world.<ref>{{Cite journal |last1=Cleaves |first1=H. James |last2=Miller |first2=Stanley L. |date=2001-01-01 |title=The Nicotinamide Biosynthetic Pathway Is a By-Product of the RNA World |url=https://doi.org/10.1007/s002390010135 |journal=Journal of Molecular Evolution |language=en |volume=52 |issue=1 |pages=73–77 |doi=10.1007/s002390010135 |pmid=11139296 |bibcode=2001JMolE..52...73C |s2cid=25458439 |issn=1432-1432}}</ref> RNA sequences at lengths of 30 nucleotides, 60 nucleotides, 100 nucleotides, and 140 nucleotides, were capable of catalysis of "the synthesis of three common coenzymes, CoA, NAD, and FAD, from their precursors, [[Phosphopantetheine|4‘-phosphopantetheine]], [[Nicotinamide mononucleotide|NMN]], and [[Flavin mononucleotide|FMN]], respectively".<ref>{{Cite journal |last1=Huang |first1=Faqing |last2=Bugg |first2=Charles Walter |last3=Yarus |first3=Michael |date=2000-12-01 |title=RNA-Catalyzed CoA, NAD, and FAD Synthesis from Phosphopantetheine, NMN, and FMN |url=https://pubs.acs.org/doi/10.1021/bi002061f |journal=Biochemistry |language=en |volume=39 |issue=50 |pages=15548–15555 |doi=10.1021/bi002061f |pmid=11112541 |issn=0006-2960}}</ref>