The RNA world is a hypothetical stage in the evolutionary history of life on Earth in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins . The term also refers to the hypothesis that posits the existence of this stage. Alexander Rich first proposed the concept of the RNA world in 1962, and Walter Gilbert coined the term in 1986.
184-501: Among the characteristics of RNA that suggest its original prominence are that: Although alternative chemical paths to life have been proposed, and RNA-based life may not have been the first life to exist, the RNA world hypothesis seems to be the most favored abiogenesis paradigm. However, even proponents agree that there is still has not conclusive evidence to completely falsify other paradigms and hypotheses. Regardless of its plausibility in
368-1038: A GC base pair with a GU ( wobble ) or AU base pair . RNA is thought to have preceded DNA, because of their ordering in the biosynthetic pathways. The deoxyribonucleotides used to make DNA are made from ribonucleotides, the building blocks of RNA, by removing the 2'-hydroxyl group. As a consequence, a cell must have the ability to make RNA before it can make DNA. The chemical properties of RNA make large RNA molecules inherently fragile, and they can easily be broken down into their constituent nucleotides through hydrolysis . 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 prone to mutation. While this makes it unsuitable for current 'DNA optimised' life, it may have been acceptable for more primitive life. Riboswitches have been found to act as regulators of gene expression, particularly in bacteria, but also in plants and archaea . Riboswitches alter their secondary structure in response to
552-467: A micelle . The next ribozyme discovered was the "tC19Z" ribozyme, which can add up to 95 nucleotides with a fidelity of 0.0083 mutations/nucleotide. Next, the "tC9Y" ribozyme was discovered by researchers and was further able to synthesize RNA strands up to 206 nucleotides long in the eutectic phase conditions at below-zero temperature, conditions previously shown to promote ribozyme polymerase activity. The RNA polymerase ribozyme (RPR) called tC9-4M
736-402: A 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. On August 29, 2012, astronomers at Copenhagen University reported the detection of a specific sugar molecule, glycolaldehyde , in a distant star system. The molecule
920-503: A prebiotic scenario, the RNA world can serve as a model system for studying the origin of life. If the RNA world existed, it was probably followed by an age characterized by the evolution of ribonucleoproteins ( RNP world ), which in turn ushered in the era of DNA and longer proteins. DNA has greater stability and durability than RNA, which may explain why it became the predominant information storage molecule. Protein enzymes may have replaced RNA-based ribozymes as biocatalysts because
1104-629: A terminator , truncating or permitting transcription respectively. Alternatively, riboswitches may bind or occlude the Shine–Dalgarno sequence , affecting translation. It has been suggested that these originated in an RNA-based world. In addition, RNA thermometers regulate gene expression in response to temperature changes. The RNA world hypothesis is supported by RNA's ability to do all three of to store, to transmit, and to duplicate genetic information, as DNA does, and to perform enzymatic reactions, like protein-based enzymes. Because it can carry out
1288-443: A "Pre-RNA world", where a metabolic system based on a different nucleic acid is proposed to pre-date RNA. A candidate nucleic acid is peptide nucleic acid ( PNA ), which uses simple peptide bonds to link nucleobases. PNA is more stable than RNA, but its ability to be generated under prebiological conditions has yet to be demonstrated experimentally. Threose nucleic acid ( TNA ) or glycol nucleic acid ( GNA ) have also been proposed as
1472-506: A SN 2 displacement, but the nucleophile comes from water or exogenous hydroxyl groups rather than RNA itself. The smallest ribozyme is UUU, which can promote the cleavage between G and A of the GAAA tetranucleotide via the first mechanism in the presence of Mn . The reason why this trinucleotide (rather than the complementary tetramer) catalyzes this reaction may be because the UUU-AAA pairing
1656-591: A biogenic origin. Parts of the Dresser formation preserve hot springs on land, but other regions seem to have been shallow seas. A molecular clock analysis suggests the LUCA emerged prior to the Late Heavy Bombardment (3.9 Gya). All chemical elements except for hydrogen and helium derive from stellar nucleosynthesis. The basic chemical ingredients of life – the carbon-hydrogen molecule (CH),
1840-443: A boundary is needed to separate ordered life processes from chaotic non-living matter. Irene Chen and Jack W. Szostak suggest that elementary protocells can give rise to cellular behaviors including primitive forms of differential reproduction, competition, and energy storage. Competition for membrane molecules would favor stabilized membranes, suggesting a selective advantage for the evolution of cross-linked fatty acids and even
2024-460: A catalyst and an informational polymer, making it easy for an investigator to produce vast populations of RNA catalysts using polymerase enzymes. The ribozymes are mutated by reverse transcribing them with reverse transcriptase into various cDNA and amplified with error-prone PCR . The selection parameters in these experiments often differ. One approach for selecting a ligase ribozyme involves using biotin tags, which are covalently linked to
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#17327655013042208-410: A cell's primary system of energy conversion. The mechanism, now ubiquitous in living cells, powers energy conversion in micro-organisms and in the mitochondria of eukaryotes, making it a likely candidate for early life. Mitochondria produce adenosine triphosphate (ATP), the energy currency of the cell used to drive cellular processes such as chemical syntheses. The mechanism of ATP synthesis involves
2392-471: A closed membrane in which the ATP synthase enzyme is embedded. The energy required to release strongly bound ATP has its origin in protons that move across the membrane. In modern cells, those proton movements are caused by the pumping of ions across the membrane, maintaining an electrochemical gradient. In the first organisms, the gradient could have been provided by the difference in chemical composition between
2576-464: A cryptic host over that extended period. Whether they are relics of that world or of more recent origin, their function as autonomous naked RNA is seen as analogous to that envisioned for an RNA world. Eigen et al . and Woese proposed that the genomes of early protocells were composed of single-stranded RNA, and that individual genes corresponded to separate RNA segments, rather than being linked end-to-end as in present-day DNA genomes. A protocell that
2760-407: A damaged RNA segment to be replaced by an additional replication of its homolog. However, for such a simple organism, the proportion of available resources tied up in the genetic material would be a large fraction of the total resource budget. Under limited resource conditions, the protocell reproductive rate would likely be inversely related to ploidy number. The protocell's fitness would be reduced by
2944-463: 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, differing only by a methyl group , and its production requires less energy. In terms of base pairing, this has no effect. Adenine readily binds uracil or thymine. Uracil is, however, one product of damage to cytosine that makes RNA particularly susceptible to mutations that can replace
3128-530: A diverse array of amino acids. Later work has focused on two other potential reducing environments: outer space and deep-sea hydrothermal vents. Soon after the Big Bang , which occurred roughly 14 Gya, the only chemical elements present in the universe were hydrogen , helium , and lithium , the three lightest atoms in the periodic table. These elements gradually accreted and began orbiting in disks of gas and dust. Gravitational accretion of material at
3312-546: A double helix, the 2' hydroxyl 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 an RNA double helix to change from a B-DNA structure to one more closely resembling A-DNA . RNA also uses
3496-508: A foreign idea that they had difficulty publishing their findings. The following year , Altman demonstrated that RNA can act as a catalyst by showing that the RNase-P RNA subunit could catalyze the cleavage of precursor tRNA into active tRNA in the absence of any protein component. Since Cech's and Altman's discovery, other investigators have discovered other examples of self-cleaving RNA or catalytic RNA molecules. Many ribozymes have either
3680-461: A habitable world is formed with a supply of minerals and liquid water. Prebiotic synthesis creates a range of simple organic compounds, which are assembled into polymers such as proteins and RNA. On the other side, the process after the LUCA is readily understood: biological evolution caused the development of a wide range of species with varied forms and biochemical capabilities. However, the derivation of living things such as LUCA from simple components
3864-472: A hairpin – or hammerhead – shaped active center and a unique secondary structure that allows them to cleave other RNA molecules at specific sequences. It is now possible to make ribozymes that will specifically cleave any RNA molecule. These RNA catalysts may have pharmaceutical applications. For example, a ribozyme has been designed to cleave the RNA of HIV . If such a ribozyme were made by a cell, all incoming virus particles would have their RNA genome cleaved by
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#17327655013044048-549: A hot acidic lake in Lassen Volcanic National Park, California, they uncovered evidence that a simple DNA virus had acquired a gene from a completely unrelated RNA-based virus. Virologist Luis Villareal of the University of California Irvine also suggests that viruses capable of converting an RNA-based gene into DNA and then incorporating it into a more complex DNA-based genome might have been common in
4232-410: A laboratory setting. Self-assembled vesicles are essential components of primitive cells. The theory of classical irreversible thermodynamics treats self-assembly under a generalized chemical potential within the framework of dissipative systems . The second law of thermodynamics requires that overall entropy increases, yet life is distinguished by its great degree of organization. Therefore,
4416-473: A large range of sugars. Both TAP and melamine base pair with barbituric acid. All three spontaneously form nucleotides with ribose. One of the challenges posed by the RNA world hypothesis is to discover the pathway by which an RNA-based system transitioned to one based on DNA. Geoffrey Diemer and Ken Stedman, at Portland State University in Oregon, may have found a solution. While conducting a survey of viruses in
4600-411: A lethal damage, multiple infection can lead to reactivation providing that at least one undamaged copy of each virus gene is present in the infected cell. This phenomenon is known as "multiplicity reactivation". Multiplicity reactivation has been reported to occur in influenza virus infections after induction of RNA damage by UV-irradiation , and ionizing radiation. Patrick Forterre has been working on
4784-417: A likely constituent of Earth's primordial sea. PAHs have been detected in nebulae , and in the interstellar medium , in comets, and in meteorites. The PAH world hypothesis posits PAHs as precursors to the RNA world. A star, HH 46-IR, resembling the sun early in its life, is surrounded by a disk of material which contains molecules including cyanide compounds, hydrocarbons , and carbon monoxide. PAHs in
4968-584: A living organism creates order in some places (e.g. its living body) at the expense of an increase of entropy elsewhere (e.g. heat and waste production). Multiple sources of energy were available for chemical reactions on the early Earth. Heat from geothermal processes is a standard energy source for chemistry. Other examples include sunlight, lightning, atmospheric entries of micro-meteorites, and implosion of bubbles in sea and ocean waves. This has been confirmed by experiments and simulations. Unfavorable reactions can be driven by highly favorable ones, as in
5152-439: A membrane site and a specific compound trapped in the vesicle. Such site/compound pairs are transmissible to the daughter vesicles leading to the emergence of distinct lineages of vesicles, which would have allowed natural selection . A protocell is a self-organized, self-ordered, spherical collection of lipids proposed as a stepping-stone to the origin of life. A functional protocell has (as of 2014) not yet been achieved in
5336-466: A model system, there is no requirement for divalent cations in a five-nucleotide RNA catalyzing trans - phenylalanation of a four-nucleotide substrate with 3 base pairs complementary with the catalyst, where the catalyst/substrate were devised by truncation of the C3 ribozyme. The best-studied ribozymes are probably those that cut themselves or other RNAs, as in the original discovery by Cech and Altman. However, ribozymes can be designed to catalyze
5520-399: 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 (or sandwich ), there existed free-floating nucleotides. These nucleotides regularly formed bonds with one another, which often broke because the change in energy
5704-403: A novel hypothesis, called "three viruses, three domains": that viruses were instrumental in the transition from RNA to DNA and the evolution of Bacteria , Archaea , and Eukaryota . He believes the last universal 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
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5888-837: A number of possible routes. Some center on high temperature/concentration conditions in which condensation becomes energetically favorable, while others focus on the availability of plausible prebiotic condensing agents. Experimental evidence for the formation of peptides in uniquely concentrated environments is bolstered by work suggesting that wet-dry cycles and the presence of specific salts can greatly increase spontaneous condensation of glycine into poly-glycine chains. Other work suggests that while mineral surfaces, such as those of pyrite, calcite, and rutile catalyze peptide condensation, they also catalyze their hydrolysis. The authors suggest that additional chemical activation or coupling would be necessary to produce peptides at sufficient concentrations. Thus, mineral surface catalysis, while important,
6072-521: A primordial molecule can be found in papers by Francis Crick and Leslie Orgel , as well as in Carl Woese 's 1967 book The Genetic Code . Hans Kuhn in 1972 laid out a possible process by which the modern genetic system might have arisen from a nucleotide-based precursor, and this led Harold White in 1976 to observe that many of the cofactors essential for enzymatic function are either nucleotides or could have been derived from nucleotides. He proposed
6256-400: A professor at Yale University , was studying the way tRNA molecules are processed in the cell when he and his colleagues isolated an enzyme called RNase-P , which is responsible for conversion of a precursor tRNA into the active tRNA. Much to their surprise, they found that RNase-P contained RNA in addition to protein and that RNA was an essential component of the active enzyme. This was such
6440-533: A range of reactions, many of which may occur in life but have not been discovered in cells. RNA may catalyze folding of the pathological protein conformation of a prion in a manner similar to that of a chaperonin . RNA can also act as a hereditary molecule, which encouraged Walter Gilbert to propose that in the distant past, the cell used RNA as both the genetic material and the structural and catalytic molecule rather than dividing these functions between DNA and protein as they are today; this hypothesis
6624-423: A replicator molecule. Possible precursors to protein synthesis include the synthesis of short peptide cofactors or the self-catalysing duplication of RNA. It is likely that the ancestral ribosome was composed entirely of RNA, although some roles have since been taken over by proteins. Major remaining questions on this topic include identifying the selective force for the evolution of the ribosome and determining how
6808-426: A ribozyme is capable of invading duplexed RNA, rearranging into an open holopolymerase complex, and then searching for a specific RNA promoter sequence, and upon recognition rearrange again into a processive form that polymerizes a complementary strand of the sequence. This ribozyme is capable of extending duplexed RNA by up to 107 nucleotides, and does so without needing to tether the sequence being polymerized. Since
6992-473: A sapphire substrate with a web of thin cracks under a heat flow, similar to the environment of deep-ocean vents , as a mechanism to separate and concentrate prebiotically relevant building blocks from a dilute mixture, purifying their concentration by up to three orders of magnitude. The authors propose this as a plausible model for the origin of complex biopolymers. This presents another physical process that allows for concentrated peptide precursors to combine in
7176-436: A scenario whereby the critical electrochemistry of enzymatic reactions would have necessitated retention of the specific nucleotide moieties of the original RNA-based enzymes carrying out the reactions, while the remaining structural elements of the enzymes were gradually replaced by protein, until all that remained of the original RNAs were these nucleotide cofactors, "fossils of nucleic acid enzymes". The properties of RNA make
7360-497: A series of publications, 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 enantiopure ribose aminooxazoline if
7544-505: A short (five-nucleotide) segment of RNA. In March 2015, NASA scientists reported that, for the first time, complex DNA and RNA organic compounds of life , including uracil, cytosine, and thymine, have been formed in the laboratory under conditions found only in outer space , using starting chemicals, like pyrimidine , found in meteorites . Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), may have been formed in red giant stars or in interstellar dust and gas clouds, according to
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7728-403: A small molecule ligand to regulate translation. While there are many known natural riboswitches that bind a wide array of metabolites and other small organic molecules, only one ribozyme based on a riboswitch has been described: glmS . Early work in characterizing self-cleaving riboswitches was focused on using theophylline as the ligand. In these studies, an RNA hairpin is formed which blocks
7912-465: A starting point, and like PNA, also lack experimental evidence for their respective abiogenesis. An alternative—or complementary—theory of RNA origin is proposed in the PAH world hypothesis , whereby polycyclic aromatic hydrocarbons ( PAHs ) mediate the synthesis of RNA molecules. PAHs are the most common and abundant of the known polyatomic molecules in the visible Universe and are a likely constituent of
8096-418: A sugar molecule and RNA precursor, has been detected in regions of space including around protostars and on meteorites. As early as the 1860s, experiments demonstrated that biologically relevant molecules can be produced from interaction of simple carbon sources with abundant inorganic catalysts. The spontaneous formation of complex polymers from abiotically generated monomers under the conditions posited by
8280-468: A transient diploid. The retention of the haploid state maximizes the growth rate. The periodic fusions permit mutual reactivation of otherwise lethally damaged protocells. If at least one damage-free copy of each RNA gene is present in the transient diploid, viable progeny can be formed. For two, rather than one, viable daughter cells to be produced would require an extra replication of the intact RNA gene homologous to any RNA gene that had been damaged prior to
8464-476: A turbulent atmosphere, and a hydrosphere subject to intense ultraviolet light from a T Tauri stage Sun , from cosmic radiation , and from continued asteroid and comet impacts. Despite all this, niche environments likely existed conducive to life on Earth in the Late-Hadean to Early-Archaean. The Late Heavy Bombardment hypothesis posits that a period of intense impact occurred at ~3.9 Gya during
8648-410: A urea solution to freeze-thaw cycles under a reductive atmosphere, with spark discharges as an energy source. The explanation given for the unusual speed of these reactions at such a low temperature is eutectic freezing , which crowds impurities in microscopic pockets of liquid within the ice, causing the molecules to collide more often. Prebiotic peptide synthesis is proposed to have occurred through
8832-410: A very similar way to the storage of information in DNA. However, RNA is less stable, being more prone to hydrolysis due to the presence of a hydroxyl group at the ribose 2' position. The major difference between RNA and DNA is the presence of a hydroxyl group at the 2'-position of the ribose sugar in RNA (illustration, right). This group makes the molecule less stable because, when not constrained in
9016-456: Is available, an explanation is needed for why the set used is so small. Formamide is attractive as a medium that potentially provided a source of amino acid derivatives from simple aldehyde and nitrile feedstocks. Alexander Butlerov showed in 1861 that the formose reaction created sugars including tetroses, pentoses, and hexoses when formaldehyde is heated under basic conditions with divalent metal ions like calcium. R. Breslow proposed that
9200-498: Is estimated that during the Late Heavy Bombardment, meteorites may have delivered up to five million tons of organic prebiotic elements to Earth per year. Polycyclic aromatic hydrocarbons (PAH) are the most common and abundant polyatomic molecules in the observable universe , and are a major store of carbon. They seem to have formed shortly after the Big Bang, and are associated with new stars and exoplanets . They are
9384-451: Is far from understood. Although Earth remains the only place where life is known, the science of astrobiology seeks evidence of life on other planets. The 2015 NASA strategy on the origin of life aimed to solve the puzzle by identifying interactions, intermediary structures and functions, energy sources, and environmental factors that contributed to the diversity, selection, and replication of evolvable macromolecular systems, and mapping
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#17327655013049568-413: Is known as the " RNA world hypothesis " of the origin of life . Since nucleotides and RNA (and thus ribozymes) can arise by inorganic chemicals, they are candidates for the first enzymes , and in fact, the first "replicators" (i.e., information-containing macro-molecules that replicate themselves). An example of a self-replicating ribozyme that ligates two substrates to generate an exact copy of itself
9752-684: 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). Since there were no known chemical pathways for
9936-405: Is not sufficient alone for peptide synthesis. Many prebiotically plausible condensing/activating agents have been identified, including the following: cyanamide, dicyanamide, dicyandiamide, diaminomaleonitrile, urea, trimetaphosphate, NaCl, CuCl 2, (Ni,Fe)S, CO, carbonyl sulfide (COS), carbon disulfide (CS 2 ) , SO 2, and diammonium phosphate (DAP). An experiment reported in 2024 used
10120-714: Is poisonous only to aerobic organisms ( eukaryotes and aerobic bacteria), which did not yet exist. It can play roles in other chemical processes such as the synthesis of the amino acid glycine. DNA and RNA components including uracil, cytosine and thymine can be synthesized under outer space conditions, using starting chemicals such as pyrimidine found in meteorites. Pyrimidine may have been formed in red giant stars or in interstellar dust and gas clouds. All four RNA-bases may be synthesized from formamide in high-energy density events like extraterrestrial impacts. Other pathways for synthesizing bases from inorganic materials have been reported. Freezing temperatures are advantageous for
10304-441: 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. Specifically, peptide bond formation, the reaction that binds amino acids together into proteins , is now known to be catalyzed by an adenine residue in
10488-399: Is that life is not required to have formed on each planet it occurs on, but rather in a more limited set of locations, or even a single location, and then spread about the galaxy to other star systems via cometary or meteorite impact. Panspermia did not get much scientific support because it was largely used to deflect the need of an answer instead of explaining observable phenomena. Although
10672-494: Is that the dual-molecule system we see today, where a nucleotide-based molecule is needed to synthesize protein, and a peptide-based (protein) molecule is needed to make nucleic acid polymers, represents the original form of life. This theory is called RNA-peptide coevolution, or the Peptide-RNA world, and offers a possible explanation for the rapid evolution of high-quality replication in RNA (since proteins are catalysts), with
10856-464: Is that the transition from non-living to living entities on Earth was not a single event, but a process of increasing complexity involving the formation of a habitable planet , the prebiotic synthesis of organic molecules, molecular self-replication , self-assembly , autocatalysis , and the emergence of cell membranes . The transition from non-life to life has never been observed experimentally, but many proposals have been made for different stages of
11040-411: Is the generation of enantioenriched glyceraldehyde, or its 3-phosphate derivative (glyceraldehyde prefers to exist as its keto tautomer dihydroxyacetone). On August 8, 2011, a report, based on NASA studies with meteorites found on Earth , was published suggesting building blocks of RNA (adenine, guanine, and related organic molecules ) may have been formed in outer space . In 2017, research using
11224-439: Is the weakest and most flexible trinucleotide among the 64 conformations, which provides the binding site for Mn . Phosphoryl transfer can also be catalyzed without metal ions. For example, pancreatic ribonuclease A and hepatitis delta virus (HDV) ribozymes can catalyze the cleavage of RNA backbone through acid-base catalysis without metal ions. Hairpin ribozyme can also catalyze the self-cleavage of RNA without metal ions, but
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#173276550130411408-416: Is to explain how such a complex and tightly interlinked system could develop by evolutionary steps, as at first sight all its parts are necessary to enable it to function. For example, a cell, whether the LUCA or in a modern organism, copies its DNA with the DNA polymerase enzyme, which is in turn produced by translating the DNA polymerase gene in the DNA. Neither the enzyme nor the DNA can be produced without
11592-450: Is unable to copy itself and its RNA products have a high mutation rate . In a subsequent study, the researchers began with the 38-6 ribozyme and applied another 14 rounds of selection to generate the '52-2' ribozyme, which compared to 38-6, was again many times more active and could begin generating detectable and functional levels of the class I ligase, although it was still limited in its fidelity and functionality in comparison to copying of
11776-465: Is universal today. That in turn implies a suite of cellular machinery including messenger RNA , transfer RNA , and ribosomes to translate the code into proteins . Those proteins included enzymes to operate its anaerobic respiration via the Wood–Ljungdahl metabolic pathway , and a DNA polymerase to replicate its genetic material. The challenge for abiogenesis (origin of life) researchers
11960-515: Is unknown. Minimum age estimates are based on evidence from the geologic rock record . The earliest physical evidence of life so far found consists of microbialites in the Nuvvuagittuq Greenstone Belt of Northern Quebec, in banded iron formation rocks at least 3.77 and possibly as old as 4.32 Gya. The micro-organisms lived within hydrothermal vent precipitates, soon after the 4.4 Gya formation of oceans during
12144-411: Is very similar to the known sexual behavior of the segmented RNA viruses, which are among the simplest organisms known. Influenza virus , whose genome consists of 8 physically separated single-stranded RNA segments, is an example of this type of virus. In segmented RNA viruses, "mating" can occur when a host cell is infected by at least two virus particles. If these viruses each contain an RNA segment with
12328-603: The Earth is 4.54 Gya as found by radiometric dating of calcium-aluminium-rich inclusions in carbonaceous chrondrite meteorites, the oldest material in the Solar System. The Hadean Earth (from its formation until 4 Gya) was at first inhospitable to any living organisms. During its formation, the Earth lost a significant part of its initial mass, and consequentially lacked the gravity to hold molecular hydrogen and
12512-409: The Earth's crust , pressure cycling leads to the periodic formation of vesicles. Under the same conditions, random peptide chains are being formed, which are being continuously selected for their ability to integrate into the vesicle membrane. A further selection of the vesicles for their stability potentially leads to the development of functional peptide structures, associated with an increase in
12696-513: The Hadean . Life consists of reproduction with (heritable) variations. NASA defines life as "a self-sustaining chemical system capable of Darwinian [i.e., biological] evolution ." Such a system is complex; the last universal common ancestor (LUCA), presumably a single-celled organism which lived some 4 billion years ago, already had hundreds of genes encoded in the DNA genetic code that
12880-619: The Isua supracrustal belt in southwestern Greenland, dating to 3.7 Gya, have shown biogenic carbon isotopes . In other parts of the Isua supracrustal belt, graphite inclusions trapped within garnet crystals are connected to the other elements of life: oxygen, nitrogen, and possibly phosphorus in the form of phosphate , providing further evidence for life 3.7 Gya. In the Pilbara region of Western Australia, compelling evidence of early life
13064-542: The Nobel Prize in chemistry for their "discovery of catalytic properties of RNA". The term ribozyme was first introduced by Kelly Kruger et al. in a paper published in Cell in 1982. It had been a firmly established belief in biology that catalysis was reserved for proteins. However, the idea of RNA catalysis is motivated in part by the old question regarding the origin of life: Which comes first, enzymes that do
13248-454: The RNA world hypothesis , which suggests that RNA may have been important in the evolution of prebiotic self-replicating systems. The most common activities of natural or in vitro evolved ribozymes are the cleavage (or ligation) of RNA and DNA and peptide bond formation. For example, the smallest ribozyme known (GUGGC-3') can aminoacylate a GCCU-3' sequence in the presence of PheAMP. Within
13432-467: The fourth most abundant chemical element in the universe (after hydrogen, helium, and oxygen ), was formed mainly in white dwarf stars , particularly those bigger than twice the mass of the sun. As these stars reached the end of their lifecycles , they ejected these heavier elements, among them carbon and oxygen, throughout the universe. These heavier elements allowed for the formation of new objects, including rocky planets and other bodies. According to
13616-402: The last universal common ancestor of all modern organisms (LUCA) is thought to have been quite different from the origin of life, investigations into LUCA can guide research into early universal characteristics. A genomics approach has sought to characterise LUCA by identifying the genes shared by Archaea and Bacteria , members of the two major branches of life (with Eukaryotes included in
13800-516: The nebular hypothesis , the formation and evolution of the Solar System began 4.6 Gya with the gravitational collapse of a small part of a giant molecular cloud . Most of the collapsing mass collected in the center, forming the Sun , while the rest flattened into a protoplanetary disk out of which the planets , moons , asteroids , and other small Solar System bodies formed. The age of
13984-430: The origins of life through the RNA world hypothesis have been working on discovering a ribozyme with the capacity to self-replicate, which would require it to have the ability to catalytically synthesize polymers of RNA. This should be able to happen in prebiotically plausible conditions with high rates of copying accuracy to prevent degradation of information but also allowing for the occurrence of occasional errors during
14168-453: The phospholipids of today. Such micro-encapsulation would allow for metabolism within the membrane and the exchange of small molecules, while retaining large biomolecules inside. Such a membrane is needed for a cell to create its own electrochemical gradient to store energy by pumping ions across the membrane. Fatty acid vesicles in conditions relevant to alkaline hydrothermal vents can be stabilized by isoprenoids which are synthesized by
14352-470: The primordial sea . PAHs and fullerenes (also implicated in the origin of life ) have been detected in nebulae . 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. Some of the difficulties of producing the precursors on earth are bypassed by another alternative or complementary theory for their origin, panspermia . It discusses
14536-569: The rRNA . RNAs are known to play roles in other cellular catalytic processes, specifically in the targeting of enzymes to specific RNA sequences. In eukaryotes, the processing of pre-mRNA and RNA editing take place at sites determined by the base pairing between the target RNA and RNA constituents of small nuclear ribonucleoproteins (snRNPs) . Such enzyme targeting is also responsible for gene down regulation through RNA interference (RNAi), where an enzyme-associated guide RNA targets specific mRNA for selective destruction. Likewise, in eukaryotes
14720-470: The ribosome , ribozymes function as part of the large subunit ribosomal RNA to link amino acids during protein synthesis . They also participate in a variety of RNA processing reactions, including RNA splicing , viral replication , and transfer RNA biosynthesis. Examples of ribozymes include the hammerhead ribozyme , the VS ribozyme , leadzyme , and the hairpin ribozyme . Researchers who are investigating
14904-405: The ribosome . The large subunit of the ribosome includes an rRNA responsible for the peptide bond-forming peptidyl transferase activity of protein synthesis. Many other ribozyme activities exist; for example, the hammerhead ribozyme performs self-cleavage and an RNA polymerase ribozyme can synthesize a short RNA strand from a primed RNA template. Among the enzymatic properties important for
15088-414: The ribosome binding site , thus inhibiting translation. In the presence of the ligand , in these cases theophylline, the regulatory RNA region is cleaved off, allowing the ribosome to bind and translate the target gene. Much of this RNA engineering work was based on rational design and previously determined RNA structures rather than directed evolution as in the above examples. More recent work has broadened
15272-471: The "soup" theory is not straightforward. Besides the necessary basic organic monomers, compounds that would have prohibited the formation of polymers were also formed in high concentration during the Miller–Urey and Joan Oró experiments. Biology uses essentially 20 amino acids for its coded protein enzymes, representing a very small subset of the structurally possible products. Since life tends to use whatever
15456-477: The 2’ hydroxyl group as a nucleophile attacking the bridging phosphate and causing 5’ oxygen of the N+1 base to act as a leaving group. In comparison, RNase A, a protein that catalyzes the same reaction, uses a coordinating histidine and lysine to act as a base to attack the phosphate backbone. Like many protein enzymes, metal binding is also critical to the function of many ribozymes. Often these interactions use both
15640-480: The 2’ position on the ribose is modified to improve RNA stability. One area of ribozyme gene therapy has been the inhibition of RNA-based viruses. A type of synthetic ribozyme directed against HIV RNA called gene shears has been developed and has entered clinical testing for HIV infection. Similarly, ribozymes have been designed to target the hepatitis C virus RNA, SARS coronavirus (SARS-CoV), Adenovirus and influenza A and B virus RNA. The ribozyme
15824-472: The Earth may have been a predominantly water world between 4.4 and 4.3 Gya. It is debated whether or not crust was exposed above this ocean due to uncertainties of what early plate tectonics looked like. For early life to have developed, it is generally thought that a land setting is required, so this question is essential to determining when in Earth's history life evolved. The post-Moon-forming impact Earth likely existed with little if any continental crust,
16008-558: The Hadean. A cataclysmic impact event would have had the potential to sterilise all life on Earth by volatilising liquid oceans and blocking the Sun needed for photosynthesising primary producers, pushing back the earliest possible emergence of life to after Late Heavy Bombardment. Recent research questions both the intensity of the Late Heavy Bombardment as well as its potential for sterilisation. Uncertainties as to whether Late Heavy Bombardment
16192-408: The Hadean. The microbes resembled modern hydrothermal vent bacteria, supporting the view that abiogenesis began in such an environment. Biogenic graphite has been found in 3.7 Gya metasedimentary rocks from southwestern Greenland and in microbial mat fossils from 3.49 Gya cherts in the Pilbara region of Western Australia . Evidence of early life in rocks from Akilia Island, near
16376-529: The Miller–Urey experiment that "it is not enough to explain the formation of such molecules, what is necessary, is a physical-chemical explanation of the origins of these molecules that suggests the presence of suitable sources and sinks for free energy." However, current scientific consensus describes the primitive atmosphere as weakly reducing or neutral, diminishing the amount and variety of amino acids that could be produced. The addition of iron and carbonate minerals, present in early oceans, however, produces
16560-584: The Moon-forming impact. This scenario has found support from the dating of 4.404 Gya zircon crystals with high δ O values from metamorphosed quartzite of Mount Narryer in Western Australia. The Hadean atmosphere has been characterized as a "gigantic, productive outdoor chemical laboratory," similar to volcanic gases today which still support some abiotic chemistry. Despite the likely increased volcanism from early plate tectonics,
16744-548: The Murchison meteorite suggest that the RNA component uracil and related molecules, including xanthine , were formed extraterrestrially. NASA studies of meteorites suggest that all four DNA nucleobases (adenine, guanine and related organic molecules) have been formed in outer space. The cosmic dust permeating the universe contains complex organics ("amorphous organic solids with a mixed aromatic – aliphatic structure") that could be created rapidly by stars. Glycolaldehyde ,
16928-705: The RNA World hypothesis nor the Peptide-RNA World theory can yet explain, unless polymerases (enzymes that rapidly assemble the RNA molecule) played a role. A research project completed in March 2015 by the Sutherland group found that a network of reactions beginning with hydrogen cyanide and hydrogen sulfide , in streams of water irradiated by UV light, could produce the chemical components of proteins and lipids, alongside those of RNA. The researchers used
17112-466: The RNA world than introns and other RNAs considered candidates at the time. Diener's hypothesis would be expanded by the research group of Ricardo Flores, and gained a broader audience when in 2014, a New York Times science writer published a popularized version of the proposal. The characteristics of viroids highlighted as consistent with an RNA world were their small size, high guanine and cytosine content, circular structure, structural periodicity,
17296-473: The RNA world. 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". The Sutherland group's 2009 paper also highlighted the possibility for the photo-sanitization of the pyrimidine-2',3'-cyclic phosphates. A potential weakness of these routes
17480-576: The Type 5 RNA boosted its polymerization ability and enabled intermolecular interactions with the RNA template substrate obviating the need to tether the template directly to the RNA sequence of the RPR, which was a limitation of earlier studies. Not only did t5(+1) not need tethering to the template, but a primer was not needed either as t5(+1) had the ability to polymerize a template in both 3' → 5' and 5' 3 → 3' directions. A highly evolved RNA polymerase ribozyme
17664-533: 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 nucleobases seen in life's nucleic acids. The nucleoside cytosine has a half-life in isolation of 19 days at 100 °C (212 °F) and 17,000 years in freezing water, which some argue is too short on the geologic time scale for accumulation. Others have questioned whether ribose and other backbone sugars could be stable enough to be found in
17848-450: The archaean branch in the two-domain system ). It appears there are 60 proteins common to all life and 355 prokaryotic genes that trace to LUCA; their functions imply that the LUCA was anaerobic with the Wood–Ljungdahl pathway , deriving energy by chemiosmosis , and maintaining its hereditary material with DNA, the genetic code , and ribosomes . Although the LUCA lived over 4 billion years ago (4 Gya ), researchers believe it
18032-424: The beginning of life are: RNA is a very similar molecule to DNA, with only two significant chemical differences (the backbone of RNA uses ribose instead of deoxyribose and its nucleobases include uracil instead of thymine ). 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
18216-405: The binding of a metabolite . Riboswitch classes have highly conserved aptamer domains, even among diverse organisms. When a target metabolite is bound to this aptamer, conformational changes occur, modulating the expression of genes carried by mRNA. These changes occur in an expression platform, located downstream from the aptamer. This change in structure can result in the formation or disruption of
18400-484: The bulk of the original inert gases. Soon after initial accretion of Earth at 4.48 Ga, its collision with Theia , a hypothesised impactor, is thought to have created the ejected debris that would eventually form the Moon. This impact would have removed the Earth's primary atmosphere, leaving behind clouds of viscous silicates and carbon dioxide. This unstable atmosphere was short-lived and condensed shortly after to form
18584-401: The bulk silicate Earth, leaving behind an atmosphere largely consisting of water vapor, nitrogen , and carbon dioxide , with smaller amounts of carbon monoxide , hydrogen, and sulfur compounds. The solution of carbon dioxide in water is thought to have made the seas slightly acidic , with a pH of about 5.5. Condensation to form liquid oceans is theorised to have occurred as early as
18768-573: The carbon-hydrogen positive ion (CH+) and the carbon ion (C+) – were produced by ultraviolet light from stars. Complex molecules, including organic molecules, form naturally both in space and on planets. Organic molecules on the early Earth could have had either terrestrial origins, with organic molecule synthesis driven by impact shocks or by other energy sources, such as ultraviolet light, redox coupling, or electrical discharges; or extraterrestrial origins ( pseudo-panspermia ), with organic molecules formed in interstellar dust clouds raining down on to
18952-436: The case of iron-sulfur chemistry. For example, this was probably important for carbon fixation . Carbon fixation by reaction of CO 2 with H 2 S via iron-sulfur chemistry is favorable, and occurs at neutral pH and 100 °C. Iron-sulfur surfaces, which are abundant near hydrothermal vents, can drive the production of small amounts of amino acids and other biomolecules. In 1961, Peter Mitchell proposed chemiosmosis as
19136-448: The chemical landscape of potential primordial informational polymers . The advent of polymers that could replicate, store genetic information, and exhibit properties subject to selection was, it suggested, most likely a critical step in the emergence of prebiotic chemical evolution. Those polymers derived, in turn, from simple organic compounds such as nucleobases , amino acids , and sugars that could have been formed by reactions in
19320-449: The chemically plausible generation of "simpler" nucleic acids under prebiotic conditions has yet to be demonstrated. In the 1980s, RNA structures capable of self-processing were discovered, with the RNA moiety of RNase P acting as its catalytic subunit. These catalytic RNAs were referred to as RNA enzymes , or ribozymes, are found in today's DNA-based life and could be examples of living fossils . Ribozymes play vital roles, such as that of
19504-488: The copying process to allow for Darwinian evolution to proceed. Attempts have been made to develop ribozymes as therapeutic agents, as enzymes which target defined RNA sequences for cleavage, as biosensors , and for applications in functional genomics and gene discovery. Before the discovery of ribozymes, enzymes —which were defined [solely] as catalytic proteins —were the only known biological catalysts . In 1967, Carl Woese , Francis Crick , and Leslie Orgel were
19688-521: The costs of redundancy. Consequently, coping with damaged RNA genes while minimizing the costs of redundancy would likely have been a fundamental problem for early protocells. A cost-benefit analysis was carried out in which the costs of maintaining redundancy were balanced against the costs of genome damage. This analysis led to the conclusion that, under a wide range of circumstances, the selected strategy would be for each protocell to be haploid, but to periodically fuse with another haploid protocell to form
19872-530: The current system might have arisen from a simpler precursor system. American molecular biologist Alexander Rich was the first to posit a coherent hypothesis on the origin of nucleotides as precursors of life. In an article he contributed to a volume issued in honor of Nobel-laureate physiologist Albert Szent-Györgyi , he explained that the primitive Earth's environment could have produced RNA molecules (polynucleotide monomers) that eventually acquired enzymatic and self-replicating functions. Other mentions of RNA as
20056-578: 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. 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. Organic chemist Donna Blackmond described this finding as "strong evidence" in favour of
20240-479: The disadvantage of having to postulate the coincident formation of two complex molecules, an enzyme (from peptides) and a RNA (from nucleotides). In this Peptide-RNA World scenario, RNA would have contained the instructions for life, while peptides (simple protein enzymes) would have accelerated key chemical reactions to carry out those instructions. The study leaves open the question of exactly how those primitive systems managed to replicate themselves — something neither
20424-466: The discovery of ribozymes that exist in living organisms, there has been interest in the study of new synthetic ribozymes made in the laboratory. For example, artificially produced self-cleaving RNAs with good enzymatic activity have been produced. Tang and Breaker isolated self-cleaving RNAs by in vitro selection of RNAs originating from random-sequence RNAs. Some of the synthetic ribozymes that were produced had novel structures, while some were similar to
20608-412: The division of the fused protocell. The cycle of haploid reproduction, with occasional fusion to a transient diploid state, followed by splitting to the haploid state, can be considered to be the sexual cycle in its most primitive form. In the absence of this sexual cycle, haploid protocells with damage in an essential RNA gene would simply die. This model for the early sexual cycle is hypothetical, but it
20792-522: The early Earth might have provided the precursor molecules necessary for self-replication. The classic 1952 Miller–Urey experiment demonstrated that most amino acids, the chemical constituents of proteins , can be synthesized from inorganic compounds under conditions intended to replicate those of the early Earth . External sources of energy may have triggered these reactions, including lightning , radiation , atmospheric entries of micro-meteorites and implosion of bubbles in sea and ocean waves. While
20976-438: The early Earth, which were very different from those that prevail today. The structure of the ribosome has been called the "smoking gun", with a central core of RNA and no amino acid side chains within 18 Å of the active site that catalyzes peptide bond formation. The concept of the RNA world was proposed in 1962 by Alexander Rich , and the term was coined by Walter Gilbert in 1986. There were initial difficulties in
21160-493: The emergence of cooperation between different RNA chains, opening the way for the formation of the first protocell . Eventually, RNA chains developed with catalytic properties that help amino acids bind together (a process called peptide-bonding ). These amino acids could then assist with RNA synthesis, giving those RNA chains that could serve as ribozymes the selective advantage. The ability to catalyze one step in protein synthesis, aminoacylation of RNA, has been demonstrated in
21344-403: The enantiomeric excess of glyceraldehyde is 60% or greater, of possible interest toward biological homochirality. 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
21528-505: The environment. A successful theory of the origin of life must explain how all these chemicals came into being. One ancient view of the origin of life, from Aristotle until the 19th century, is of spontaneous generation . This theory held that "lower" animals such as insects were generated by decaying organic substances, and that life arose by chance. This was questioned from the 17th century, in works like Thomas Browne 's Pseudodoxia Epidemica . In 1665, Robert Hooke published
21712-415: The enzyme responsible for the splicing reaction, he found that the intron could be spliced out in the absence of any added cell extract. As much as they tried, Cech and his colleagues could not identify any protein associated with the splicing reaction. After much work, Cech proposed that the intron sequence portion of the RNA could break and reform phosphodiester bonds. At about the same time, Sidney Altman,
21896-441: The evolution and preservation of polymers like RNA that store information. Only one or two types of amphiphiles have been studied which might have led to the development of vesicles. There is an enormous number of possible arrangements of lipid bilayer membranes, and those with the best reproductive characteristics would have converged toward a hypercycle reaction, a positive feedback composed of two mutual catalysts represented by
22080-513: The explanation of the abiotic synthesis of the nucleotides cytosine and uracil. Subsequent research has shown possible routes of synthesis; for example, formamide produces all four ribonucleotides and other biological molecules when warmed in the presence of various terrestrial minerals. RNA replicase can function as both code and catalyst for further RNA replication, i.e. it can be autocatalytic. Jack Szostak has shown that certain catalytic RNAs can join smaller RNA sequences together, creating
22264-492: The first drawings of a microorganism . In 1676, Antonie van Leeuwenhoek drew and described microorganisms, probably protozoa and bacteria . Van Leeuwenhoek disagreed with spontaneous generation, and by the 1680s convinced himself, using experiments ranging from sealed and open meat incubation and the close study of insect reproduction, that the theory was incorrect. In 1668 Francesco Redi showed that no maggots appeared in meat when flies were prevented from laying eggs. By
22448-511: The first molecules constituting the earliest cells slowly self-organized from a primordial soup , and this theory is called the Oparin–Haldane hypothesis . Haldane suggested that the Earth's prebiotic oceans consisted of a "hot dilute soup" in which organic compounds could have formed. J. D. Bernal showed that such mechanisms could form most of the necessary molecules for life from inorganic precursors. In 1967, he suggested three "stages":
22632-566: The first representatives of a novel domain of "subviral pathogens". Viroids infect plants, where most are pathogens, and consist of short stretches of highly complementary, circular, single-stranded and non-coding RNA without a protein coat. They are extremely small, ranging from 246 to 467 nucleobases, compared to the smallest known viruses capable of causing an infection, with genomes about 2,000 nucleobases in length. Based on their characteristic properties, in 1989 plant biologist Theodor Diener argued that viroids are more plausible living relics of
22816-417: The first to exist. Another model echoes Darwin's "warm little pond" with cycles of wetting and drying. RNA is central to the translation process. Small RNAs can catalyze all the chemical groups and information transfers required for life. RNA both expresses and maintains genetic information in modern organisms; and the chemical components of RNA are easily synthesized under the conditions that approximated
23000-464: The first to suggest that RNA could act as a catalyst. This idea was based upon the discovery that RNA can form complex secondary structures . These ribozymes were found in the intron of an RNA transcript, which removed itself from the transcript, as well as in the RNA component of the RNase P complex, which is involved in the maturation of pre- tRNAs . In 1989, Thomas R. Cech and Sidney Altman shared
23184-526: The flow from a hydrothermal vent and the surrounding seawater, or perhaps meteoric quinones that were conducive to the development of chemiosmotic energy across lipid membranes if at a terrestrial origin. The RNA world hypothesis describes an early Earth with self-replicating and catalytic RNA but no DNA or proteins. Many researchers concur that an RNA world must have preceded the DNA-based life that now dominates. However, RNA-based life may not have been
23368-609: The following generation, thus initiating the evolution of life. The lipid world theory postulates that the first self-replicating object was lipid -like. Phospholipids form lipid bilayers in water while under agitation—the same structure as in cell membranes. These molecules were not present on early Earth, but other amphiphilic long-chain molecules also form membranes. These bodies may expand by insertion of additional lipids, and may spontaneously split into two offspring of similar size and composition. Lipid bodies may have provided sheltering envelopes for information storage, allowing
23552-405: The formose reaction; the advantages and disadvantages of isoprenoids incorporated within the lipid bilayer in different microenvironments might have led to the divergence of the membranes of archaea and bacteria. Laboratory experiments have shown that vesicles can undergo an evolutionary process under pressure cycling conditions. Simulating the systemic environment in tectonic fault zones within
23736-431: The genetic code arose. Ribozyme Ribozymes ( ribo nucleic acid en zyme s) are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression , similar to the action of protein enzymes . The 1982 discovery of ribozymes demonstrated that RNA can be both genetic material (like DNA ) and a biological catalyst (like protein enzymes), and contributed to
23920-629: The greater abundance and diversity of the monomers of which they are built makes them more versatile. As some cofactors contain both nucleotide and amino-acid characteristics, it may be that amino acids, peptides, and finally proteins initially were cofactors for ribozymes. One of the challenges in studying abiogenesis is that the system of reproduction and metabolism utilized by all extant life involves three distinct types of interdependent macromolecules ( DNA , RNA , and proteins ). This suggests that life could not have arisen in its current form, which has led researchers to hypothesize mechanisms whereby
24104-407: The hot and dense centers of these protoplanetary disks formed stars by the fusion of hydrogen. Early stars were massive and short-lived, producing all the heavier elements through stellar nucleosynthesis . Element formation through stellar nucleosynthesis proceeds to its most stable element Iron- 56 . Heavier elements were formed during supernovae at the end of a stars lifecycle. Carbon , currently
24288-680: 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. On the other hand, the discovery in 2009 that activated pyrimidine ribonucleotides can be synthesized under plausible prebiotic conditions suggests that it is premature to dismiss the RNA-first scenarios. Suggestions for 'simple' pre-RNA nucleic acids have included peptide nucleic acid (PNA), threose nucleic acid (TNA) or glycol nucleic acid (GNA). Despite their structural simplicity and possession of properties comparable with RNA,
24472-435: The idea of the RNA world hypothesis conceptually plausible, though its general acceptance as an explanation for the origin of life requires further evidence. RNA is known to form efficient catalysts, and its similarity to DNA makes clear its ability to store information. Opinions differ, however, as to whether RNA constituted the first autonomous self-replicating system or was a derivative of a still-earlier system. One version of
24656-574: The improved "Round-18" polymerase ribozyme in 2001 which could catalyze RNA polymers now up to 14 nucleotides in length. Upon application of further selection on the Round-18 ribozyme, the B6.61 ribozyme was generated and was able to add up to 20 nucleotides to a primer template in 24 hours, until it decomposes by cleavage of its phosphodiester bonds. The rate at which ribozymes can polymerize an RNA sequence multiples substantially when it takes place within
24840-685: The interest in panspermia grew when the study of meteorites found traces of organic materials in them, it is currently accepted that life started locally on Earth. The idea that life originated from non-living matter in slow stages appeared in Herbert Spencer 's 1864–1867 book Principles of Biology , and in William Turner Thiselton-Dyer 's 1879 paper "On spontaneous generation and evolution". On 1 February 1871 Charles Darwin wrote about these publications to Joseph Hooker , and set out his own speculation, suggesting that
25024-453: The interstellar medium can be transformed through hydrogenation , oxygenation , and hydroxylation to more complex organic compounds used in living cells. The majority of organic compounds introduced on Earth by interstellar dust particles have helped to form complex molecules, thanks to their peculiar surface-catalytic activities. Studies of the C/ C isotopic ratios of organic compounds in
25208-410: The lack of protein-coding ability and, in some cases, ribozyme-mediated replication. One aspect critics of the hypothesis have focused on is that the exclusive hosts of all known viroids, angiosperms , did not evolve until billions of years after the RNA world was replaced, making viroids more likely to have arisen through later evolutionary mechanisms unrelated to the RNA world than to have survived via
25392-404: The ligands used in ribozyme riboswitches to include thymine pyrophosphate. Fluorescence-activated cell sorting has also been used to engineering aptazymes. Ribozymes have been proposed and developed for the treatment of disease through gene therapy . One major challenge of using RNA-based enzymes as a therapeutic is the short half-life of the catalytic RNA molecules in the body. To combat this,
25576-484: The maintenance of telomeres involves copying of an RNA template that is a constituent part of the telomerase ribonucleoprotein enzyme. Another cellular organelle, the vault , includes a ribonucleoprotein component, although the function of this organelle remains to be elucidated. Prebiotic (chemistry) Abiogenesis is the natural process by which life arises from non-living matter , such as simple organic compounds . The prevailing scientific hypothesis
25760-433: The materials for DNA and RNA to form on the early Earth . The amino acid glycine was found in material ejected from comet Wild 2 ; it had earlier been detected in meteorites. Comets are encrusted with dark material, thought to be a tar -like organic substance formed from simple carbon compounds under ionizing radiation. A rain of material from comets could have brought such complex organic molecules to Earth. It
25944-525: The mechanism for this is still unclear. Ribozyme can also catalyze the formation of peptide bond between adjacent amino acids by lowering the activation entropy. Although ribozymes are quite rare in most cells, their roles are sometimes essential to life. For example, the functional part of the ribosome , the biological machine that translates RNA into proteins, is fundamentally a ribozyme, composed of RNA tertiary structural motifs that are often coordinated to metal ions such as Mg as cofactors . In
26128-530: The mechanisms of heredity. Any successful theory of abiogenesis must explain the origins and interactions of these classes of molecules. Many approaches to abiogenesis investigate how self-replicating molecules, or their components, came into existence. Researchers generally think that current life descends from an RNA world , although other self-replicating and self-catalyzing molecules may have preceded RNA. Other approaches ( "metabolism-first" hypotheses ) focus on understanding how catalysis in chemical systems on
26312-440: The middle of the 19th century, spontaneous generation was considered disproven. Another ancient idea dating back to Anaxagoras in the 5th century BC is panspermia , the idea that life exists throughout the universe , distributed by meteoroids , asteroids , comets and planetoids . It does not attempt to explain how life originated in itself, but shifts the origin of life on Earth to another heavenly body. The advantage
26496-683: 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. 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
26680-595: The naturally occurring hammerhead ribozyme. In 2015, researchers at Northwestern University and the University of Illinois Chicago engineered a tethered ribosome that works nearly as well as the authentic cellular component that produces all the proteins and enzymes within the cell. Called Ribosome-T , or Ribo-T, the artificial ribosome was created by Michael Jewett and Alexander Mankin. The techniques used to create artificial ribozymes involve directed evolution. This approach takes advantage of RNA's dual nature as both
26864-469: The nucleotide and the unlikelihood of it spontaneously arising, along with the limited number of combinations possible among four base forms, as well as the need for RNA polymers of some length before seeing enzymatic activity, have led some to reject the RNA world hypothesis in favor of a metabolism-first hypothesis, where the chemistry underlying cellular function arose first, along with the ability to replicate and facilitate this metabolism. Another proposal
27048-629: The origin of biological monomers ; the origin of biological polymers ; and the evolution from molecules to cells. In 1952, Stanley Miller and Harold Urey carried out a chemical experiment to demonstrate how organic molecules could have formed spontaneously from inorganic precursors under prebiotic conditions like those posited by the Oparin–Haldane hypothesis. It used a highly reducing (lacking oxygen) mixture of gases— methane , ammonia , and hydrogen , as well as water vapor —to form simple organic monomers such as amino acids . Bernal said of
27232-421: The origin of life. For most of the time that followed Franklin , Watson and Crick 's elucidation of DNA structure in 1953, life was largely defined in terms of DNA and proteins: DNA and proteins seemed the dominant macromolecules in the living cell, with RNA only aiding in creating proteins from the DNA blueprint. The RNA world hypothesis places RNA at center-stage when life originated. The RNA world hypothesis
27416-439: The original genetic material, and have raised the issue that all ribose molecules would have had to be the same enantiomer , as any nucleotide of the wrong chirality acts as a chain terminator . 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
27600-508: The original spark of life may have begun in a "warm little pond, with all sorts of ammonia and phosphoric salts , light, heat, electricity, &c., present, that a proteine compound was chemically formed ready to undergo still more complex changes." Darwin went on to explain that "at the present day such matter would be instantly devoured or absorbed, which would not have been the case before living creatures were formed." Alexander Oparin in 1924 and J. B. S. Haldane in 1929 proposed that
27784-442: The other. The evolutionary process could have involved molecular self-replication , self-assembly such as of cell membranes , and autocatalysis via RNA ribozymes . Nonetheless, the transition of non-life to life has never been observed experimentally, nor has there been a satisfactory chemical explanation. The preconditions to the development of a living cell like the LUCA are clear enough, though disputed in their details:
27968-446: The phosphate backbone and the base of the nucleotide, causing drastic conformational changes. There are two mechanism classes for the cleavage of a phosphodiester backbone in the presence of metal. In the first mechanism, the internal 2’- OH group attacks the phosphorus center in a SN 2 mechanism. Metal ions promote this reaction by first coordinating the phosphate oxygen and later stabling the oxyanion. The second mechanism also follows
28152-588: The planet. An organic compound is a chemical whose molecules contain carbon. Carbon is abundant in the Sun, stars, comets, and in the atmospheres of most planets. Organic compounds are relatively common in space, formed by "factories of complex molecular synthesis" which occur in molecular clouds and circumstellar envelopes , and chemically evolve after reactions are initiated mostly by ionizing radiation . Purine and pyrimidine nucleobases including guanine , adenine , cytosine , uracil , and thymine have been found in meteorites . These could have provided
28336-483: The population, i.e., natural selection . As the fittest sets of RNA molecules expanded their numbers, novel catalytic properties added by mutation, which benefitted their persistence and expansion, could accumulate in the population. Such an autocatalytic set of ribozymes, capable of self-replication in about an hour, has been identified. It was produced by molecular competition ( in vitro evolution ) of candidate enzyme mixtures. Competition between RNA may have favored
28520-505: The possibility that the earliest life on this planet was carried here from somewhere else in the galaxy, possibly on meteorites similar to the Murchison meteorite . Sugar molecules , including ribose , have been found in meteorites . Panspermia does not invalidate the concept of an RNA world, but posits that this world or its precursors originated not on Earth but rather another, probably older, planet. The relative chemical complexity of
28704-575: The potential for self-replication. The RNA replication systems, which include two ribozymes that catalyze each other's synthesis, showed a doubling time of the product of about one hour, and were subject to natural selection under the experimental conditions. If such conditions were present on early Earth, then natural selection would favor the proliferation of such autocatalytic sets , to which further functionalities could be added. Self-assembly of RNA may occur spontaneously in hydrothermal vents. A preliminary form of tRNA could have assembled into such
28888-565: The process. The study of abiogenesis aims to determine how pre-life chemical reactions gave rise to life under conditions strikingly different from those on Earth today. It primarily uses tools from biology and chemistry , with more recent approaches attempting a synthesis of many sciences. Life functions through the specialized chemistry of carbon and water, and builds largely upon four key families of chemicals: lipids for cell membranes, carbohydrates such as sugars, amino acids for protein metabolism, and nucleic acid DNA and RNA for
29072-474: The reaction was autocatalytic in 1959. Nucleobases, such as guanine and adenine, can be synthesized from simple carbon and nitrogen sources, such as hydrogen cyanide (HCN) and ammonia. Formamide produces all four ribonucleotides when warmed with terrestrial minerals. Formamide is ubiquitous in the Universe, produced by the reaction of water and HCN. It can be concentrated by the evaporation of water. HCN
29256-461: The ribozyme synthesis of pyrimidines." This supports that NAD could have originated in the RNA world. 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, 4‘-phosphopantetheine, NMN, and FMN, respectively". Nucleotides are the fundamental molecules that combine in series to form RNA. They consist of
29440-402: The ribozyme, which would prevent infection. Despite having only four choices for each monomer unit (nucleotides), compared to 20 amino acid side chains found in proteins, ribozymes have diverse structures and mechanisms. In many cases they are able to mimic the mechanism used by their protein counterparts. For example, in self cleaving ribozyme RNAs, an in-line SN2 reaction is carried out using
29624-472: The right conditions. A similar role of increasing amino acid concentration has been suggested for clays as well. While all of these scenarios involve the condensation of amino acids, the prebiotic synthesis of peptides from simpler molecules such as CO, NH 3 and C, skipping the step of amino acid formation, is very efficient. The largest unanswered question in evolution is how simple protocells first arose and differed in reproductive contribution to
29808-461: The rock record both before and after the 3.9 Ga marker, suggesting that the early Earth was subject to continuous impacts that would not have had as great an impact on extinction as previously thought. If the Late Heavy Bombardment did not take place, this allows for the emergence of life to have taken place far before 3.9 Ga. If life evolved in the ocean at depths of more than ten meters, it would have been shielded both from late impacts and
29992-581: The same template by proteins such as the T7 RNA polymerase. An RPR called t5(+1) adds triplet nucleotides at a time instead of just one nucleotide at a time. This heterodimeric RPR can navigate secondary structures inaccessible to 24-3, including hairpins. In the initial pool of RNA variants derived only from a previously synthesized RPR known as the Z RPR, two sequences separately emerged and evolved to be mutualistically dependent on each other. The Type 1 RNA evolved to be catalytically inactive, but complexing with
30176-554: The scientists. In 2018, researchers at Georgia Institute of Technology identified three molecular candidates for the bases that might have formed an earliest version of proto-RNA: barbituric acid , melamine , and 2,4,6-triaminopyrimidine (TAP). These three molecules are simpler versions of the four bases in current RNA, which could have been present in larger amounts and could still be forward-compatible with them but may have been discarded by evolution in exchange for more optimal base pairs. Specifically, TAP can form nucleotides with
30360-565: The substrate. If a molecule possesses the desired ligase activity, a streptavidin matrix can be used to recover the active molecules. Lincoln and Joyce used in vitro evolution to develop ribozyme ligases capable of self-replication in about an hour, via the joining of pre-synthesized highly complementary oligonucleotides. Although not true catalysts, the creation of artificial self-cleaving riboswitches , termed aptazymes , has also been an active area of research. Riboswitches are regulatory RNA motifs that change their structure in response to
30544-437: The survival rate of the vesicles. Life requires a loss of entropy, or disorder, as molecules organize themselves into living matter. At the same time, the emergence of life is associated with the formation of structures beyond a certain threshold of complexity . The emergence of life with increasing order and complexity does not contradict the second law of thermodynamics, which states that overall entropy never decreases, since
30728-430: The synthesis of other RNA molecules from activated monomers under very specific conditions, these molecules being known as RNA polymerase ribozymes. The first RNA polymerase ribozyme was reported in 1996, and was capable of synthesizing RNA polymers up to 6 nucleotides in length. Mutagenesis and selection has been performed on an RNA ligase ribozyme from a large pool of random RNA sequences, resulting in isolation of
30912-495: The synthesis of purines, due to the concentrating effect for key precursors such as hydrogen cyanide. However, while adenine and guanine require freezing conditions for synthesis, cytosine and uracil may require boiling temperatures. Seven amino acids and eleven types of nucleobases formed in ice when ammonia and cyanide were left in a freezer for 25 years. S- triazines (alternative nucleobases), pyrimidines including cytosine and uracil, and adenine can be synthesized by subjecting
31096-496: The term "cyanosulfidic" to describe this network of reactions. In November 2017, a team at the Scripps Research Institute identified reactions involving the compound diamidophosphate which could have linked the chemical components into short peptide and lipid chains as well as short RNA-like chains of nucleotides. The RNA world hypothesis, if true, has important implications for the definition of life and
31280-475: The then high levels of ultraviolet radiation from the sun. Geothermically heated oceanic crust could have yielded far more organic compounds through deep hydrothermal vents than the Miller–Urey experiments indicated. The available energy is maximized at 100–150 °C, the temperatures at which hyperthermophilic bacteria and thermoacidophilic archaea live. The exact timing at which life emerged on Earth
31464-666: The three domains of life evolved. Another interesting proposal is the idea that RNA synthesis might have been driven by temperature gradients, in the process of thermosynthesis . Single nucleotides have been shown to catalyze organic reactions. Steven Benner has argued that chemical conditions on the planet Mars , such as the presence of boron , molybdenum , and oxygen , may have been better for initially producing RNA molecules than those on Earth . If so, life-suitable molecules, originating on Mars, may have later migrated to Earth via mechanisms of panspermia or similar process. The hypothesized existence of an RNA world does not exclude
31648-401: 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. Some viruses use RNA as their genetic material, rather than DNA. Further, while nucleotides were not found in experiments based on Miller-Urey experiment , their formation in prebiotically plausible conditions was reported in 2009; a purine base, adenine,
31832-421: The virus world during the RNA to DNA transition some 4 billion years ago. This finding bolsters the argument for the transfer of information from the RNA world to the emerging DNA world before the emergence of the last universal common ancestor . From the research, the diversity of this virus world is still with us. Additional evidence supporting the concept of an RNA world has resulted from research on viroids ,
32016-472: The work of the cell or nucleic acids that carry the information required to produce the enzymes? The concept of "ribonucleic acids as catalysts" circumvents this problem. RNA, in essence, can be both the chicken and the egg. In the 1980s, Thomas Cech, at the University of Colorado Boulder , was studying the excision of introns in a ribosomal RNA gene in Tetrahymena thermophila . While trying to purify
32200-411: Was able to function as a reverse transcriptase , that is, it can synthesize a DNA copy using an RNA template. Such an activity is considered to have been crucial for the transition from RNA to DNA genomes during the early history of life on earth. Reverse transcription capability could have arisen as a secondary function of an early RNA-dependent RNA polymerase ribozyme. An RNA sequence that folds into
32384-407: Was able to polymerize RNA chains longer than itself (i.e. longer than 177 nt) in magnesium ion concentrations close to physiological levels, whereas earlier RPRs required prebiotically implausible concentrations of up to 200 mM. The only factor required for it to achieve this was the presence of a very simple amino acid polymer called lysine decapeptide. The most complex RPR synthesized by that point
32568-585: Was called 24-3, which was newly capable of polymerizing the sequences of a substantial variety of nucleotide sequences and navigating through complex secondary structures of RNA substrates inaccessible to previous ribozymes. In fact, this experiment was the first to use a ribozyme to synthesize a tRNA molecule. Starting with the 24-3 ribozyme, Tjhung et al. applied another fourteen rounds of selection to obtain an RNA polymerase ribozyme by in vitro evolution termed '38-6' that has an unprecedented level of activity in copying complex RNA molecules. However, this ribozyme
32752-425: Was described in 2002. The discovery of the catalytic activity of RNA solved the "chicken and egg" paradox of the origin of life, solving the problem of origin of peptide and nucleic acid central dogma . According to this scenario, at the origin of life, all enzymatic activity and genetic information encoding was done by one molecule: RNA. Ribozymes have been produced in the laboratory that are capable of catalyzing
32936-697: Was far from the first form of life. Earlier cells might have had a leaky membrane and been powered by a naturally occurring proton gradient near a deep-sea white smoker hydrothermal vent . Earth remains the only place in the universe known to harbor life. Geochemical and fossil evidence from the Earth informs most studies of abiogenesis. The Earth was formed at 4.54 Gya, and the earliest evidence of life on Earth dates from at least 3.8 Gya from Western Australia . Some studies have suggested that fossil micro-organisms may have lived within hydrothermal vent precipitates dated 3.77 to 4.28 Gya from Quebec , soon after ocean formation 4.4 Gya during
33120-405: Was found around the protostellar binary IRAS 16293-2422 , which is located 400 light years from Earth. 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. Nitriles , key molecular precursors of the RNA World scenario, are among
33304-760: Was found in pyrite -bearing sandstone in a fossilized beach, with rounded tubular cells that oxidized sulfur by photosynthesis in the absence of oxygen. Carbon isotope ratios on graphite inclusions from the Jack Hills zircons suggest that life could have existed on Earth from 4.1 Gya. The Pilbara region of Western Australia contains the Dresser Formation with rocks 3.48 Gya, including layered structures called stromatolites . Their modern counterparts are created by photosynthetic micro-organisms including cyanobacteria . These lie within undeformed hydrothermal-sedimentary strata; their texture indicates
33488-428: Was haploid (one copy of each RNA gene) would be vulnerable to damage, since a single lesion in any RNA segment would be potentially lethal to the protocell (e.g., by blocking replication or inhibiting the function of an essential gene). Vulnerability to damage could be reduced by maintaining two or more copies of each RNA segment in each protocell, i.e., by maintaining diploidy or polyploidy. Genome redundancy would allow
33672-582: Was one giant impact or a period of greater impact rates greatly changed the implication of its destructive power. The 3.9 Ga date arises from dating of Apollo mission sample returns collected mostly near the Imbrium Basin , biasing the age of recorded impacts. Impact modelling of the lunar surface reveals that rather than a cataclysmic event at 3.9 Ga, multiple small-scale, short-lived periods of bombardment likely occurred. Terrestrial data backs this idea by showing multiple periods of ejecta in
33856-560: Was so low. However, certain sequences of base pairs have catalytic properties that lower the energy of their chain being created, enabling 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 have been proposed by some as the first, primitive forms of life. In an RNA world, different sets of RNA strands would have had different replication outputs, which would have increased or decreased their frequency in
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