RNA world hypothesis - AbsoluteAstronomy.com

The RNA world hypothesis proposes that life based on ribonucleic acid (RNA) pre-dates the current world of life based on deoxyribonucleic acid (DNA), RNA and protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s. RNA is able both to store genetic information, like DNA, and to catalyze

Catalysis

Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....

chemical reactions, like an enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

protein. It may therefore have supported pre-cellular life and been a major step in the evolution

Evolution

Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

of cellular life.

In a 2011 review of the evidence, Thomas Čech

Thomas Cech

Thomas Robert Cech is a chemist who shared the 1989 Nobel prize in chemistry with Sidney Altman, for their discovery of the catalytic properties of RNA. Cech discovered that RNA could itself cut strands of RNA, which showed that life could have started as RNA...

suggests that multiple self-replicating molecular systems probably preceded RNA. Proteins large enough to self-fold and have useful activities came about only after RNA was available to catalyze peptide

Peptide

Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

ligation

Native chemical ligation

Native chemical ligation or NCL is the most widely used form of chemical ligation, a technique for constructing a large polypeptide from two or more unprotected peptides. In native chemical ligation a peptide containing a C-terminal thioester reacts with another peptide containing an N-terminal...

or amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

polymerization

Polymerization

In polymer chemistry, polymerization is a process of reacting monomer molecules together in a chemical reaction to form three-dimensional networks or polymer chains...

, although amino acids and short peptides were present in the earlier mixtures.

Čech proposes that the RNA world evolved into a world of RNP enzymes

Ribonucleoprotein

Ribonucleoprotein is a nucleoprotein that contains RNA, i.e. it is an association that combines ribonucleic acid and protein together. A few known examples include the ribosome, the enzyme telomerase, vault ribonucleoproteins, and small nuclear RNPs , which are implicated in pre-mRNA splicing and...

, such as the ribosome

Ribosome

A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....

and ribozymes, before giving rise to the DNA, RNA and protein world

Central dogma of molecular biology

The central dogma of molecular biology was first articulated by Francis Crick in 1958 and re-stated in a Nature paper published in 1970:In other words, the process of producing proteins is irreversible: a protein cannot be used to create DNA....

of today. DNA is thought to have taken over the role of data storage due to its increased stability, while proteins, through a greater variety of monomers (amino acids), replaced RNA's role in specialized biocatalysis

Biocatalysis

Biocatalysis is the use of natural catalysts, such as protein enzymes, to perform chemical transformations on organic compounds. Both enzymes that have been more or less isolated and enzymes still residing inside living cells are employed for this task....

. The RNA world hypothesis suggests that RNA in modern cells is an evolutionary remnant of the RNA world that preceded ours. Also, many critical cofactors (ATP

Adenosine triphosphate

Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

, Acetyl-CoA

Acetyl-CoA

Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...

, NADH, etc.) are either nucleotides or substances clearly related to them.

History

The phrase "RNA World" was first used by Nobel laureate Walter Gilbert

Walter Gilbert

Walter Gilbert is an American physicist, biochemist, molecular biology pioneer, and Nobel laureate.-Biography:Gilbert was born in Boston, Massachusetts, on March 21, 1932...

in 1986, in a commentary on recent observations of the catalytic properties of various forms of RNA. However, the concept of RNA as a primordial molecule is older and can be found in papers by Crick

Francis Crick

Francis Harry Compton Crick OM FRS was an English molecular biologist, biophysicist, and neuroscientist, and most noted for being one of two co-discoverers of the structure of the DNA molecule in 1953, together with James D. Watson...

and Orgel

Leslie Orgel

Leslie Eleazer Orgel FRS was a British chemist.Born in London, England, Orgel received his B.A. in chemistry with first class honours from Oxford University in 1949...

, as well as in Woese

Carl Woese

Carl Richard Woese is an American microbiologist and physicist. Woese is famous for defining the Archaea in 1977 by phylogenetic taxonomy of 16S ribosomal RNA, a technique pioneered by Woese and which is now standard practice. He was also the originator of the RNA world hypothesis in 1977,...

's 1967 book The Genetic Code. In 1962, the molecular biologist Alexander Rich

Alexander Rich

Alexander Rich, MD is a biologist and biophysicist. He is the William Thompson Sedgwick Professor of Biophysics at MIT and Harvard Medical School. Dr. Rich earned both an A.B. and an M.D. from Harvard University. He was a post-doc of Linus Pauling along with James Watson...

, of the Massachusetts Institute of Technology

Massachusetts Institute of Technology

The Massachusetts Institute of Technology is a private research university located in Cambridge, Massachusetts. MIT has five schools and one college, containing a total of 32 academic departments, with a strong emphasis on scientific and technological education and research.Founded in 1861 in...

, had posited much the same idea in an article he contributed to a volume issued in honor of Nobel-laureate physiologist Albert Szent-Györgyi

Albert Szent-Györgyi

Albert Szent-Györgyi de Nagyrápolt was a Hungarian physiologist who won the Nobel Prize in Physiology or Medicine in 1937. He is credited with discovering vitamin C and the components and reactions of the citric acid cycle...

Properties of RNA

The properties of RNA make the idea of the RNA world hypothesis conceptually plausible, although its general acceptance as an explanation for the origin of life will require further evidence. RNA is known to form efficient catalysts and its similarity to DNA makes its ability to store information clear. Opinions vary, however, as to whether RNA comprised the ﬁrst autonomous self-replicating system or was a derivative of an earlier system. One version of the hypothesis is that a different type of nucleic acid

Nucleic acid

Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...

, 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 recent ﬁnding that activated pyrimidine

Pyrimidine

Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...

ribonucleotides can be synthesized under plausible prebiotic

Abiogenesis

Abiogenesis or biopoesis is the study of how biological life arises from inorganic matter through natural processes, and the method by which life on Earth arose...

conditions means 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 Glycerol nucleic acid (GNA). Despite their structural simplicity and possession of properties comparable with RNA, the chemically plausible generation of "simpler" nucleic acids under prebiotic conditions has yet to be demonstrated.

RNA as an enzyme

RNA enzymes

Ribozyme

A ribozyme is an RNA molecule with a well defined tertiary structure that enables it to catalyze a chemical reaction. Ribozyme means ribonucleic acid enzyme. It may also be called an RNA enzyme or catalytic RNA. Many natural ribozymes catalyze either the hydrolysis of one of their own...

, or ribozymes, are still found in today's DNA-based life and could be examples of living fossil

Living fossil

Living fossil is an informal term for any living species which appears similar to a species otherwise only known from fossils and which has no close living relatives, or a group of organisms which have long fossil records...

s. Ribozymes play vital roles, such as those in the ribosome

Ribosome

A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....

, which is vital for protein synthesis. Many other ribozyme functions exist; for example, the Hammerhead ribozyme

Hammerhead ribozyme

Hammerhead RNAs are RNAs that self-cleave via a small conserved secondary structural motif termed a hammerhead because of its shape. Most hammerhead RNAs are subsets of two classes of plant pathogenic RNAs: the satellite RNAs of RNA viruses and the viroids. The self-cleavage reactions, first...

performs self-cleavage and an RNA polymerase

RNA polymerase

RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...

ribozyme can autocatalyse

Autocatalysis

A single chemical reaction is said to have undergone autocatalysis, or be autocatalytic, if the reaction product itself is the catalyst for that reaction....

its own synthesis.

Among the enzymatic properties important for the beginning of life are:

The ability to self-duplicate, or duplicate other RNA molecules. Relatively short RNA molecules that can duplicate others have been artificially produced in the lab. The shortest was 165-bases long, though it has been estimated that only part of the molecule was crucial for this function. One version, 189-bases long, had fidelity of 98.9%, which would mean it would make an exact copy of an RNA molecule as long as itself in one of every eight copies. This 189 base pair ribozyme could polymerize a template of at most 14 nucleotides in length, which is too short for replication, but a potential lead for further investigation. The longest primer extension
Primer extension
Primer extension is a technique whereby the 5' ends of RNA or DNA can be mapped.Primer extension can be used to determine the start site of RNA transcription for a known gene. This technique requires a radiolabelled primer which is complementary to a region near the 5' end of the gene...

performed by a ribozyme polymerase was 20 bases.
The ability to catalyze
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....

simple chemical reactions which would enhance the creation of molecules which are building blocks of RNA molecules—i.e., a strand of RNA which would make creating more strands of RNA easier. Relatively short RNA molecules with such abilities have been artificially formed in the lab.
The ability to catalyse the formation of peptide bonds, in order to produce short peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

s or longer protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s. This is done in modern cells by ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....

s, a complex of several RNA molecules known as rRNA and many proteins. The rRNA molecules are thought to be responsible for its enzymatic activity, as no amino acid atoms exist within 18Å
Ångström
The angstrom or ångström, is a unit of length equal to 1/10,000,000,000 of a meter . Its symbol is the Swedish letter Å....

of the enzyme's active site
Active site
In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...

. A much shorter RNA molecule has been formed in the laboratory with the ability to form peptide bonds, and it has been suggested that rRNA has evolved from a similar molecule. It has also been suggested that amino acids may have initially been involved with RNA molecules as cofactor
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....

s enhancing or diversifying their enzymatic capabilities, before evolving to more complex peptides. Similarly, tRNA is suggested to have evolved from RNA molecules that began to catalyze amino acid transfer.

RNA in information storage

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

Comparison of DNA and RNA structure

The major difference between RNA and DNA is the presence of a hydroxyl

Hydroxyl

A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...

group at the 2'-position of the ribose

Ribose

Ribose is an organic compound with the formula C5H10O5; specifically, a monosaccharide with linear form H––4–H, which has all the hydroxyl groups on the same side in the Fischer projection....

sugar in RNA. This group makes the molecule less stable because when not constrained in a double helix, the 2' hydroxyl can chemically attack the adjacent phosphodiester bond

Phosphodiester bond

A phosphodiester bond is a group of strong covalent bonds between a phosphate group and two 5-carbon ring carbohydrates over two ester bonds. Phosphodiester bonds are central to all known life, as they make up the backbone of each helical strand of DNA...

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

Deoxyribose

Deoxyribose, more, precisely 2-deoxyribose, is a monosaccharide with idealized formula H---3-H. Its name indicates that it is a deoxy sugar, meaning that it is derived from the sugar ribose by loss of an oxygen atom...

sugar in DNA. This forces an RNA double helix to change from a B-DNA structure to one more closely resembling A-DNA

A-DNA

A-DNA is one of the many possible double helical structures of DNA. A-DNA is thought to be one of three biologically active double helical structures along with B- and Z-DNA. It is a right-handed double helix fairly similar to the more common and well-known B-DNA form, but with a shorter more...

.

RNA also uses a different set of bases than DNA—adenine

Adenine

Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...

, guanine

Guanine

Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...

, cytosine

Cytosine

Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...

and uracil

Uracil

Uracil is one of the four nucleobases in the nucleic acid of RNA that are represented by the letters A, G, C and U. The others are adenine, cytosine, and guanine. In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine.Uracil is a common and...

, instead of adenine, guanine, cytosine and thymine

Thymine

Thymine is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. As the name suggests, thymine may be derived by methylation of uracil at...

. Chemically, uracil is similar to thymine, differing only by a methyl group

Methyl group

Methyl group is a functional group derived from methane, containing one carbon atom bonded to three hydrogen atoms —CH3. The group is often abbreviated Me. Such hydrocarbon groups occur in many organic compounds. The methyl group can be found in three forms: anion, cation and radical. The anion...

, and its production requires less energy. In terms of base pairing this has no effect, adenine will readily bind uracil or thymine. Uracil is, however, one product of damage to cytosine making RNA particularly susceptible to mutations which can replace a GC base pair with a GU (wobble

Wobble base pair

In molecular biology, a wobble base pair is a non-Watson-Crick base pairing between two nucleotides in RNA molecules. The four main wobble base pairs are guanine-uracil, inosine-uracil, inosine-adenine, and inosine-cytosine . The thermodynamic stability of a wobble base pair is comparable to that...

) or AU base pair

Base pair

In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...

Limitations of information storage in RNA

The chemical properties of RNA make large RNA molecule

Molecule

A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...

s inherently fragile, and they can easily be broken down into their constituent nucleotides through hydrolysis

Hydrolysis

Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

. The aromatic bases also absorb strongly in the ultraviolet

Ultraviolet

Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...

region, and would have been susceptible to damage and breakdown by background radiation

Background radiation

Background radiation is the ionizing radiation constantly present in the natural environment of the Earth, which is emitted by natural and artificial sources.-Overview:Both Natural and human-made background radiation varies by location....

. 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.

RNA as a regulator

Riboswitches have been found to act as regulators of gene expression, particularly in bacteria, but also in plants and archaea

Archaea

The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...

. Riboswitches alter their secondary structure

Secondary structure

In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...

in response to the binding of a metabolite

Metabolite

Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

. This change in structure can result in the formation or disruption of a terminator

Terminator (genetics)

In genetics, a terminator, or transcription terminator is a section of genetic sequence that marks the end of gene or operon on genomic DNA for transcription.In prokaryotes, two classes of transcription terminators are known:...

, truncating or permitting transcription respectively. Alternatively, riboswitches may bind or occlude the Shine-dalgarno sequence

Shine-Dalgarno sequence

The Shine-Dalgarno sequence , proposed by Australian scientists John Shine and Lynn Dalgarno , is a ribosomal binding site in the mRNA, generally located 8 basepairs upstream of the start codon AUG. The Shine-Dalgarno sequence exists only in prokaryotes. The six-base consensus sequence is AGGAGG;...

, affecting translation. It has been suggested that these originated in an RNA-based world. In addition, RNA thermometer

RNA thermometer

An RNA thermometer is a temperature-sensitive non-coding RNA molecule which regulates gene expression. RNA thermometers often regulate genes required during either a heat shock or cold shock response, but have been implicated in other regulatory roles such as in pathogenicity and starvation.In...

s regulate gene expression in response to temperature changes.

Support and difficulties

The RNA world hypothesis is supported by RNA's ability to store, transmit, and duplicate genetic

Genetics

Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

information, as DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

does. RNA can also act as a ribozyme

Ribozyme

, a special type of enzyme

Enzyme

. Because it can perform the tasks of both DNA and enzymes, RNA is believed to have once been capable of supporting independent life forms. In fact, some virus

Virus

A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

es still use RNA as their genetic material, rather than DNA. Further, while nucleotide

Nucleotide

Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...

s were not found in Miller-Urey's origins of life

Abiogenesis

Abiogenesis or biopoesis is the study of how biological life arises from inorganic matter through natural processes, and the method by which life on Earth arose...

experiments, their formation in prebiotically plausible conditions has now been reported, as noted above; the purine

Purine

A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....

base known as adenine

Adenine

is merely a pentamer

Pentamer

A pentamer is a thing composed out of five sub-units.In chemistry, it applies to molecules made of five monomers.In biochemistry, it applies to macromolecules, in particular to pentameric proteins, made of five proteic sub-units....

of hydrogen cyanide. Experiments with basic ribozymes, like Bacteriophage Qβ

Bacteriophage Qβ

Bacteriophage Qβ is an icosahedral virus with a diameter of 25 nm. Its host is Escherichia coli. Qβ enters its host cell through the side of the F pilus.-Genetics:...

RNA, have shown that simple self-replicating RNA structures can withstand even strong selective pressures (e.g., opposite-chirality chain terminators).

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

Since there were no known chemical pathways for the abiogenic synthesis of nucleotides from pyrimidine

Pyrimidine

Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...

nucleobases cytosine

Cytosine

and uracil

Uracil

under prebiotic conditions, it is thought by some that nucleic acids did not contain these nucleobase

Nucleobase

Nucleobases are a group of nitrogen-based molecules that are required to form nucleotides, the basic building blocks of DNA and RNA. Nucleobases provide the molecular structure necessary for the hydrogen bonding of complementary DNA and RNA strands, and are key components in the formation of stable...

s 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 has been argued to be too short on the geologic time scale

Geologic time scale

The geologic time scale provides a system of chronologic measurement relating stratigraphy to time that is used by geologists, paleontologists and other earth scientists to describe the timing and relationships between events that have occurred during the history of the Earth...

for accumulation. Others have questioned whether ribose

Ribose

Ribose is an organic compound with the formula C5H10O5; specifically, a monosaccharide with linear form H––4–H, which has all the hydroxyl groups on the same side in the Fischer projection....

and other backbone sugars could be stable enough to be found in the original genetic material, and have raised the issue that ribose must all be the same enantiomer

Enantiomer

In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...

as any nucleotide of the wrong chirality

Chirality (chemistry)

A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....

acts as a chain terminator

Terminator (genetics)

.

Pyrimidine ribonucleosides and their respective nucleotides have been prebiotically synthesised by a sequence of reactions which by-pass the free sugars, and is assembled in a stepwise fashion by going against the dogma that nitrogenous and oxygenous chemistries should be avoided. In a series of publications, The Sutherland Group at the School of Chemistry, University of Manchester

University of Manchester

The University of Manchester is a public research university located in Manchester, United Kingdom. It is a "red brick" university and a member of the Russell Group of research-intensive British universities and the N8 Group...

have demonstrated high yielding routes to cytidine

Cytidine

Cytidine is a nucleoside molecule that is formed when cytosine is attached to a ribose ring via a β-N1-glycosidic bond...

and uridine

Uridine

Uridine is a molecule that is formed when uracil is attached to a ribose ring via a β-N1-glycosidic bond.If uracil is attached to a deoxyribose ring, it is known as a deoxyuridine....

ribonucleotides built from small 2 and 3 carbon fragments such as glycolaldehyde

Glycolaldehyde

Glycolaldehyde is the smallest possible molecule that contains both an aldehyde group and a hydroxyl group. It is the only possible diose, a 2-carbon monosaccharide, although a diose is not strictly a saccharide...

, glyceraldehyde

Glyceraldehyde

Glyceraldehyde is a triose monosaccharide with chemical formula C3H6O3. It is the simplest of all common aldoses. It is a sweet, colorless, crystalline solid that is an intermediate compound in carbohydrate metabolism...

or glyceraldehyde-3-phosphate, cyanamide

Cyanamide

Cyanamide is an organic compound with the formula CN2H2. This white solid is widely used in agriculture and the production of pharmaceuticals and other organic compounds. It is also used as an alcohol deterrent drug in Canada, Europe and Japan. The molecule features a nitrile group attached to an...

and cyanoacetylene

Cyanoacetylene

Cyanoacetylene is an organic compound with formula or H-C≡C-C≡N. It is the simplest cyanopolyyne. Cyanoacetylene has been detected by spectroscopic methods in interstellar clouds, in the coma of comet Hale–Bopp and in the atmosphere of Saturn's moon Titan....

. One of the steps in this sequence allows the isolation of enantiopure

Enantiomer

ribose aminooxazoline if the enantiomeric excess of glyceraldehyde is 60 % or greater, of possible interest towards 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 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. This was hailed as strong evidence for the RNA world. The paper also highlighted the possibility for the photo-sanitization of the pyrimidine-2',3'-cyclic phosphates. 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

Tautomer

Tautomers are isomers of organic compounds that readily interconvert by a chemical reaction called tautomerization. This reaction commonly results in the formal migration of a hydrogen atom or proton, accompanied by a switch of a single bond and adjacent double bond...

dihydroxyacetone).

On August 8, 2011, a report, based on NASA

NASA

The National Aeronautics and Space Administration is the agency of the United States government that is responsible for the nation's civilian space program and for aeronautics and aerospace research...

studies with meteorites found on Earth

Earth

Earth is the third planet from the Sun, and the densest and fifth-largest of the eight planets in the Solar System. It is also the largest of the Solar System's four terrestrial planets...

, was published suggesting building blocks of RNA

RNA

Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

(adenine

Adenine

, guanine

Guanine

and related organic molecules) may have been formed extraterrestrially in outer space

Outer space

Outer space is the void that exists between celestial bodies, including the Earth. It is not completely empty, but consists of a hard vacuum containing a low density of particles: predominantly a plasma of hydrogen and helium, as well as electromagnetic radiation, magnetic fields, and neutrinos....

Molecular biologist's dream

The molecular biologist's dream is a phrase coined by Gerald (Jerry) Joyce and Leslie Orgel

Leslie Orgel

Leslie Eleazer Orgel FRS was a British chemist.Born in London, England, Orgel received his B.A. in chemistry with first class honours from Oxford University in 1949...

to refer to the problem of emergence of self-replicating RNA

RNA

Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

molecules as any movement towards an RNA world on a properly modeled early Earth

Early Earth

The "Early Earth" is a term usually defined as Earth's first billion years, or gigayear. On the geologic time scale, the "early Earth" comprises all of the Hadean eon , as well as the Eoarchean and part of the Paleoarchean eras of the Archean eon.This period of Earth's history, being its earliest,...

would have been continuously suppressed by destructive reactions. It was noted that many of the steps needed for the nucleotides formation do not proceed efficiently in prebiotic conditions. Joyce and Orgel specifically referred the molecular biologist's dream to "a magic catalyst" that could "convert the activated nucleotides to a random ensemble of polynucleotide

Polynucleotide

A polynucleotide molecule is a biopolymer composed of 13 or more nucleotide monomers covalently bonded in a chain. DNA and RNA are examples of polynucleotides with distinct biological function. The prefix poly comes from the ancient Greek πολυς...

sequences, a subset of which had the ability to replicate".

Joyce and Orgel further argued that nucleotides cannot link unless there is some activation of the phosphate group, whereas the only effective activating groups for this are "totally implausible in any prebiotic scenario", particularly adenosine triphosphate

Adenosine triphosphate

. According to Joyce and Orgel, in case of the phosphate group activation, the basic polymer

Polymer

A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...

product would have 5',5'-pyrophosphate linkages, while the 3',5'-phosphodiester linkages, which are present in all known RNA, would be much less abundant. The associated molecules would have been also prone to addition of incorrect nucleotides or to reactions with numerous other substances likely to have been present. The RNA molecules would have been also continuously degraded by such destructive process as spontaneous hydrolysis

Hydrolysis

, present on the early Earth. Joyce and Orgel proposed to reject "the myth of a self-replicating RNA molecule that arose de novo from a soup of random polynucleotides" and hypothesised about a scenario where the prebiotic processes furnish pools of enantiopure beta-D-ribonucleosides.

Prebiotic RNA synthesis

Nucleotides are the fundamental molecules that combine in series to form RNA. They consist of a nitrogenous base attached to a sugar-phosphate backbone. RNA is made of long stretches of specific nucleotide

Nucleotide

s arranged so that their sequence of bases carries information. The RNA world hypothesis holds that in the primordial soup (or sandwich

Primordial sandwich

The concept of the primordial sandwich was proposed by the chemist Günter Wächtershäuser to describe the possible origins of the first cell membranes, and, therefore, the first cell....

), there existed free-floating nucleotides. These nucleotides regularly formed bonds with one another, which often broke because the change in energy was so low. However, certain sequences of base pairs have catalytic properties that lower the energy of their chain being created, causing them to stay together for longer periods of time. As each chain grew longer, it attracted more matching nucleotides faster, causing chains to now form faster than they were breaking down.

These chains are proposed as the first, primitive forms of life. In an RNA world, different forms of RNA compete with each other for free nucleotides and are subject to natural selection

Natural selection

Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....

. The most efficient molecules of RNA, the ones able to efficiently catalyze their own reproduction, survived and evolved, forming modern RNA. Such an RNA enzyme, capable of self replication in about an hour, has been identified. It was produced by molecular competition (in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

evolution) of candidate enzyme mixtures.

Competition between RNA may have favored the emergence of cooperation between different RNA chains, opening the way for the formation of the first proto-cell. Eventually, RNA chains randomly developed with catalytic properties that help amino acid

Amino acid

s bind together (a process called peptide-bonding

Peptide bond

This article is about the peptide link found within biological molecules, such as proteins. A similar article for synthetic molecules is being created...

). 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 a short (five-nucleotide) segment of RNA.

Further developments

Patrick Forterre has been working on a novel hypothesis: that viruses were instrumental in the transition from RNA to DNA and the evolution of Bacteria

Bacteria

Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

, Archaea

Archaea

The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...

, and Eukaryota

Eukaryote

A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

. He believes the last common ancestor

Most recent common ancestor

In genetics, the most recent common ancestor of any set of organisms is the most recent individual from which all organisms in the group are directly descended...

was RNA-based and evolved RNA viruses. Some of the viruses evolved into DNA viruses to protect their genes from attack. Through the process of viral infection into hosts the three domains of life evolved. Another interesting proposal is the idea that RNA synthesis might have been driven by temperature gradients, in the process of thermosynthesis

Thermosynthesis

Thermosynthesis is a theoretical mechanism proposed by Anthonie Muller for biological use of the free energy in a temperature gradient to drive energetically uphill anabolic reactions. It makes use of this thermal gradient, or the dissipative structure of convection in this gradient, to drive a...

.
Recently, Atul Kumar

Atul Kumar

Atul Kumar [ अतुल कुमार् ] is a scientist in the Central Drug Research Institute of Lucknow, India....

has been the first to demonstrate that single nucleotides have the ability to catalyze organic reactions. This single-nucleotide catalysis has immense impact on many fields of science such as chemistry, biochemistry, and prebiotic studies, especially the RNA world and DNA world hypothesis for understanding the origin of life on Earth.

Alternative hypotheses

As mentioned above, a different version of the same hypothesis is "Pre-RNA world", where a different nucleic acid is proposed to pre-date RNA. A candidate nucleic acid is peptide nucleic acid (PNA) which uses simple peptide bond

Peptide bond

This article is about the peptide link found within biological molecules, such as proteins. A similar article for synthetic molecules is being created...

s 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

TNA (nucleic acid)

Threose nucleic acid is a polymer similar to DNA or RNA but differing in the composition of its "backbone". TNA is not known to occur naturally; they are synthesized chemically....

) has also been proposed as a starting point, as has glycol nucleic acid (GNA

GNA (nucleic acid)

Glycol nucleic acid is a polymer similar to DNA or RNA but differing in the composition of its "backbone". GNA is not known to occur naturally; they are synthesized chemically....

), 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

PAH world hypothesis

The PAH world hypothesis is a speculative hypothesis that proposes that polycyclic aromatic hydrocarbons , assumed to be abundant in the primordial soup of the early Earth, played a major role in the origin of life by mediating the synthesis of RNA molecules, leading into the RNA world...

, whereby polycyclic aromatic hydrocarbons (PAHs) mediates the synthesis of RNA molecules. PAHs are the most common and abundant of the known polyatomic molecules in the visible Universe

Universe

The Universe is commonly defined as the totality of everything that exists, including all matter and energy, the planets, stars, galaxies, and the contents of intergalactic space. Definitions and usage vary and similar terms include the cosmos, the world and nature...

, and are a likely constituent of the primordial sea. PAHs, along with fullerenes (also implicated in the origin of life), have been recently detected in nebulae.

The iron-sulfur world theory

Iron-sulfur world theory

The iron-sulfur world theory is a set of proposals for the origin of life and the early evolution of life advanced by Günter Wächtershäuser, a Munich patent lawyer with a degree in chemistry who had been encouraged and supported by philosopher Karl R. Popper to publish his ideas. The theory...

proposes that simple metabolic processes developed before genetic materials did, and these energy-producing cycles catalyzed the production of genes.

Yet another alternative theory to the RNA world hypothesis is the panspermia hypothesis. It discusses the possibility that the earliest life on this planet was carried here from somewhere else in the galaxy, possibly on meteorites similar to the Murchison meteorite

Murchison meteorite

The Murchison meteorite is named after Murchison, Victoria, in Australia. It is one of the most studied meteorites due to its large mass , the fact that it was an observed fall, and it belongs to a group of meteorites rich in organic compounds....

. This does not invalidate the concept of an RNA world, but posits that this world was not Earth but rather another, probably older, planet.

Implications of the RNA world

The RNA world hypothesis, if true, has important implications for the definition of life.
For the majority of the time following the elucidation of the structure of DNA by Watson and Crick

Watson and Crick

James D. Watson and Francis Crick were the two co-discoverers of the structure of DNA in 1953. They used x-ray diffraction data collected by Rosalind Franklin and proposed the double helix or spiral staircase structure of the DNA molecule...

, life was considered as being largely defined in terms of DNA and proteins: DNA and proteins seemed to be the dominant macromolecules in the living cell, with RNA serving only to aid in creating proteins from the DNA blueprint.

The RNA world hypothesis places RNA at center-stage when life originated. This has been accompanied by many studies in the last ten years demonstrating important aspects of RNA function that were not previously known, and support the idea of a critical role for RNA in the functionality of life. In 2001, the RNA world hypothesis was given a boost with the deciphering of the 3-dimensional structure of the ribosome

Ribosome

A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....

, which revealed the key catalytic sites of ribosomes to be composed of RNA and for the proteins to hold no major structural role, and to be of peripheral functional importance. Specifically, the formation of the peptide bond, the reaction that binds amino acid

Amino acid

s together into protein

Protein

s, is now known to be catalyzed by an adenine

Adenine

residue in the rRNA: the ribosome is a ribozyme

Ribozyme

. This finding suggests that RNA molecules were most likely capable of generating the first proteins. Other interesting discoveries demonstrating a role for RNA beyond a simple message or transfer molecule include the importance of small nuclear ribonucleoproteins (snRNPs)

SnRNP

snRNPs , or small nuclear ribonucleoproteins, are RNA-protein complexes that combine with unmodified pre-mRNA and various other proteins to form a spliceosome, a large RNA-protein molecular complex upon which splicing of pre-mRNA occurs...

in the processing of pre-mRNA and RNA editing

RNA editing

The term RNA editing describes those molecular processes in which the information content in an RNA molecule is altered through a chemical change in the base makeup. To date, such changes have been observed in tRNA, rRNA, mRNA and microRNA molecules of eukaryotes but not prokaryotes...

and reverse transcription from RNA in Eukaryote

Eukaryote

s in the maintenance of telomeres in the telomerase

Telomerase

Telomerase is an enzyme that adds DNA sequence repeats to the 3' end of DNA strands in the telomere regions, which are found at the ends of eukaryotic chromosomes. This region of repeated nucleotide called telomeres contains non-coding DNA material and prevents constant loss of important DNA from...

reaction.

External links

"The RNA world" (2001) by Sidney Altman
Sidney Altman
Sidney Altman is a Canadian American molecular biologist, who is currently the Sterling Professor of Molecular, Cellular, and Developmental Biology and Chemistry at Yale University. In 1989 he shared the Nobel Prize in Chemistry with Thomas R...

, on the Nobel prize website
"Exploring the new RNA world" (2004) by Thomas R. Cech, on the Nobel prize website
"The Formation of the RNA World" by James P. Ferris
"Exploring Life's Origins: a Virtual Exhibit"
http://www.hhmi.org/bulletin/pdf/june2002/RNA.pdf HHMI bulletin

The source of this article is wikipedia, the free encyclopedia. The text of this article is licensed under the GFDL.

History

Properties of RNA

RNA as an enzyme

RNA in information storage

Comparison of DNA and RNA structure

Limitations of information storage in RNA

RNA as a regulator

Support and difficulties

Molecular biologist's dream

Prebiotic RNA synthesis

Further developments

Alternative hypotheses

Implications of the RNA world

See also

External links