The RNA world is an idea about a time in Earth's history when self-replicating RNA molecules were widespread before DNA and proteins evolved. This idea is also called the RNA world hypothesis. Alexander Rich first suggested this idea in 1962, and Walter Gilbert named it in 1986.
RNA has features that support its early importance. For example, RNA can store information and help create proteins.
Although other theories about how life began have been proposed, the RNA world hypothesis is the most widely accepted. Scientists agree that there is no proof yet to completely rule out other ideas. Even so, the RNA world can help researchers study how life started.
If the RNA world existed, it may have been followed by a time when ribonucleoproteins (RNP) developed. This led to the rise of DNA and longer proteins. DNA is more stable and lasts longer than RNA, which may explain why DNA became the main way life stores information. Proteins may have taken over from RNA enzymes because proteins are made from more varied building blocks, making them more useful. Some cofactors have both RNA-like and protein-like traits, so amino acids, peptides, and proteins might have first helped RNA enzymes function.
History
Studying how life began on Earth is difficult because all living things today rely on three types of large molecules—DNA, RNA, and proteins—that depend on each other to function and reproduce. This creates a problem similar to the "chicken-and-egg" question, as none of these molecules can work or copy themselves without the others. This has led scientists to search for ways the current system might have developed from a simpler system. In 1962, American scientist Alexander Rich proposed a clear idea about how nucleotides, the building blocks of RNA, could have formed on early Earth. He suggested that these molecules might have eventually gained the ability to copy themselves and perform chemical reactions.
Other scientists, including Francis Crick, Leslie Orgel, and Carl Woese, also discussed RNA as a possible early molecule in the origin of life. In 1972, Hans Kuhn described a possible process by which the modern genetic system could have developed from nucleotide-based systems. Later, in 1976, Harold White noted that many important molecules needed for enzymes (which help speed up chemical reactions) are either nucleotides or could have come from them. He proposed that early enzymes made of RNA might have used nucleotides to carry out reactions. Over time, the parts of these enzymes that were not nucleotides might have been replaced by proteins, leaving only the nucleotide parts as remnants, which he called "fossils of nucleic acid enzymes."
Properties of RNA
The properties of RNA support the idea of the RNA world hypothesis, which suggests RNA might have played a key role in the origin of life. However, more evidence is needed to confirm this theory. RNA can act as a catalyst, helping chemical reactions happen faster. It is also similar to DNA, showing it can store information like DNA does. Scientists disagree about whether RNA was the first self-replicating molecule or if another type of molecule came before it. One idea is that a different nucleic acid, called pre-RNA, might have been the first to copy itself before RNA took over. However, research in 2009 showed that certain RNA-building blocks could form under conditions similar to those on early Earth, which means the RNA-first theory still needs to be considered. Scientists have proposed simpler nucleic acids, like peptide nucleic acid (PNA), threose nucleic acid (TNA), or glycol nucleic acid (GNA), as possible early forms of RNA. These molecules are simpler in structure and have some RNA-like properties, but it is not yet proven how they could have formed under early Earth conditions.
In the 1980s, scientists discovered that RNA can act as a catalyst, a role it plays in modern life. These RNA catalysts, called ribozymes, are found in living organisms today and may be remnants of ancient systems. One important ribozyme is part of the ribosome, which helps build proteins. The ribosome’s large part includes RNA that forms bonds between amino acids during protein creation. Other ribozymes can cut RNA strands or copy RNA from a template.
RNA and DNA are very similar, but they have key differences. RNA uses a sugar called ribose, while DNA uses deoxyribose. RNA also has a base called uracil instead of thymine, which DNA uses. These small differences allow RNA and DNA to form similar double-helix structures, letting RNA store information like DNA does. However, RNA is less stable because a hydroxyl group (a group with oxygen and hydrogen) on the ribose sugar can break the RNA molecule’s backbone. This hydroxyl group also changes the shape of the RNA molecule compared to DNA, making RNA’s double helix more like a different DNA structure called A-DNA.
RNA uses the same bases as DNA—adenine, guanine, cytosine, and uracil—but replaces thymine with uracil. Uracil is easier to make than thymine, which might explain why RNA came before DNA. DNA is made from RNA building blocks by removing the hydroxyl group from ribose. This means cells must first make RNA before they can make DNA.
RNA molecules are fragile and can break down easily in water, which makes them less stable than DNA. This fragility makes RNA less efficient for storing information in modern life, where DNA is used. However, in early life, RNA might have been acceptable because it could still store information, even if it required more energy to repair or replace damaged RNA.
Riboswitches are RNA structures that help control gene activity in bacteria, plants, and archaea. They change shape when they bind to certain molecules, which can turn genes on or off. These changes happen in a part of the RNA molecule that controls gene expression. For example, riboswitches can stop or allow gene copying by changing the shape of the RNA. They can also affect how proteins are made by hiding or revealing a sequence that helps start protein production. Scientists think riboswitches might have originated in an RNA-based world. Additionally, RNA thermometers help cells respond to temperature changes by controlling gene activity.
Support and difficulties
The RNA world hypothesis suggests that RNA could have played a central role in the origin of life. RNA can store, transmit, and copy genetic information, like DNA, and can also act as an enzyme, similar to proteins. Because RNA can perform tasks now done by DNA and proteins, scientists believe it may have once supported life independently. Some viruses use RNA instead of DNA as their genetic material. While early experiments, such as the Miller-Urey experiment, did not find nucleotides, a 2009 study showed that nucleotides could form under conditions similar to those on early Earth. Adenine, a key component of ATP (a molecule used for energy in cells), is made from hydrogen cyanide. ATP is more commonly used than other similar molecules, even though others could serve the same purpose. Experiments with simple RNA structures, such as those found in the Bacteriophage Qβ virus, have shown that these structures can replicate even under challenging conditions, like the presence of molecules that stop replication.
Some scientists argue that nucleotides containing cytosine and uracil (two types of nucleobases) may not have formed naturally under early Earth conditions, as cytosine breaks down quickly when heated or over long periods of time. Others question whether ribose, a sugar in RNA, could have been stable enough to form the first genetic material. All ribose molecules would need to be the same "mirror image" (enantiomer), as incorrect ones would stop the formation of RNA chains.
Pyrimidine nucleotides (which include cytosine and uracil) can be made through chemical reactions that avoid using free sugars. In 2009, John Sutherland and his team at the University of Manchester showed that cytidine and uridine nucleotides can be built from simple molecules like glycolaldehyde, glyceraldehyde, and cyanamide. One step in this process allows for the creation of ribose with a specific mirror image, which may explain how life on Earth uses only one type of mirror image. These nucleotides can then form RNA chains. However, some challenges remain, such as ensuring the correct chemical structure of the nucleotides. Donna Blackmond, an organic chemist, called this discovery strong evidence for the RNA world hypothesis, though Sutherland noted that while nucleic acids likely played a key role in life's origin, the RNA world hypothesis may not fully explain all aspects.
In 2011, NASA research suggested that RNA building blocks, like adenine and guanine, might have formed in space and been delivered to Earth via meteorites. A 2017 study proposed that RNA could have formed in warm ponds on early Earth, with meteorites providing necessary materials. In 2012, astronomers found glycolaldehyde, a molecule needed for RNA, in a distant star system. This suggests that complex organic molecules may form in space before planets form, eventually reaching young planets. Nitriles, important for RNA, are common in space and found in meteorites, comets, and Saturn's moon Titan.
A 2001 study showed that nicotinic acid, a component of NAD (a molecule involved in energy transfer), can be made from simple molecules without enzymes. This supports the idea that NAD may have originated in the RNA world. Experiments also showed that RNA sequences of varying lengths can help create coenzymes like NAD and FAD, which are essential for cellular processes.
Prebiotic RNA synthesis
Nucleotides are the basic building blocks that link together to form RNA. Each nucleotide has a nitrogenous base connected to a sugar-phosphate structure. RNA is made up of long chains of these nucleotides, arranged so that the order of their bases carries information. The RNA world hypothesis suggests that in the early Earth environment, free nucleotides existed. These nucleotides sometimes bonded with each other, but these bonds often broke because the energy changes were small. However, some specific sequences of base pairs can lower the energy needed to form bonds, allowing these chains to remain stable longer. As these chains grew longer, they attracted more matching nucleotides more quickly, leading to faster chain formation than breakdown.
Some scientists believe these RNA chains may have been the first simple forms of life. In an RNA world, different RNA strands would replicate at different rates, changing their numbers in a population, a process similar to natural selection. As the most successful RNA strands multiplied, mutations that added helpful catalytic abilities could spread through the population. A group of RNA molecules capable of self-replication in about an hour has been identified. This group was created through molecular competition (in vitro evolution) of possible enzyme mixtures.
Competition among RNA molecules may have encouraged cooperation between different RNA strands, leading to the development of the first protocell. Over time, RNA chains gained the ability to help amino acids join together (a process called peptide bonding). These amino acids could then support RNA synthesis, giving RNA strands with catalytic abilities a survival advantage. Scientists have shown that a short RNA segment (five nucleotides long) can catalyze one step in protein synthesis, called aminoacylation of RNA.
In 2014, researchers created all four components of RNA by simulating an asteroid impact under early Earth conditions. In March 2015, NASA scientists reported that complex DNA and RNA compounds, including uracil, cytosine, and thymine, were produced in a lab using conditions found in space. These compounds were made from chemicals like pyrimidine, which may have formed in red giant stars or interstellar dust and gas. That same month, scientists produced over 50 amino acids in a lab using hydrogen sulfide, hydrogen cyanide (likely formed when meteorites reacted with atmospheric nitrogen), and ultraviolet light.
In 2018, researchers at the Georgia Institute of Technology identified three molecules—barbituric acid, melamine, and 2,4,6-triaminopyrimidine (TAP)—that may have been part of the earliest proto-RNA. These molecules are simpler versions of the four bases in modern RNA and could have been more abundant in the past. They are compatible with ribose, a sugar found in RNA. TAP and melamine can pair with barbituric acid, and all three can form nucleotides with ribose.
A 2026 study created a 45-nucleotide polymerase ribozyme from random sequences. This ribozyme can catalyze RNA synthesis using an RNA template, producing both a complementary strand and a copy of itself with reasonable accuracy. The researchers suggest that polymerase ribozymes may be more common in RNA sequences than previously believed.
Evolution of DNA
One challenge of the RNA world hypothesis is understanding how an RNA-based system changed to one based on DNA. Scientists Geoffrey Diemer and Ken Stedman from Portland State University in Oregon may have discovered a possible answer. While studying viruses in a hot, acidic lake in Lassen Volcanic National Park, California, they found evidence that a simple DNA virus had gained a gene from an unrelated RNA virus. Virologist Luis P. Villarreal from the University of California Irvine suggests that viruses capable of changing RNA genes into DNA and adding them to more complex DNA genomes may have been widespread during the transition from RNA to DNA about 4 billion years ago. This discovery supports the idea that information from the RNA world was transferred to the developing DNA world before the last universal common ancestor appeared. The research also shows that the diversity of viruses from this time still exists today.
Viroids
Additional evidence for the RNA world theory comes from studies of viroids, which are tiny, non-living particles that infect plants and are considered a new type of "subviral pathogen." Viroids consist of short, circular strands of single-stranded RNA that do not contain instructions for making proteins. They are much smaller than the smallest known viruses, which have genomes about 2,000 nucleobases long, with viroids ranging from 246 to 467 nucleobases in size.
In 1989, plant biologist Theodor Diener suggested that viroids are more likely to be ancient remnants of the RNA world than other RNA molecules, such as introns, that were considered at the time. This idea was later expanded by the research group of Ricardo Flores. In 2014, a science writer from The New York Times shared a simplified version of this theory with a wider audience.
Viroids are considered similar to the RNA world because of their small size, high amounts of guanine and cytosine, circular shape, repeating patterns in their structure, lack of protein-coding ability, and in some cases, the ability to replicate using ribozymes. However, critics argue that all known viroids only infect angiosperms, a type of plant that evolved billions of years after the RNA world ended. This timing makes it more likely that viroids developed later through unrelated evolutionary processes rather than surviving from the RNA world. Regardless, their ability to function as self-replicating RNA molecules is seen as similar to what scientists imagine for the RNA world.
Origin of sexual reproduction
Scientists named Eigen and others, along with Woese, suggested that the first simple life forms, called protocells, had genomes made of single-stranded RNA. In these early protocells, each gene was a separate piece of RNA, not connected together like the DNA in modern cells. A protocell with only one copy of each RNA gene (called haploid) would be at risk of harm. If any single RNA piece was damaged, it could stop the protocell from copying itself or stop an important gene from working, which could kill the protocell.
To reduce the risk of damage, protocells might have kept multiple copies of each RNA piece, a state called diploidy or polyploidy. Having extra copies would allow a damaged RNA piece to be replaced by another copy. However, keeping many copies of RNA would use a large amount of the protocell’s resources. If resources were limited, protocells with more copies might reproduce more slowly. The cost of keeping extra copies could lower the protocell’s overall health. Therefore, early protocells likely faced a challenge: dealing with damaged RNA while using resources efficiently.
A study compared the costs of keeping extra RNA copies with the costs of damage. The results suggested that the best strategy might be for protocells to stay haploid most of the time but occasionally join with another haploid protocell to form a temporary diploid state. Staying haploid allows the protocell to grow quickly. The temporary diploid state lets damaged protocells repair themselves if at least one undamaged copy of each RNA gene is present. To create two new protocells instead of one, the undamaged RNA copy must be copied again. This cycle of haploid reproduction, with occasional temporary diploid fusion, could be the earliest form of a sexual cycle. Without this cycle, a haploid protocell with a damaged essential RNA gene would not survive.
This model is a hypothesis, but it closely matches the reproductive behavior of segmented RNA viruses, which are among the simplest living things. For example, the influenza virus has a genome made of 8 separate single-stranded RNA pieces. These viruses can "mate" when a cell is infected by at least two virus particles. If each virus has a damaged RNA piece, the infection can still produce new viruses if the cell has at least one undamaged copy of each RNA gene. This process is called "multiplicity reactivation" and has been observed in influenza infections after damage caused by UV light or radiation.
Further developments
Patrick Forterre has proposed a new idea called "three viruses, three domains." This idea suggests that viruses played an important role in the change from RNA to DNA and the development of Bacteria, Archaea, and Eukaryota. He believes the last universal common ancestor was based on RNA and had RNA viruses. Some of these viruses changed into DNA viruses to better protect their genetic material. Over time, viruses infected hosts, which helped lead to the three major groups of living things.
Another idea is that RNA molecules may have formed because of temperature differences through a process called thermosynthesis. Scientists have found that single nucleotides can help speed up chemical reactions.
Steven Benner has suggested that Mars may have had better chemical conditions for creating RNA molecules than Earth. These conditions include the presence of boron, molybdenum, and oxygen. If true, life-related molecules that formed on Mars might have later traveled to Earth through processes like panspermia.
Alternative hypotheses
Scientists suggest that an RNA world may not be the first stage of life. Instead, a "Pre-RNA world" is proposed, where a different type of nucleic acid, such as peptide nucleic acid (PNA), might have existed before RNA. PNA uses simple peptide bonds to connect nucleobases, which are building blocks of genetic material.
Another idea, called the PAH world hypothesis, suggests that polycyclic aromatic hydrocarbons (PAHs)—common molecules found in space—helped create RNA. PAHs are widespread in the universe and may have been part of Earth’s early environment. These molecules, along with fullerenes (also linked to life’s origins), have been found in space, such as in nebulae.
Some challenges in forming life’s building blocks on Earth are addressed by the theory of panspermia. This idea proposes that life’s earliest forms may have arrived on Earth from elsewhere in the galaxy, possibly via meteorites like the Murchison meteorite. Scientists have found sugar molecules, including ribose, in such meteorites.
Another theory suggests that the modern system, where nucleic acids and proteins depend on each other, may have been the original form of life. This is called the RNA-peptide coevolution theory or the Peptide-RNA world. It explains how proteins, which act as catalysts, could speed up RNA replication. However, this theory requires explaining how both RNA and proteins formed together, which remains a challenge. Neither the RNA world nor the Peptide-RNA world theories fully explain how early systems replicated themselves, unless enzymes called polymerases played a role.
In March 2015, a study by the Sutherland group showed that reactions involving hydrogen cyanide and hydrogen sulfide in water exposed to UV light could produce components of proteins, lipids, and RNA. These reactions were named "cyanosulfidic." In November 2017, researchers at the Scripps Research Institute found that diamidophosphate could link these components into short peptide, lipid, and RNA-like chains.
Implications
The RNA world hypothesis, if correct, changes how scientists understand what life is and how life began. For many years after James Watson and Francis Crick discovered the structure of DNA in 1953, life was mostly described using DNA and proteins. These molecules were seen as the main parts of living cells, while RNA was thought to only help in making proteins based on DNA instructions.
The RNA world hypothesis suggests that RNA played a central role in the beginning of life. This idea is supported by evidence that ribosomes, which help build proteins, are made partly of RNA. The part of the ribosome that performs chemical reactions is made of RNA, and proteins are not a major part of its structure. This was confirmed in 2001 when scientists studied the 3D shape of the ribosome. Specifically, the process of linking amino acids to form proteins is now known to be done by a part of the ribosomal RNA called adenine.
RNA is also involved in other important processes in cells. For example, it helps direct enzymes to specific RNA sequences. In eukaryotic cells, the processing of pre-mRNA and RNA editing occur at locations determined by how RNA interacts with small nuclear ribonucleoproteins (snRNPs). RNA also helps control gene activity through a process called RNA interference (RNAi), where a guide RNA helps enzymes destroy specific messenger RNA molecules. In eukaryotes, the ends of chromosomes called telomeres are maintained by copying an RNA template that is part of the telomerase enzyme. Another cell structure, the vault, contains a ribonucleoprotein component, though its exact function is still unknown.