Published AUGUST 2016

What Is the RNA World Hypothesis?


All living creatures today reproduce and evolve using a complex gene-enzyme cycle. If we look at a cell, for example, information encoded in its genes is used to produce functional proteins called enzymes. Some of those enzymes then turn around to make copies of the cell's genes, allowing the cell to reproduce. 

Because the gene-enzyme system forms a closed loop, it presents us with a classic chicken or egg conundrum: Which came first, genes or the protein enzymes they code for? 

While the details are still not fully worked out, discoveries over the past few decades have lead researchers to a surprising possible solution: What really came first? Genes that act as enzymes!

The RNA World Hypothesis is the idea that before living cells, the genetic code, and the gene/protein cycle ever existed, chains of a chemical called RNA were forming naturally. Once formed, some of these chains were able to function as enzymes, and were even able to evolve by making copies of themselves with slight, accidental modifications.

In the purest form of RNA World Hypothesis, RNA came first and then gave rise to proteins and DNA. This pure form is not largely accepted. It now seems more likely that RNA, DNA, small proto-proteins, and even lipids all coexisted from the start. 

While there is little doubt that RNA played a crucial role in the early development of life, the complexity of RNA and DNA nucleotides cast doubt on the idea that RNA was the first truly replicating and evolving chemical system. For this reason, alternatives to the “RNA first” view are being investigated. Most notable is a proto-RNA hypothesis being studied by the lab of Nicholas Hud, and several metabolism first hypotheses which got their start with the work of Robert Shapiro.

At this time, all serious investigations into the origin of life are being done under the overarching idea that life emerged from chemistry.


The first RNA enzymes were discovered in 1982, now known as ribozymes. Here’s is a wonderful review of what we now know about ribozymes (well... as of 2002): 

Scientific Paper: Ribozymes: Catalytic RNAs that cut things, make things, and do odd and useful jobs 

Diverse and highly functional ribozymes can be evolved in the lab. Selection experiments have shown there are many pathways that evolution can take to produce a ribozyme with a given function. This means the evolution of function is much simpler than previously thought! 

Scientific Paper: Next-generation sequencing reveals how RNA catalysts evolve from random space

Nucleotide building ribozymes have been evolved in the lab from random starting chains (this is the experiment discussed in our animation):

Scientific Paper: Isolation of Fast Purine Nucleotide Synthase Ribozymes

RNA nucleotides are not easy to make but they have been shown to form without enzymes under conditions that might have been plausible on the early Earth. That said, the reactions we’ve discovered so far do not appear robust enough to have initiated the RNA world. A search for a more efficient natural pathway continues. 

Scientific Paper: Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions

News Article discussing the paper above: Ingenious chemistry shows how nucleotides may have formed in the primordial soup.

In order for ribozymes to develop and evolve, they must be able to reproduce. Base pairing allows us to get RNA to easily replicate in the lab but there are several issues impeding replication in natural environments like those that would have existed on the early Earth. Below is a paper outling 8 problems with RNA replication and likely solutions to them (note: number 8 has since been solved by two different research groups independently though one is still waiting to be published): 

Scientific Paper: The eightfold path to non-enzymatic RNA replication

RNA certainly played an important early role in life but the difficulties of producing RNA under pre-biotic conditions raises doubts about RNA chains truely being the first replicators.

Article conrasting several ideas about life origins, including the metabolism first hypothesis: by professor Laurance Moran: Metabolism First and the Origin of Life 

Media article reviewing research into a possible proto RNA World Hypothesis: Chemists Seek Possible Precursor to RNA