Published AUGUST 2016

What Is the RNA World Hypothesis?


If you were to go back in time 120 million years, you’d find yourself in a Dinosaur World, 500 million years ago was a world of trilobites and other strange sea creatures, 3.4 billion years ago was the world of the first living cells, and if you were to go back further still, scientists suspect that chains of a chemical called RNA, or something similar to RNA, kickstarted this entire beautiful mess that we call life.

RNA is thought to have given rise to life for several reason: chains of RNA are found abundantly in all living cells today, RNA is a close chemical cousins to DNA, and with very little help from researchers, RNA chains can replicate, evolve, and interact with their environments. 

While many details have yet to be worked out, the RNA world hypothesis is the simple idea that somewhere on our early planet, perhaps in a tide pool or hot spring, the Earth’s chemistry was producing random chains of RNA. Once formed, they began replicating, evolving, and competing with each other for survival.

As these chains evolved and diversified, some eventually began cooperating to produce the genetic code, a wide array of complex proteins, and even living cells which from the perspective of RNA can actually be thought of as houses or “survival machines” for RNA to live inside.

To understand how RNA chains can interact with their environments, replicate, and evolve; we first need to understand the simple process of base pairing.

Chains of RNA are made of nucleotides — small molecules that come in 4 different types labeled A,C,U and G.

The backbone atoms of a nucleotide (shown here as a yellow bar) can form strong chemical bonds with the backbone atoms of any other RNA nucleotide. This means that different chains can have completely different sequences from left to right.

The parts we call the bases of nucleotides (the colored sections labeled A, C, U, or G) are attracted to other bases, sort of like a magnet, but they’re selective about who they will stick to: G selectively pairs with C, A selectively pairs with U.

When bases find their matches and stick together, we call it base pairing. Researchers have found that with a little bit of assistance, base pairing allows chains of RNA to replicate and evolve. Here’s how it works:

When a long chain of RNA is suspended in cool water with high concentrations of free nucleotides, the chain can act as a template for its own replication. Nucleotides automatically base pair with their partners on the existing chain. If their backbone atoms form chemical bonds with each other (by the way, this is the part that currently requires assistance from researchers, we’re not yet sure how this would have happened in the wild) a complementary RNA strand is born—one with the exact inverse sequence of the original. If the water is then heated, paired bases lose their grip, allowing both chains to act as templates when the cycle repeats.

The great thing about this process is that every other RNA chain produced, is a copy of the original but sometimes mutations slip in. This means that as chains compete for survival and reproduction, true evolution - descent with modification, acted upon by selection - can operate on chains of RNA.

As amazing as replication is, base pairing also gives RNA chains a second special ability.

When placed in water cool enough for base pairing but without enough free nucleotides for replication, chains will fold up and base pair with themselves. The end result is a complex shape with certain sticky bases pointing outward because they weren’t able to find partners. These sticky outward facing bases can cause unique chemical reactions, by interacting with other molecules in their environment.

A folded chain of RNA capable of guiding a specific chemical reaction is what we call a ribozyme. Some ribozymes break certain molecules apart, others join certain molecules together. A ribozyme’s specific function is determined by its specific shape, and its shape is determined by its sequence. If a mutation changes a ribozyme’s sequence, the shape can be modified and so can its function.

When ribozymes were first discovered scientists wondered how difficult it would be for random chains of RNA to evolve legitimate survival functions. Imagine, for example, a ribozyme that could build nucleotides out of molecules it finds in its environment. Across multiple generations, natural selection could promote and refine this ribozyme because the chain would tend to have access to more free nucleotides than its rivals, allowing it to replicate more often.

To explore this idea, researchers at Simon Fraser University produced a large group of random RNA chains, and examined them to see if any happened to be able to make nucleotides. Surprisingly, some actually could, but they weren’t very efficient.

Researchers selected out the successful chains and then used a lab technique called PCR to quickly replicate them with slight random mutations. After just 10 rounds of PCR followed by selection, highly efficient nucleotide building ribozymes evolved — these are molecules with the life-like ability to actively participate in their own survival!

These ribozymes, and many others produced through similar experiments, are beginning to blur the line between living things and simple chemistry.

So to sum things up, the RNA world hypothesis is the simple idea that the first things to replicate and evolve on our planet may have been chains of RNA, or something similar to them.

While the basic idea of the RNA world does seem to give us a promising pathway to the origin of life, it’s still very much a work in progress. As mentioned, one of several unsolved problems is how did nature get backbone binding to function without the special enzymes or the lab techniques we use today?

While many researchers continue to focus on RNA, others are investigating alternative molecules — chemical systems that might replicate and evolve without assistance, and could have given rise to RNA. Continual breakthroughs are being found in both avenues of research.