Second draft of the RNA World Script

Here I have an updated version of the RNA world script. It flows better than the last one and is easier for new people to follow:

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 before that, scientists suspect that chains of a chemical called RNA, or something similar to RNA, kickstarted this entire beautiful mess 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, they’re 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 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 part currently requires assistance from researchers) a complementary RNA strand is born—one with the exact inverse sequence of the original. If the water is then heated, paired bases release their grip, freeing 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. Motivated by curiosity, 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 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 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.

What is the RNA world hypothesis?

This is a draft script for my upcoming animation on the RNA world. Please comment below, I will read and consider your ideas for improvement. By the way, this is intended to be a voice-over with animation. I promise it will be way easier to follow once moving graphics accompany the text :) All living creatures today (even viruses which some people don’t consider to be alive) reproduce and evolve using a gene-protein 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 protein enzymes then turn around to make copies of the cell's genes, allowing it to reproduce. 

An enzyme, by the way, is a molecule capable of directing specific chemical reactions. Different enzymes do different things. One might specialize in breaking down sugar for example, another might construct the building blocks of the cell wall. An enzyme's distinct function is determined by its 3 dimensional shape and its polar charge.

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

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

When the study of genetics kicked off big in the 1950s, it was initially assumed that genes could only do one thing: carry information about how cells should build proteins. Information carrying genes could be made out of DNA, or it’s close chemical cousin, RNA. 

In the early 1980s, research teams lead by two scientists, Sidney Altman and Thomas Cech, independently discovered stretches of RNA that were not carrying information about how to build proteins. Instead, when conditions were right, the RNA chains would fold into complex 3 dimensional shapes, becoming functional enzymes themselves! No protein needed! 

Because these enzymes are made of RNA (ribonucleic acid) today we call them ribozymes.

The RNA world hypothesis is the idea that before the genetic code and the gene/protein cycle ever existed, RNA chains were forming naturally. Once formed, some of these strands happened to be able to function as ribozymes, and were even able to evolve by making copies of themselves with slight accidental variations.  

To understand how RNA chains could capable of replication and evolution, and to see how they can fold in on themselves to form ribozymes, we first need to understand how base pairing works.

An RNA chain is made of nucleotides, small molecules that come in 4 different types labeled A,C,U and G. 

The backbone of a nucleotide (shown here in yellow) can form a really strong bond with the backbone of any other nucleotide. This means the letter sequence of a chain from left to right can be random. Different RNA chains can have completely different sequences. The part we call the base of a nucleotide (the colored parts labeled either A, C, U, or G) are attracted to other bases, sort of like magnets, but they’re selective about who they want to stick to: As only stick to Us, Cs only stick to Gs.

When basses find their matches and stick together, we call it base pairing. 

When an RNA chain is suspended in water with drifting nucleotides, the chain acts as a template for its own replication. Drifters will base pair with their partners on the parent chain and if the backbones of the newly attached nucleotides are then permitted to bind (which, by the way, easier said than done), a complementary RNA strand is born, one with the the exact opposite sequence of the parent chain. Temperature changes in the water can cause the two chains can separate, both acting as templates as the cycle repeats.  

The great thing about this is that every other RNA chain born is a copy of the original, but with slight, or sometimes major variations due to random copying errors. This means that true Darwinian evolution - descent with modification, acted upon by selection - can operate on RNA chains.

When suspended in water, without free floating nucleotides, the attraction between bases will cause an RNA chain to bend in on itself and stick together in certain areas as base pairs form. The end result is a complex 3 dimensional shape. Depending on that shape, it might not really do anything of interest but it might act as a weak ribozyme for a given function, it might act as strong ribozyme! 

The important thing to realize here is that the sequence of nucleotides in the RNA chain determine what kind of 3 dimensional shape and function the chain will have once folded. Any change in sequence can result in a change of the 3 dimensional shape. Changes in shape can change a ribozyme’s function.

This means that as RNA chains reproduce with modifications, natural selection can work, promoting ribozymes that happen to have survival functions, and even refining their abilities as generations pass. 

By setting up conditions allowing random RNA chains to evolve in the lab, scientists have directly observed the emergence of many powerful, finely tuned ribozymes! 

From these experiments, researchers speculate that under the right conditions, communities of evolving ribozymes could eventually give rise to living cells. 

So to sum things up, What is the RNA world hypothesis?

The RNA world hypothesis is the idea that self-replicating RNA chains were somehow produced on the early Earth. Through descent with modification, acted upon by selection, these early molecules evolved into a diversity of functional ribozymes, and eventually giving rise to living cells. 

While the basic idea of the RNA world hypothesis looks extremely promising, scientists still have many questions about the details. We don’t know for sure what pathways nature could have taken to turn simple chemistry into RNA chains. Once those first chains were formed what kinds of natural environments could have facilitated their reproduction and evolution? RNA evolution works great in a sterile lab, but could anything interesting happen in a puddle or a tidepool? 

Slowly but surely, answers to these questions and many others are being discovered by curious minds around the globe.