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.
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.
This is very nice. One thing it made me wonder is about how things keep going when only every second RNA chain reproduces the original. Do the odd-numbered generations do anything except randomly survive to give rise to another even-numbered generation with the function of the original (with small variations)? Or do their mirror structures have some relation to the structures of the even-numbered generations? Do structures that have a more robust "between generations" structure have a survival advantage over RNA sequences that are more vulnerable in their mirror states?
ReplyDeleteIn most cases, a ribozymes compliment structure won't have any enzymatic function, at least not fine tuned.
DeleteYou are correct in assuming there will be selection on the complement though too. Probably conflicting selection in many cases. So far as I know, in the experiments done so far, conflicting selection has not been measured.
Are there scientific papers published on this or is it just coming together now? I see many assumptions that must somehow be explained, as you admitted in the end of this blog. I'm pretty skeptical on this info.
ReplyDeleteThe RNA world hypothesis is certainly a work in progress but there is extensive literature on it and continual breakthroughs encouraging more and more scientists to work within the paradigm.
DeleteFor info on Ribozymes with links to papers, wikipedia actually has a great current article: https://en.wikipedia.org/wiki/Ribozyme
For an overview of problems in the RNA world, here's a good journal article (it's a few years old, keep in mind that problems number 2, 6, 7, and 8 mentioned there have since been solved): http://jsystchem.springeropen.com/articles/10.1186/1759-2208-3-2
Here's a paper on in vitro evolution of a nucleotide building ribozyme (super cool!) http://www.sfu.ca/~punrau/pdfs/Lau_JACS_2004.pdf
Here's an article on an alternative to the RNA world. It's about the work being done at Nick Hud's lab on a pre-RNA that might replicate and evolve easier than RNA to get things started. Currently the system is having issues with backbone formation but if they can solve that, it looks super promising: http://www.sciencemag.org/news/2013/02/self-assembling-molecules-offer-new-clues-lifes-possible-origin
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