Ep 2 - The Workers Arrive

RNA can store information—but it can’t do everything alone.

In this episode, we explore how amino acids entered the picture and why life needed molecular “workers” to survive and evolve.

Transcript

Jackie 0:03

Hello, I'm your host Jackie Mullins and welcome to From Cells To Us, how the podcast where we figure out how life went from a single cell to complex creatures like us. I told you last episode, I would tell you which hypothesis I thought was correct for our origin of life. Well, my answer is both. So it wasn't an either or situation. It was all the above. Both the above Earth got ingredients from multiple sources, and chemistry did what? Chemistry does. More ingredients meant more chances to stumble onto self-replicating molecules. Now, this is actually most likely what happened. Life got help from both earth and space, so it was a team effort. The idea that both earth-based chemistry and space delivered molecules contributed to life is actually the mainstream scientific view as we have good evidence for both. Now, let's do a quick recap of episode one. Earth started as a molten ball of liquid, hot magma. 4.5 billion years ago. No land was able to be formed. Carbon bonded with everything, and that formed organic molecules. RNA became the wonder molecule. Storing information. Catalyzing reactions and copying itself. Think of that lone tuba player. Fatty acid membranes like little spherical Oreos, spontaneously formed bubbles and accidentally trapped RNA inside. Boom. Protocells. All four boxes checked, protection instructions, fuel reproduction, those protocells could divide and evolve. RNA was king, but RNA was fragile and limited. Something had to change and all kings must fall. So last episode, we went basically. From dust to life. This episode, we're taking the next crucial step because if things continued with only RNA in charge, we would not have gotten as far as we did. No plants, no animals, no us. So we left off with life created, RNA, trapped in a bubble, dividing and evolving. Boom, you know, we did it. But here's the thing that RNA, that started life. Well, it's about to realize it can't do it all by itself. It can't do it alone. At this point, RNA is like that mom of eight kids who swears she's fine as she's doing everything and has like giant bags under her eyes. Hasn't taken a shower in two weeks like she needs. She needs help someone give this poor woman some help. Side note, she's a single mom in this situation. I'm certain if she had any upstanding people listening like you, she wouldn't have the same problems. So RNA had no supporting molecules, no systems. Early life had no workhorses. So RNA put the team on his back, much like Craig Jennings and Madden, RNA is checking off three of four boxes to make a cell copy yourself, catalyze reactions and store information. It's got a lot on its shoulders. So RNA is just doing it all, but it's not great at all of its jobs. It's the jack of all trades, master of none. Also, RNA is super fragile. It breaks down very easily. Unlike Greg Jennings, it's like, here you go. The secret to starting life is right here on this tissue paper. Enjoy keeping that alive. For life to continue or at least get more complex RNA needed help. And here's the beautiful part. The help was already there. It had been there all along. Actually, we just haven't been able to talk about it yet. It's like when Elizabeth Banks joined Scrubs in like the fourth season or something and they claimed she was there the whole time and just inserted her in past times, which was hilarious. That's where this help was. It just wasn't noticed. So remember way back in episode one when I told you about the Miller Yuri experiment, the one from 1952, where they basically bottled up a had on eon in a lab. And simulated early earth conditions. Well, I told you that they made organic molecules, but what I didn't tell you is what organic molecules that they made, they made amino acids and not just one or two. They made several different kinds just by running electricity, simulating lightning through a mixture of simple gases, methane, ammonia, hydrogen, and water. Boom, amino acids. So amino acids have been around since the beginning. They were just floating in those primorial seas right alongside RNA. They were in the same warm little ponds, the same tidal pools, the same hydrothermal vents So when the fatty acid vesicles formed those little Oreo bubbles that trapped RNA, well, they also trapped whatever small molecules happened to be nearby. And in most cases, that meant they trapped amino acids. Also, this first membrane wasn't exactly Fort NOx. Lots of things just popped right through including amino acids. So even if amino acids weren't trapped right away, they could just pop in. So RNA wasn't completely alone in that bubble. It just took a while for RNA to figure out what to do with those roommates. Okay, so what the heck is an amino acid? And amino acid is a pretty simple organic molecule. And remember, organic just means it has carbon in it. Picture it like this. You've got a carbon atom in the middle, and that's your anchor point and attached to that carbon you have an amino group, a acid group, and a hydrogen atom, blah, blah, blah. And then one more piece, a side chain, and this is what makes each amino acid different. It's kind of like. Mr. Potato Head, the basic body is always the same. That's the carbon anchor with the amino group and an acid group and the hydrogen, but the accessories that you stick on, that's the side chain. That's their bling bling, and depending on which accessory you use, you get a completely different personality. So some amino acids have tiny side chains like glycine, which is basically just a hydrogen atom. Super simple, super flexible, like a, a normal small tasteful silver chain. Some have big, bulky side chains like trytophan. Which has these ring structures that take up space. That'd be like the football player wearing the necklace as big as his shoulder pads. Well, these side chains, they all like different things. Some love water, some hate it. Some are positively charged, some are negatively charged, some are neutral. There are 20 standard amino acids that life uses, 20 different Mr. Potato head configurations, 20 different personalities. So why do we care? Why does this matter? Well, so far this ancient cell has been running on R-N-A-R-N-A has four bases, four building blocks to work with A UGC. That's it. Amino acids have 20. It's like RNA walked into first grade with the four pack of crayons, you know, just your primary colors. Well, and another one because there's only three primary colors. Then amino acid wats in takes out the ever sought after 64 pack of Crayola crayons with the sharpener on the back. So amino acids are just bobbing around in early life with a crazy amount of potential, just haven't been put to work yet. It's kinda like RNA would be the super hardworking sibling that the parents take for granted. And amino acids are the younger siblings who can still do things, but the parents are like, no, they're so cute and little. But the big sibling, RNA is about to put an end to that. So let's pause for a second and make sure we got this. Amino acids were made in the Miller Uri experiment. They've been around since the beginning. They were floating around inside and outside of the protocells, small enough to pass through these leaky membranes. An amino acid has an amino group, an acid group, and a side chain with a carbon anchor. The MR. Potato head accessory. There are 20 different standard amino acids each with different properties based on their side chain. RNA has four bases. Amino acids come in, 20 varieties. So amino acids were floating around in this primordial soup and inside the proto cells with RNA. Cool. But so what? Lots of things were floating around, what made amino acids so special? Well, to understand that we need to first understand what RNA was actually doing inside those bubbles. I've said a few times that RNA was doing chemistry or catalyzing reactions, but what does that actually mean? Were these molecules using beakers? Titrating things, making that little white magnetic pill spin? No. What I mean when I say doing chemistry is this, RNA was acting like a tool. In the best way. You know how a hammer has a specific shape that lets it hit nails? RNA, that folded the right way, became a molecular tool, its shape. Let it grab onto other molecules and do something to'em. Cut them, stick'em together. Speed up a reaction. That would other ways take forever. Think of it like this. Imagine you've got two magnets and they're sitting on a table. They could snap together eventually, maybe in a million years when random vibrations happen enough to push them together just right. Or you could use your hands and push them together in two seconds. That's what RNA was doing. Being the hands that helped molecules connect way faster than they could on their own, but here's the key question. How does a simple string of RNA become a useful tool? And the answer is folding. It couldn't help Itself. It's kinda like that yo-yo string, you know when it's all twisted and you don't pull it too taut and it twists up on itself. That's how RNA is. It folds into 3D shapes and the shapes determine what it can do. It's like a piece of paper. You fold it into a cup. Your function is now to hold water, fold that same piece of paper into an airplane you were born to fly. Same with RNA. The way it folds determines whether it can do chemistry or just sit there being useless. And early RNA molecules, they cycled through thousands, maybe millions of possible folds, most of them absolutely useless, like a slinky after literally the first time you use it. But every once in a while, purely by chance, RNA would fold into a shape that could actually do something. Those useful shapes. We call them ribozymes. So to be crystal clear, ribozymes is just a rename of RNA after that RNA folded into a specific shape before it folded. It wasn't a rib zyme, it was just RNA after folding into a useful shape, rib zyme. So why does RNA fold, like is it trying to save the world thinking, you know, I gotta get this bubble full of weird RNA strands and amino acids to the kind of complex beings who listen to science podcasts. For fun, my origin story will be known. It says RNA dramatically no. RNA doesn't know these things. It doesn't think it reacts. Remember how I said RNA is like a nerd rope? Well, we're sticking with it. Now instead of the nerd colors being scattered about the gummy rope, try to think of what it might look like if there were clusters of the same colors, the same four colors intermittently positioned on the rope. Now imagine that blue and yellow are somehow magnetized. They were drawn to each other and so was the green and purple. The colors are arbitrary, so that when RNA folds, it snaps these magnetized colors together to form a shape and each color well, they're nucleotides usually just stated with one letter. A pairs with u and g pairs with c and y does it fold to begin with. Water. Water helps RNA fold because the bases prefer pairing with each other over being alone in water. When they pair, they create these water resistant zones like molecular umbrellas, protecting each other from the rain. This pairing plus R a's natural love. And hate of water hydrophilic and hydrophobic respectively causes RNA to fold into specific shapes. Like imagine your A nucleotide and a UG or C, or you know. A nerd and you're out in the rain with only half an umbrella. It's useless. You're getting drenched. Your hair is ruined, morale is low. Then you spot someone else approaching with the other half of the umbrella, and he's, he's carrying a cake with, with no cover. He's getting poured on. He needs a full umbrella too. Why is he carrying an open cake? Well, we don't know. Let's not dig too deep into his life choices. The man only owns half an umbrella for God's sake. But so do you. So we'll continue. So when your two halves meat boom, a full umbrella forms, you're both drier, happier, and because it looks like a, it's gonna rain for well the rest of forever, you decide to stick around. Now imagine tons of these half umbrella people all holding onto the same flexible rope. They're walking around trying to find their matching half while still gripping that rope. Every time two halves connect the rope bends and loops into a new shape. So. Picture this from above, like if alien overlords were watching this ridiculous scene play out. Most of the time they just see meaningless shapes. But every once in a while, purely by chance, the rope would fold into something that looked like it was designed to do something. Maybe signal that they needed cake covers or something. But the important part to know is that this was all by chance. Nobody was trying to form a shape. Nobody was trying to become something that would do chemistry or make a tool. They were just trying not to get soaked. That's RNA. Folding bases don't fold to make a cool structure. They fold because pairing keeps them chemically happier in water and the overall shape is just the rope twisting into whatever formations the pairings force it into. So that's a very long way of saying bases pair up. RNA folds shape happens, and every once in a rare while that shape can actually do something. And if you think about it, a pretzel like structure is way more stable than some floppy, wet noodle. Once RNA folds into those tighter twister shapes, it becomes more resistant to breaking apart. So let's make sure we got this a little checkpoint here. RNA folds into 3D shapes, so it's not just a straight line. Folding happens because of water bases. Pair up A with u, g with C, and hide from the water shape equals function. How it folds determines what it can do. Most folds are useless, but every once in a while you'll get a useful shape. Useful folded. RNA is a rib zyme, and that's just what we call RNA that can do chemistry. RNA was like a transformer, you know, at first it's just a boring truck or car, but once it folded, it could save the world. Well done rib nucleic prime. Okay, so now we understand folding. We got ribozymes are useful folds, but I still haven't explained what it means to do chemistry. So let's fix that. When RNA folds into a useful shape a rib zyme, what it's actually doing is catalyzing reactions. Catalyze simply means to speed up a chemical reaction. It's a verb, not a noun. English people. That one's for you? Language arts. And I never really vibed, so we actually use the word catalyze in everyday life too. For example, the assassination of Archduke, Franz Ferdinand was the catalyst for World War I or the Pandemic was a catalyst for remote work becoming normalized. But in science, it just means to speed up a chemical reaction without catalyst. Some reactions would take literally millions of years with a catalyst seconds. It's like the difference between walking from New York to LA versus taking a plane. I mean, you're gonna get there either way, but one's happening in your lifetime and one's not. And an enzyme. An enzyme is just a molecule that does the catalyzing, it's the plane going to la. In the last analogy, ribosomes are just RNA enzymes. Enzyme is the general term rib zyme is the specific type. When it's made of RNA. So enzymes make reactions happen fast enough to be actually useful for life. Your body has thousands of different enzymes right now, breaking down your food, copying your DNA and making new molecules without enzymes, you'd be dead before your breakfast could even start digesting. This isn't me being dramatic to like make a point. The chemical reactions needed to break down. Your breakfast would literally take years on their own, but enzymes in your stomach catalyze them. So they happen in minutes without catalyst, you'd still be working on yesterday's toast or you know, like last year's toast. So catalysts are enzymes. Enzymes are catalysts. Einhorn is finkle. Finkle is Einhorn, and there's just a small caveat that's only in biology, just FYI, because of the nature of the word catalyst. Not all catalysts are enzymes. Since the word is used in everyday life as. Told previously. So like archduke is not an enzyme. I'm sure you would've figured that out, but I wanted to say the archduke is not an enzyme because I doubt that was ever said before. So here's a super simple scientific example. If you put a tiny bit of yeast or blood. But hey, let's stick with the yeast, shall we into hydrogen peroxide? Now, normally hydrogen peroxide breaks down very slowly into water and oxygen. Hydrogen peroxide, H2O two, it's naturally unstable. It's got an extra oxygen atom compared to regular water, and that oxygen, oxygen bond is weak. So it wants to break apart into water. H2O. And oxygen gas, O2, which are more stable. But normally this takes forever years even. But if you add yeast, which contains an enzyme called cataly, the reaction happens instantly. It foams up like crazy. Nothing new was created, and the enzyme isn't used up. It just made the reaction faster. The enzyme grabs the hydrogen peroxide molecules and just rips'em apart, like Hulk Hogan, ripping his shirt off. Bam, water and oxygen gas done in seconds. Then it grabs the next one and the next one over and over. So when you dump yeast into a bottle of hydrogen peroxide, you are unleashing millions of catalyst enzymes all doing their one job simultaneously breaking apart hydrogen peroxide molecules as fast as they can find them, and all that oxygen gas being released at once. It creates bubbles, tons of them, and that's the foam you see shooting out. It's basically a tiny oxygen gas volcano. If you've ever seen that elephant toothpaste demonstration where colored foam just shoots out of a bottle, all super puffy, like that's this reaction just with some soap and food coloring for added drama. The catalyst enzyme in yeast is breaking down hydrogen peroxide so fast. That the oxygen gas bubbles create a foam volcano. And like I said, the cool part about enzymes is they don't get used up. They're like a slide at a playground. Kids or molecules go down the slide or get transformed, but the slide itself doesn't change. It just helps the kid get from the top to the bottom way faster than climbing down would take. And the slide stays exactly where it is ready for the next kid. I, I always picture these enzymes like the army of the dead from Lord of the Rings, return of the king. You know those Green Ghost warriors, they just swept through taking out all the orcs, never being used up, never tiring, ready to go again at a moment's notice. Of course, until Aragorn said, they fulfilled their oaths and released them, even though they'd be very nice to have in a tight spot. So when I say RNA, ribozymes could catalyze reactions, which means. Folded. RNA made things happen faster. I mean, RNA with their half umbrella nucleotides randomly connected, to make a shape that could specifically speed up chemical reactions. RNA was acting as an enzyme. I know. So crazy. Perhaps you're not as impressed as me, so. Let's, let's pop to the future really quick to around 1980. The music was hopping, the hair was big, and the pants, well, they broke all sorts of wind. Insert inappropriate giggle here. Science at that time had a chicken or egg problem. They knew enzymes were needed to make RNA and d, NA but RNA and DNA were needed to code for enzymes. So RNA and DNA needed enzymes. But enzymes needed RNA and DNA. It's like a circle. So which came first? How did life even start? It's just a dog chasing their own tail for a while there until the answer was finally figured out. With this super cool discovery by Tom Check and Sidney Altman. In their experiment, they found that RNA could act as an enzyme, meaning it could catalyze reactions all by itself. They called these catalytic RNAs. Ribozymes. That's what we just learned. And this was huge because it finally explained how early life could function before anything else existed. It wasn't the chicken, it wasn't the egg. It was a completely different third thing, RNA, acting like enzymes when no one had even thought that was possible. They literally won the Nobel Prize in 1989 for discovering ribozymes and filling in a massive blank in our origin of life history. This was like the top story of the decade, and you just learned it on a. Tuesday. How cool is that? So, so maybe you're like, uh, how cool is that? You tell me. Well, I shall, dear listener, I shall, and I like that you're asking questions. You precocious. Little scam you. So why RNA creating Ribozymes is such a wild discovery is because we know how catalysts work today. And today, specialized protein enzymes do all the heavy lifting. They're efficient, precise, ridiculously fast, and built with 20 different amino acids that give them chemical superpowers. RNA, by comparison, has four letters, almost no chemical variety. It wasn't made to catalyze. It doesn't have the bells and whistles that proteins do yet. Somehow early RNA MacGyver itself into folding into shapes that could catalyze reactions. Anyway, this should not have been possible, and yet it happened. It's like if instead of the army of the dead tearing through the enemy, it was one of the most unlikely creatures of all a hobbit that somehow managed to do the same thing. Or if you're not into Lord of the Rings. It's like if a modern bread maker showed up 10,000 years ago and looked at someone making bread and was like, I'm, I'm sorry. What machinery are you even using? How is this even making bread? That's ribozymes. RNA was doing chemistry with almost no equipment, no diversity, no specialized tools, just folding and hoping for the best, and it wasn't pretty, it wasn't efficient, but it was enough and somehow it worked well enough to jumpstart life. So let's do another checkpoint here. Quick review. Catalyze is to speed up a chemical reaction like using a plane instead of walking to la. Enzyme is a molecule that catalyzes, that's the plane itself or the army of the dead. Rib enzymes is RNA. Molecules that act as enzymes. RNA folded into useful shapes, which is like, you know, using the Hobbit instead of the army of the dead. Tom Check and Sidney Altman won the Nobel Prize in 1989 for discovering ribozymes. This solved the chicken or the egg problem. RNA could do it all before anything else existed. So, I know there's a few new words this episode, but don't stress too much about the vocab. Like you don't need to memorize it, you'll just wanna grasp the core concept. But if you do wanna memorize it, I, I made up this rap for you. I. Get out, get outta here. I'm not going to wrap for you. That's season two stuff, obviously. But honestly, just knowing the core concepts on what these can do will be plenty. We're just building a foundation here, so you, you won't need perfect recall. And maybe if the words rib zyme catalyze enzyme molecule, organic molecule, if they ever come up on a trivia night, you might just pull this from your memory bank. Astounding your friends and onlookers alike. So now we understand. RNA was folding into shapes that could catalyze reactions. It was acting as its own enzyme. But here's the problem. RNA has only four bases to work with. So RNA needed more options, more tools, more chemical diversity, and that's where amino acids come back into the picture. And it's been a second since we talked about them. So, quick recap. Amino acids have a carbon anchor with three things always attached. An amino group and an acid group, and a hydrogen atom. That's the basic Mr. Potatohead body, always the same. And then there's the fourth thing, the side chain. And this is what changes between amino acids. The side chain is like the MR potato head accessories, the bling. Some are tiny, some are bulky, some love water, some hate it, some are charged, some aren't. There are 20 different amino acid, MR potato heads, 20 different personalities, all because of different side chains. So how did amino acids come into the picture? How did they finally get dragged into the workload by the big sibling, RNA? Well, it was by accident or mistake. RNA was doing its thing, copying itself, folding into ribozymes catalyzing reactions, but sometimes. When RNA folded into certain shapes, it would accidentally grab onto an amino acid floating nearby. Not because it was trying to, not because it had a plan, but just because of chemistry. Like remember those half umbrella people pairing up to hide from the water? Well, let's just say each time they paired up the full umbrella, achieved chemical superpower, sometimes it fully repelled water. Sometimes it became charged negatively or positively. And now amino acids are in the picture picture like knee high, Mr. Potatohead people all with different accessories, which gave them superpowers too. And there are just a bunch of'em, and they're walking around in the rain. Then imagine a potato head walked by, a positively charged umbrella group, and he's negatively charged. Well, he'd be compelled to come and join them, and when he settles into that little alcove under their umbrella, everybody's more stable, more comfortable. He helps hold the umbrella with his little plastic white arms, and they all stay like that, stuck together by chemistry. So that's what we mean by just because of chemistry. It wasn't planned. It was chemical attraction charges pulling on each other, shapes fitting together, molecules finding their most stable arrangement. And here's where they get put to work, sometimes that amino acid, that little potato head sitting in the pocket. Would actually help the umbrella people do their job better. Like imagine the umbrella people are trying to stick two molecules together. That's the catalyst, right? But their umbrella poles can only reach so far, or they're struggling to hold both molecules in the right position. Then this little potato head, well, it settles into the pocket with his plastic little arms and his accessories, his side chain bling, and suddenly he can reach things. The umbrella people can't. He can grab a metal ion, he can create a little hydrophobic space where water won't interfere. He can hold one molecule steady while the umbrellas handle the other one. He becomes part of the team. The reaction that was taking forever. Now it happens way faster because you've got RNA structure plus the amino acids, chemical tricks working together. Pretty cool. Well then the next big thing happens in 1999 ing Asray. And Yaris showed that RNA could stick. Amino acids together. RNA was acting like a construction worker, building amino acid chains. Basically the umbrella people or RNA, were now grabbing different potato heads or amino acids and linking them together. This is huge, but why? Why was this such a big deal? Well, because one amino acid by itself, as we talked about, is helpful, but still limited. You get one chemical trick, whatever that amino acid side chain can do, but string together 5, 10, 20 amino acids. Now you've got a chain with multiple tricks, multiple accessories. I mean, dang. You got glasses, earring, mustaches, multiple superpowers, all working together. And those chains could fold up into shapes just like RNA does, creating even more complex tools. And those chains could do chemistry. That individual amino acids or RNA alone just couldn't pull off Now. Here's a cool part. Once you link multiple amino acids together into a chain, that chain is too big to fit into those little RNA pockets, but it doesn't need to fit those chains can wrap around the RNA or they work alongside it like. The potato heads formed a line holding hands, some standing next to the umbrella people, some extending outwards. Those lines. They became structural support, extension, arms helper tools, all working with the RNA as a team. And by structural support, I mean that these early chains. Amino acids would protect RNA because remember, RNA is fragile. It breaks down easily. That hasn't changed, but if you wrap an amino acid chain around it, suddenly that RNA is way more stable. Or if the RNA folded into a useful shape, these amino acids or potato heads would hold it in that shape, making sure it didn't collapse. It's like wrapping an ankle. After you sprained it, you get support and it holds everything where it needs to be so you can do what needs to be done. So now, RNA wasn't just doing chemistry for itself. It was starting to build with amino acids without any help from proteins, which like we stated in the 1989 Nobel Prize, this was a wild discovery. So how did RNA like actually make these chains of potato heads? Well, the umbrella people, certain ribozymes had special pockets positioned near each other. Two potato heads or amino acids would land in each of those pockets held in just the right spot. Then the RNA would help them link their hands together. That's called forming a peptide bond, which is the chemical connection between those amino acids. Once they're holding hands, they're stuck together as a chain. Then another potato head lands nearby. The RNA grabs him. And puts him on the chain and the line gets longer. The umbrella people become assembly line workers, snapping potato heads together one by one. So RNA was the Swiss army knife of early life information storage enzyme and amino acid connector. It was really doing everything. It's like if someone today said, I can build a car engine using only stone tools and no modern technology. And you'd be like, wait, that's, that's impossible. You need precision machinery to build engines. But if they proved they could do it, even crudely, that would be huge because it shows the first step was possible without all the fancy stuff that came later. And that's what Yaris and his team did. They showed RNA could grab and assemble amino acids before all the fancy protein machinery evolved. So let's do another recap, another check-in. Amino acids floating around were chemically drawn to the pockets made by Ribozymes, folded up RNA or potato heads joined the umbrella people. Once the amino acids were there, they started helping the RNA with chemical reactions. Their side chains or their accessories provided chemical tricks. RNA didn't have. Then RNA started linking amino acids together, snapping them into chains. These chains got too long to fit in the pockets, so they wrapped around the RNA or worked alongside it, providing protection and structural support to keep the RNA stable and properly folded, like taping up a sprained ankle. So let's talk a bit more about amino acids. Our potato heads. When you stick two amino acids together, you get a dye peptide, three amino acids, tripeptide, a bunch of them. That's a polypeptide. And when polypeptides get long enough to fold into functional shapes, that's a protein. But we're not at proteins yet. We're at the messy early stage. We're at simple polypeptides, short chains of amino acids. Maybe 5, 10, 20 amino acids long now it is indeed amazing. RNA was linking with amino acids, but they were doing it much like they did everything else just kind of haphazardly because RNA doesn't ever really seem to know what it's doing. It's sort of like, uh, a kid's first go at Tetris. And they're flying shapes together, holding down the down button. Ls are missing squares lines are missing their perfect match. You're sweating in the corner. Just try turning the piece a little Timmy. Oops, missed another. It's no big deal. The shapes are piling up, coming to the top, but then purely by chance, one of the shapes fits perfectly and you see the line blink and disappear. That's what's happening with these lines of amino acids, these polypeptide chains, they're just getting lined up randomly, but every once in a while, the chain can actually do something. And how does this happen through mutation? Now, when I say mistake or mutation, what I mean is a change in the genetic sequence or the directions of what normally happens got changed, usually caused by a copying error or something in the environment, giving that molecule a little shove in a different direction. The same reason X-Men are called mutants, their DNA got tweaked, upgraded, changed, giving them a different biological recipe book than the rest of us. Or, you know, the mutants at table nine. Yes. Adam Sandler is now helping us learn molecular evolution. Is there anything he can't do? So RNA was copying itself, making mistakes, and every once in a while one of those mistakes created an RNA shape that was really good at grabbing amino acids and sticking'em together. That mutant RNA, that made a functional peptide chain. Well, those better peptides helped that RNA survive better, and then natural selection took over. So these peptides changed everything. But, but why? I mean, what could these early crude peptides do that RNA couldn't? And remember, peptides are just a chain of amino acids, linked potato heads. Well, as stated before, they could do chemistry better than RNA. They could protect RNA and they could fold into more complex shapes than RNA could. And how is all of this possible? Well, this is where the 20 different amino acids really shine. RNA can fold into Shape Shore, but it's limited. It's got the four letters to work with. Peptides have 20 different types. They have charged amino acids, polar amino acids, non-polar amino acids, aromatic amino acids, and there's also special cases. With this diversity, you can build catalysts that are so much better at speeding up reactions than ribozymes ever were. So peptides are the specialized workers that RNA so desperately needed. So let's zoom out for a second. Picture early life on earth. Now let's move into warm ponds or near a hydrothermal vent. And let's slide into the protection layer that the fatty acid bubble gave. And you've got inside. RNA, storing information, copying itself, folding into ribozymes, and now simple peptides doing chemistry. Stabilizing. RNA, expanding on what's possible. It's a team now, RNA is still running the show. It's got all the information. It's calling the shots, but tides are doing the heavy lifting like like Vini and Sik from Prince's Bride, the Brains, and the Braun, and out. Here's the key. This wasn't planned. This wasn't designed. This was just chemistry. Finding a better way. Natural selection took over Protocells that happened to have helpful peptides inside them. Well, they survived better. They copied themselves more efficiently. They out competed the proto cells that were still trying to do everything with RNA alone. And over time, and we're talking hundreds of millions of years here, the cells with the best RNA peptide partnership, well, they became dominant. Now, I'm sure there's some people out there thinking, you know, preposterous, ridiculous, outlandish, absurd. How do they keep coming up with these beneficial mutations? It seems a little too convenient, don't you think? And I, I know I'm poking fun, but I honestly can totally understand that train of thought. However, what you have to remember is that for every one beneficial mutation that was selected for, there were millions of deleterious mutations, mistakes that killed the RNA strand then and there, or eventually we only know of the beneficial ones because that's what was selected for. That's what got this far. You know, back when I worked in a genetics lab, we worked with tons of mutant plants, and let me tell you, most mutations are not the superhero origin stories. They were stunted, brittle, missing pieces of their cell walls, or sometimes they just wouldn't grow at all. Evolution makes beneficial mutations sound glamorous, but the truth is, most genetic changes break things. Natural selection just quietly throws those out. No, think about it like baking cookies. Say you're making cookies, and the recipe is two cups of flour, half cup sugar, quarter teaspoon salt, three eggs. Now a mutation comes in and changes one of those things, the Lord basically ruin the recipe. Right? Well, most changes would, but what if by chance it changed half cup of sugar to one cup of sugar? While not good for diabetics or people on diets, I bet those cookies would taste a heck of a lot better when you put your cookies out to eat. More of them would get eaten and you'd make more of those because they won the taste test. You know, suck it berry. But think if that one went to any other place in the recipe. There would not be enough flour if there was only one cup or way too much salt or not enough egg. If you made those cookies and put them out, they would not get eaten and you would not make them again. The only place that one could go and be beneficial would be by the sugar. That's evolution. Millions of bad mutations. Occasionally one good one and that good one gets copied more. Okay, so RNA has helpers now peptides are doing the work. RNA couldn't do well. Everything's better, right? Well, yes, but RNA still had one. Massive glaring weakness. Information storage. See, peptides could help RNA do things. But RNA was still responsible for storing all the instructions, and RNA as we have established, is very fragile. It breaks down in heat. It degrades over time. It's chemically unstable. And as life got more complex, more reactions, more molecules, more peptides being made, the information load, got heavier. RNA, needed to store more information, more instructions for longer periods of time with fewer errors. RNA was drowning. Again, different problem this time, but still drowning. It needed a better filing system. It needed something stable, something that could last, and something that could store vast amounts of information without falling apart, and that's where the next innovation comes in. So let's zoom out and see where we are. Episode one. We had RNA doing everything alone, exhausted, fragile, maxed out. This episode, RNA got help. Amino acids were already floating around from the very beginning. Miller and Yuri made them in a bottle. They were in those proto cells right alongside RNA, but then RNA figured out something revolutionary. It could fold bases paired up to hide from water, creating 3D shapes. Most shapes were useless, but some belzy could catalyze reactions. RNA became its own enzyme. Tom Check and Sidney Altman won the Nobel Prize in 1989 for discovering this. But RNA was limited. Only four bases, only so many possible shapes. Then through mutation some RNA rib Zyme started grabbing amino acids floating nearby, and sticking'em together into peptides. And those peptides, they could do chemistry, RNA couldn't better catalyst, hydrophobic pockets, metal coordination, structural support. It was a partnership rNA had the information, peptide had the skills together. They made early life way more capable. But RNA still had a storage problem. It was fragile. It couldn't reliably hold information long term, and life was getting more complex. More instructions, more reactions, more heat. RNA needed a backup system and through another happy accident, a mutation, a copying error, one missing oxygen That backup system emerged next time on from cells to us. DNA arrives the stable double helix filing cabinet. That would become the foundation of every living thing on earth. RNA finally gets to delegate. The queen arrives and the government learns to read her decrees. Now, one last thing before we go. Everything you heard today represents the best scientific understanding we have right now. We can't rewind the universe and watch life form. So scientists work like detectives. You know, they piece together clues from chemistry, biology, and experiments we can run today. So when I say things that sound definitive, like amino acids were around very early on, you know, that's not scripture. It's a hypothesis supported by evidence, and it's always open to refinement. As new evidence comes in, parts of the story may get refined, adjusted, or even completely rethought, and that's not the flaw of science. That's the whole point. Science doesn't deal in final answers. It deals in better ones. Oh, thanks for joining me on this biological journey. I'm Jackie Mullins, and this has been from Cells to Us. How.