Ep 3 - DNA

RNA was first—but DNA changed everything.

This episode explores why life switched to DNA for long-term storage and how that shift made complexity possible.

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. Last episode was a big one. You did great. We covered a lot. RNA was exhausted doing everything, storing information, catalyzing reactions, copying itself. It's like that Mom of eight kids bags under her eyes desperately needing help. And help arrived and that help was amino acids, simple organic molecules, which were floating around in those proto cells the whole time. We've come to know them as Mr. Potato Heads. Each one with a different side chain accessory that gave them different chemicals, superpowers. And RNA through its folding magic, started grabbing them and sticking them together into peptides, which are just chains of amino acids linked together. Those peptides became workers. They could do chemistry. RNA couldn't handle well, better catalyst, hydrophobic pockets, metal coordination. They could stabilize RNA, protect it, help it function better. So RNA finally had its employees. The cell business is about to launch, but there was still one massive glaring problem. Storage. RNA is fragile. It breaks down in heat, degrades over time, falls apart under stress, and as life got more complex, there was more reactions, more peptides being made, more heat being generated. RNA was trying to store more and more information on what was essentially tissue paper. It couldn't last. RNA needed a filing cabinet, a backup system, something stable that could store information long term without falling apart. So Earth is kind of turning into Bernie Sanders. You know, once again, I'm asking for your changing support. Something's gotta give. That was a horrible Bernie Sanders, And through another happy little accident, that system emerged. Today we're talking about DNA. Now, at first, this might not seem like it takes much of a load off. DNA is just taking the storage job kind of lame. But honestly, can you imagine Tony Iron Man Stark doing what he did without pepper pots? He didn't even know his own social security number. That's what DNA is doing for RNA, taking over the bookkeeping. Why was DNA so much better at this? Well, for starters, DNA has that famous double helix structure, a twisted ladder. That shape gives it built-in backups. Also, DNA is missing one tiny oxygen atom that RNA has. Sounds like a small deal, but that missing oxygen is the difference between stable archive and you know, oops, I dissolved in a puddle. Okay, so we get that we need DNA for stable storage, but how does this happen And when, like it took a lot for the simple, I did air quotes, which is super effective on a podcast simple, RNA to form. How did this more complex double helix, DNA, do it. Well, DNA didn't show up fully formed. Like, surprise. I'm here to save the day. It happened over a lot of time, but you know, don't worry if you got sentimental about RNA because you learned its whole origin story, fear, not RNA will be sticking around. So remember from last episode how mutations work when RNA copies itself, sometimes it makes mistakes, most mistakes. Deadly, not superhero origin story. The RNA falls apart or stops working, but every once in a while, a mistake turns out to be genius. This was one of those times rNA was copying itself as usual, and somewhere somehow a copying error happened that removed one tiny oxygen atom, just one. From the ribose sugar in the RNA backbone or in the gummy rope of the nerd rope. That's it. One oxygen atom goes missing. Doesn't sound like much, right? But that one missing oxygen atom made the molecule way more stable, way more resistant to breaking down way better at long-term Storage. That molecule was DNA. Deoxyribonucleic acid diox literally means without an oxygen And just like evolution's greatest hits, DNA was just a mistake that turned out to be genius. Bob Ross would be proud. A happy little accident that became the foundation of all complex life. So why does losing one oxygen atom make such a huge difference? That extra oxygen atom and RNA makes it chemically reactive. It's like having a loose thread on your sweater, one little tug and things start unraveling RNAs extra oxygen. Makes it vulnerable to breaking apart, especially in the presence of a bases, alkaline additions or, you know, certain enzymes, a DNA without that oxygen, well, it's way more stable. You now have put on a perfectly knit sweater, no loose threads happening. It holds better together under stress. So that mistake or mutation of one less oxygen gets repeated more and more frequently because DNA isn't breaking apart like RNA would. It's lasting longer and creating more stable copies. And before you know it. Bam. You know, around 300 million years fly by, and now most successful protocells have all four components, R-N-A-D-N-A, peptides and a protective membrane working together. But that wasn't DNA's only advantage. Here's where DNA really snagged the information storing job from RNA. Remember how I said RNA is single stranded? It's one long nerd rope folding up on itself. Well, DNA didn't stay single stranded as we touched on, but what, like, just because it got stable, two strands appeared. Well, no. What scientists believe happened is this single stranded, RNA mutated into single stranded DNA. And then when that single stranded, DNA locked eyes across the proto cell room with another single stranded, DNA. Well, they knew they had chemistry, so they came near to each other and found out that they were indeed compatible. And not only that, it's actually lower energy for those two strands to bond together than to stay separate, much like RNA folding. So you didn't need some special evolutionary innovation for the double helix to form. It was just chemistry doing its thing. So chemistry says to these single DNA strands, listen, rent is getting expensive. Earth is kind of the place to be right now. Real estate is hot. Location, location, location. Everything would be better if y'all just paired up. And they did. And there was no turning back. The double helix was born. And if you need a visual, there was this amazing meme during Peak Game of Thrones, you know, when it was like not in the last season, and it was Denarius mother of dragons with her two curls in front of her face. One curl was labeled RNA single stranded, and the intertwined curls were labeled DNA double stranded, accurate and hilarious. So, DNA has that famous double helix structure, the twisted ladder, but why does that matter? Well, picture a ladder. The sides of the ladder, the parts where you never actually grab because who grabs the sides of the ladder except Tom and Tom and Jerry cartoons when he has to go down really fast. Anyway, those are made of sugar and phosphate boring backbone stuff. They're important structurally, but they don't carry any information. Exactly like the gummy string of our RNA nerd rope. I know I keep banging away at that comparison, but it's just so dang good. So the rungs of the ladder, the place where you'd actually climb up, that's where all the important stuff is. Each rung is made of two bases, nucleotide letters, and they reach across and hold hands in the middle, making a full rung. And here's the key. A always pairs with t. G. Always pairs with C. Always, no exceptions. A and t. G and C till death. Do them part. Just remember at and g, just like the fleet Topher, from cloudy with a chance of meatballs at and G. Now here's what makes this brilliant. The sequence or the order of those rungs. The order of the letters along one side of the ladder. That's the information. That's it. That's the whole secret. It's like Morris code dots and dashes mean nothing on their own, but string them together in the right order. And you've got a message. DNA is the same exact thing. A TGC. They mean nothing individually, but the order that they're in, that's the instruction manual. It's like every sentence you've ever written is just a remix of the alphabet. The alphabet means nothing by itself, but in certain orders you can basically do anything The. So if the side of your DNA ladder reads a TGC, CAT, something like that, the sequence is the information. It's not pointing to information stored somewhere else. It's not a map to buried treasure. The treasure is the sequence. And because A always pairs with t and g, always pairs with C. If you know one side of the ladder, you automatically know the other side. It's like having a backup. So if something happens to one strand, you can rebuild it from the other one. It's a built-in redundancy. This is why DNA is so much more stable than RNA for long-term storage. It's got a buddy system, much like camp counselor, Lars and heavyweights. Don't worry, nurse Julia. I have them on the body system. I'm Just awful at accents. I should stop, but I might not. So compare this with RNAs, one strand, those half umbrella nucleotides freaking out in water and just attaching to, you know, anyone that'll make them dry. Nucleotide hussies if you ask me. But no judgment. Chemistry is chemistry, but that panicked attachment, there's no rhyme or rhythm. And RNA is single stranded, so there's no buddy system. If it breaks, there's no mirror copy to rebuild from. It's just gone forever. But in DNA, if a part of a strand gets ruined, you just look on the other side of the ladder and you can build it back how it was, and your day will continue. Now, I'm sure most of you have seen spy movies and the backup plan never works, and you go into a montage where they knew that all along and here's the real plan, and I get it. Yes, you're right. Sometimes the backup strand doesn't work. Sometimes the whole rung does get damaged. It's not unheard of. It's just a lot more rare. Also, just to clear this up, like what information was RNA and DNA even holding at this point? I mean, right, they're not making bodies or plants or whatever, they're just holding down a leaky membrane full of rogue potato heads, amino acids, freaking out half umbrella people scared of the rain, RNA and new single stranded, DNA. Pairing up with others like it's the love connection. Maybe you're like, yeah, this all looks like pandemonium to me. What instructions are so vital to keep safe? And that is a fair question. The information at this point, well, it wasn't complex. It wasn't blueprints for eyes or leaves or anything fancy. It was survival instructions. It was the bare minimum. Here's how to copy yourself. Here's how to fold into a shape that works. Here's how to grab amino acids and stick them together. Here's how to make peptides that will help you with your chemistry. That's it. That was the instruction manual. So yeah, it looked like chaos, but buried in the chaos were instructions for how not to fall apart and in early life, that was everything. The complex instructions, the ones that built bodies and brains and butterflies. Well, those come way later. But they all started here with those simple survival recipes being copied, tested, and refined over hundreds of millions of years. You know, think of it like baking early proto cells had recipes that said, Hmm, you know, add some flour, you know, some sugar. And some eggs, whatever. Whatever you can find, add those eggs. Then you get some like redish stuff, but it's different every time. The recipe is more about the process than the actual product. In the future, after the genetic code evolves, recipes will be like, you add exactly two cups of flour. Exactly. Three eggs, exactly. One teaspoon of salt, and you'll get the same bread every time because the recipe specifies exactly what it needs. But we are not there yet. We're in the messy, nitty gritty trenches of Protocells. So let's pause and make sure we got this a little checkpoint. DNA is missing one oxygen atom compared to RNA. That makes it way more stable. DNA forms a double helix. Two strands paired together, twisted like a ladder. A, always pairs with t. G. Always pairs with C. No exception. Always at and yuk. The sequence of bases is the information. It's like the Morse code or, the alphabet. Two strands is a built-in backup. If one breaks, you can rebuild it from the other. RNA is single stranded. It has no backups, and it's way more fragile. So DNA is basically a really, really good filing system, but files don't do anything on their own. You need someone to read them, you need someone to do what the files say, and that is R a's new job. Okay, so through mutation, DNA emerged stable double helix, perfect for storage, but here's the plot, twist, RNA, mutated to form DNA. And I'm sure a lot of you have heard of DNA in your science classes on the TV on Jurassic Park. You were like, yeah, that's what's in us now. So it must be awesome. Perfect. The deity scent molecule, us, us, us. However, this new DNA molecule well couldn't actually do anything by itself. And like I said earlier, DNA is a filing cabinet, but a filing cabinet just sits there. You need someone to open the drawers, read the files, and actually do something with the information. That's RNA. DNA was completely dependent on RNA to read it, copy it, and turn its instructions into action. And that's still true today. Our modern biochemistry still reflects this ancestral hierarchy, which is why I think it's worth knowing. So, RNA was basically not off the hook at all. It created accidentally something that could only work with R a's help. I mean, that's job security at its finest though, right? I told you RNA would stick around. So like I know I said Tony Stark couldn't do anything without pepper pots, but the actual analogy here would be like Tony would then have to read the book. She kept. Copy it into his own book while translating it into his native language. DNA didn't make it easy on RNA or if you're not a Marvel fan, DNA is like the queen of England. She's an important figurehead, holds all the hereditary information, but doesn't actually do anything day to day. RNA is the entire British government. Prime Minister, parliament, civil service, everything RNA, reads what powers the queen, technically has interprets them, then actually runs the country. The queen DNA is stable and unchanging. The government, RNA, does all the work. So how did this transition happen? When did DNA take over? Well, imagine a bunch of protocells with RNA strands and peptides inside. Then one mutation and this more stable DNA strand starts appearing alongside those RNA strands. At first, you mostly had RNA. And then a little bit of DNA. The DNA was more stable, so it lasted longer. It made more copies of itself without breaking down. The ratio started to shift more DNA, still plenty of RNA, but now DNA was handling more and more of the storage while RNA was focused on the work, it's kind of like if you've ever had a job and your manager asks you to help out, and all of a sudden you're just doing someone else's entire job. It happens slowly at first, but the takeover is real. Your penalty for being good at work, more work. So after this natural selection took over. Protocells with DNA inside survived Better. They could store information reliably and they made fewer copying errors. They out competed the protocells, still trying to do everything with RNA alone, and now this didn't happen overnight. We're talking hundreds of millions of years somewhere in the ballpark of like 300 million years. That's the gap we're covering right now in this one episode. You're listening to 30 to 40 minutes of me explaining 300 to 500 million years of slow, clumsy, messy transitions. Think about how many rounds of trial and error, mostly error. There must have been for me to only need one episode to tell you about the final result, but eventually. Bam. Most successful Protocells had all four components working together. R-N-A-D-N-A, peptides and a protective membrane. Just for a frame of reference, we're now out of the Hadian eon and in to the Archon eon about 3.8 to 2.5 billion years ago. Remember the Hadian Eon was the molten nightmare. Well, the Archon Eon still pretty hostile, but now life is actually happening, so. Let's do another checkpoint. Let's do a recap of where we are. RNA was doing chemistry reading, DNA, coordinating everything like the British government. DNA was storing information stably, it was the Queen of England. Peptides. Were helping with reactions and protecting RNA, the workers fatty acid membrane. Was keeping it all contained. The information being stored is basic, but so necessary. So now we have a team, DNA storing information, RNA, reading it and doing chemistry and peptides, helping with all the, he helping with all the heavy lifting. But here's the thing, the system is still pretty crude. It worked, but it was messy, inefficient, and random. Before we get to how the system got organized, we need to talk about how this DNA storage thing actually got discovered because humans didn't always know about DNA, and when we finally figured it out, it was a really big deal. So how long have humans, known about DNA? We've actually known DNA existed for a while. Scientists figured it out back in the 1860s. For reference, Abraham Lincoln is president and child labor laws are considered silly and outdated. That's a long time ago. People were not using toilet paper regularly at this point, but we knew DNA was in a cell. Wild times, but for almost a hundred years, nobody knew what it actually looked like. Nobody knew the structure, and without the structure, you can't really understand how it works. Then in 1953, everything changed. James Watson and Francis Crick. Two scientists at Cambridge published a paper that was barely a page long, and in that one page. They described the double helix, the twisted ladder, A pairs with t, g pairs with C, the whole thing. It was revolutionary. That paper might have been the most important scientific publication in the 20th century, but here's the part that often gets left out. They didn't figure it out all alone. Rosalyn Franklin was a chemist working at King's College London, and she was using X-Ray Crystalography basically shooting x-rays at DNA and capturing the patterns that they made to figure out its structure. And she got so close. She had the data. She had an image, photo 51 that clearly showed the helical structure, and then her colleague, maurice Wilkins showed that image to Watson and Crick without her permission. They saw it and immediately knew that's a helix. That's the shape. And they used her data to build their model. Watson and Crick published became famous and eventually won the Nobel Prize in 1962. Rosalyn Franklin. Well, she died of ovarian cancer in 1958, likely caused by all that x-ray exposure. She was only 37 years old. She never got the Nobel Prize, but they don't give them posthumously. Would things have been different if she were like a man? Uh, who knows? Maybe. But in 1950, science, being a woman certainly didn't help. So the very least I can do is mention her on my podcast. Add away a Dr. Franklin. So understanding DN a's structure unlocked everything before 1953, we knew DNA existed, but we didn't know how it worked. After 1953, we understood how information is stored, how it's copied, and how it's passed down. This discovery led to modern genetics, molecular biology, the human genome project, CRISPR gene editing, basically all the modern medicine and biotech. That one page paper, changed the world. All right, so let's do our, our quick recap. DNA structure was discovered in 1953 by Watson and Crick using Rosalyn Franklin's data. Photo 51 showed the helical structure, which is the twisted ladder. Franklin died in 1958. At age 37, never receiving any credit. This discovery unlocked modern genetics and everything that came after. Alright, well history lesson over. Let's go back to early life. So we've talked about DNA being stable storage with a built-in backup, but here's what makes it truly brilliant, and I mean that like how British people say it, which I think is more meaningful. So how DNA copies itself, remember how the double helix has two strands paired together like the rungs of a ladder with either an A with a T or a G with a C? Well then it's time to divide. And here's what happens. The two strands unzip, they separate down the middle, like opening a zipper and splitting the ladder. But both sides get a rung. Now you've got two single strands each with its sequence exposed. And this is what makes DNA so special because each strand Becomes a template. If one strand reads A TGC, the new strand building off of it has to be TAG. The bases pair automatically A grabs, TG grabs C. So maybe you're asking questions here in your mind like, oh, DNA on zips now. That's cool, I guess. And where are these bases coming from? Totally legitimate questions. So unlike today. Like where DNA has a whole molecular pit crew to unzip it carefully. In the proto world, it was physics that unzipped, DNA, not biology we're out of the Haiti onion, but the archon eon is no day at the beach. DNA isn't sipping a frozen cocktail with a little umbrella. It's fighting for its life. Earth was hot, hot, hot. The pH was changing constantly. There's plenty of other chaos going on. DNA was held together by its nucleotides, right by the A and t, and G and C paired up in the middle of those ladder rungs. But what held those letters together? What actually held the rungs together? And that's hydrogen bonds. A and t has two hydrogen bonds. G and C has three hydrogen bonds. Now, hydrogen bonds are very sensitive to heat and fluctuating chemistry. So say the heat got turned up, there was a change in salt concentration, or the puddle that you were in started drying out. DNA would then peel apart naturally as those hydrogen bonds broke. So if you were announcing what was taking place to onlookers or something, you wouldn't be like, oh, and see how the DNA unzips to have itself copied. How wondrous. Like you were in National Geographic describing a blooming flower. No, you'd be like an announcer after someone just took a big hit. It's more like the environment shook the ladder until the rungs popped loose. That DNA has been split right apart. That'll be felt tomorrow morning. Folks, the strands didn't unzip on purpose. They drifted apart because the conditions forced it to happen. And now we have unzipped, DNA, just chilling. That's when the copies can be made. But where are these nucleotides coming from? Well, just like amino acids, they were already there floating inside and around the protocells. And remember the fatty acid membrane? Well, it's like that bouncer who let you back into the same bar you got kicked out of the night before for jumping on a table, speaking about a friend, obviously. Point is the membrane wasn't great at its job. Lots of things got through. And because of this. Free nucleotides. A TGC could drift into the proto cell, even if they weren't already in there. The proto cell interior was basically a molecular junk drawer. Now chemistry kicks in because A with T and g with C are attracted to each other. So each unzipped strand of DNA is laid out like a strip of magnets. And as soon as any a passes a t it gets pulled in or a C passes a G, and so on, until you get a full copy of the unzipped DNA strand. Again, not because it's smart, not because it's alive, but because it fits. So from one double helix you get two perfect copies. Or you know, as perfect as early proto cell life could manage. Mostly accurate would probably be the better description, I suppose. Each has one old strand, the template and one new strand, the copy, and usually identical to the original. This is why the Double Helix was such a game changer, not just stable storage, self-replicating storage, DNA could make near perfect copies of itself over and over, and with way fewer errors than RNA ever could. And when that proto cell divided. Meaning when the fatty acid spherical Oreo decided it was too big and started pinching into two cells instead of one? Well, each daughter cell got one complete copy of the DNA. Same instructions passed down Any dividing cell that left with a copied strand of DNA usually got what was meant to be passed on. That's inheritance right there. So instead of messy RNA, making clumsy copies of itself and the cell splitting and taking that error prone, copied, RNA, just drifting away like, bye buddy. Hope you find your dad. Well, that replicated RNA probably won't find its dad because it's likely a mutated strand that won't stay stable for long. Just a morbid. Little RNA joke for you. DNA was much better than RNA at this process. Sure. DNA made copying errors occasionally. A wrong base here, a skipped letter there. But here's the thing. Those errors became mutations. Variations and variations are the raw material for evolution. Without copying errors, every cell would be identical forever. No change, no adaptation, no us. DNA struck the perfect balance, accurate enough to pass down working instructions messy enough to create variation. DNA was much better than RNA at this process. This is the mechanism that would eventually allow life to go from single cells to well, everything. Okay. Okay, so now we've got the team assembled. DNA is storing information, RNA is reading it and doing chemistry peptides, helping with the reactions, membranes, keeping it all together. Life is working. Proto cells are dividing, evolving, competing. But of course, here's the thing, this whole operation was still pretty chaotic. Think about it. RNA would read DNA, then fold into shapes, sometimes grab an amino acid, sometimes stick them together with other peptides. But there was no system, no organization, no standardized process. It's like if you had a factory where the workers just kind of showed up and built whatever they felt like that day. Sometimes you get a useful product, sometimes you'd get junk. No quality control. What life needed was organization. A systematic way to translate the information of DNA into specific, precise instructions for making specific, precise peptides. Life needed a code, a language, a way to reliably go from this is DNA sequence to this exact peptide. And that's where things get wild because RNA, that overworked British government was about to invent something extraordinary, a code so perfect, so universal that 3.5 billion years later, every living thing on earth still uses it. Bacteria a redwood tree. You all speaking the same molecular language. So let's zoom out and see what we've covered today. Yeah. RNA had helpers now peptides doing chemistry, making life more capable. But RNA still had a huge storage problem. It was fragile, breaking down, losing information through mutation, losing one oxygen atom, RNA, created DNA. More stable, more reliable, perfect for long-term storage. Then DNA got even better. Two single strands paired up to form the double helix. A twisted ladder with a built-in redundancy, A pairs with TG pairs with C at. And if one strand breaks, you've got a backup. But DNA couldn't do anything alone. It needed RNA to read it. Interpret it and turn those instructions into action. DNA became the queen of England. Important, but not running the day to day RNA remained the British government doing all the real work. Watson Crick, Rosalyn Franklin discovered DNA structure in 1953. Photo 51 showed the helix that discovery unlocked modern genetics and everything that came after. So now in our proto cells, we have DNA, our stable information storage, RNA, reading, DNA, doing chemistry, coordinating everything, peptides, specialized workers, helping with reactions, membranes, keeping it all contained. The team is assembled, but the system is messy, disorganized, and efficient. What comes next? Organization systemization a code next time on from cells to us. The genetic code is born life. Invents a language that translates DNA sequences into precise peptide instructions, three letter words that specify which amino acids go where. The code that every living thing on earth still speaks today. I can't wait. And two quick notes for you, wonderful listeners. First off, I'm aware the episode was accent heavy, and for that I apologize. However, this is in no way my resignation of using them, just my acknowledgement that I'm not very good at them. I hope you were able to get through it. I took so many takes of that Mrs. Doubtfire part, but kept laughing afterwards. So what was recorded was. The best I could do. I hope you are still able to enjoy it. Second, I wanna congratulate you on making it three episodes into your origin story. We've gone from Molten Earth to DNA in three episodes. That's 4 billion years of history. Pat yourself on the back, you deserve it, and. Thanks for joining me on this biological journey. I'm Jackie Mullins, and this has been from cells to us. How.