Mutations Explained: The Tiny DNA Changes That Can Change Everything

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Welcome back, guys.
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What is uh uh what is this?
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Like the how many episodes is this now in?
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Three, three uh we're on the second one.
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Well, third if you count the many.
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Three.
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Yeah, yeah, yeah.
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Okay.
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Well, we're somewhere in the 14th season.
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Yeah.
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Somewhere.
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And today we're gonna talk about mutations and genetics.
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So it's not gonna be super, super heavy, but before that, we want to get into some nature news.
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And really the b the big announcement.
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One, I still don't know if I've won the birding competition.
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Or when I say I, I mean we, a team, because it was a team effort.
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The Cheeky Warblers.
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Yeah, the Cheeky Warblers, which is an amazing name.
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I think last time we recorded it was before that, right?
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Yes.
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It was before the competition.
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Yeah, yeah.
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Yes, just before.
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Okay, so very quick re-recap.
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Super, super fun.
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My son and I, we saw 96 species that day, which is so close to 100, like painful.
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But we just we tried to squeeze, you know, find some last-minute ones there at the end, and it just wasn't wasn't working out for us.
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But 96 is 96 is still crazy, yeah.
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Yeah, and so I'm not gonna give away our total, but we did really, really good.
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And we are on unless the other group that won last year saw a ton, we should be pretty darn close because we were right around where they normally so yeah, so we'll we'll see here probably within the next week or so, and or a couple weeks, yeah, probably within the next couple weeks, so we'll we'll know.
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But but we had fun.
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I mean, Luke and I had fun, man.
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I've never I've never birded that hard.
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Like obviously, you guys know if you don't follow me yet on Instagram, Wildly Katie.
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Uh, we did the booby trip, and while that was really fun, and that was like multiple days in a row birding, it wasn't like all day.
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Yeah, and like a 24-hour marathon.
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Yeah, yeah, because we were we got up at 2 30, my alarm went off.
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2 2 30, my alarm went off.
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We went looking for owls, which we heard two screech little screech owl bard owls were like perfect, and then we went to our favorite spot for morning course, which totally paid off.
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We were gonna stay at our first location.
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Then I was like called an audible last second.
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I was like, you know what?
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We could either trespass and win or go back to the spot where I know like is our favorite spot locally.
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So we turn around and hurry up and rush back to our favorite spot, which was totally worth it because that place alone was like 50-something species.
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That's nuts.
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Um, yeah, and so that was so, so worth it.
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So that was definitely the right call.
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And then the rest of the day, like we hit like a lull around like 11.
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We came home because that went out, we gotta let the dog out, auto out.
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Yeah, let the dog out, grab some lunch, and because it's the heat of the day, we took like a 30-minute, well, I took a 30-minute power nap because Luke had been sleeping in the car on and off.
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And then we went back out in the afternoon, and then we got done around like 9:30 or so.
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Because by that point, we're like, all right, we already got some owls.
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Like we went and found a great horn dial.
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Yeah, we went and got found a great horned owl because where we knew it was gonna be, got that one, and then we were just like, all right, cool, man.
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And he slept the whole way home, which I mean the last place because I did one big loop kind of thing.
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But yeah, so we were right down the road for the last one and came home, and he was that kid was passed out.
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But and then of course, the next week was the biggest, like the big day, and Luke already was with me again that weekend, and he was like, Mom, I'm like, no man, I'm still tired from last week.
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It's okay, we're not gonna do it.
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But but it was a lot of we had a lot of fun, and I have a fantastic team.
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It was like maybe like 8 30, 9 o'clock in the morning, and the two other ladies sent me a link and it was a a spreadsheet of like all of our stuff.
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So they're like just as nerdy as insane as I am, being super organized, and like so it was it was great.
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They made it so much easier.
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They saw a lot too.
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So we have we have a really good chance to win, and if we don't, we're gonna be uh neck and neck with with the other group.
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So so we'll see.
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But that was it was a lot of fun.
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We keep having weird birds come up here.
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I don't know if they're being blown up from like a southerly wind, but like in the last like two or three weeks, in here in Maryland, we've had 15 Scarlet Ibis.
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Oh, nice, yeah, yeah.
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Um, a dozen uh like 10 Cuban whistling ducks, I just gotta call them out.
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And an Avenga.
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So like four is here in Maryland.
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Yeah, I've seen them before, but like not in Maryland.
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Yeah, right.
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Dang, that's some good ones.
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That's some good ones.
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I mean, Texas is just odd anyway.
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Again, 634 plus recognized species is is is crazy.
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Bananas.
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Yeah, and so whenever we do get those random ones that blow into, it's a huge deal because then people are like, let's get more.
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But yeah, but yeah.
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Let's see here.
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Other nature news, David Attenborough is like a bajillion years old.
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Happy birthday! 100th birthday, man.
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And he's looks amazing.
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Yeah, like for a hundred way, you'd guess that guy was a hundred.
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I'd be like 80s for sure 80s, yeah.
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But like a hundred truly not a hundred.
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Yeah, nope.
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And he's still still doing stuff, still recording, still narrating.
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He's not nature.
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Right?
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He's just got the voice, right?
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Alrighty, hang on one second, Laura.
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Let me yell at this kid again.
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He's turning up the TV, I can hear him.
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He opened up the door.
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I'm just like, kid.
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That's why I could all of a sudden hear it.
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Okay.
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Alright, into it.
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Alright, so we are like we said earlier, we're gonna be talking about mutations and the tiny changes in DNA that can and how they can create all sorts of just crazy, crazy outcomes from just the tiniest little like the literally the tiniest, like so tiny.
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One might say microscopic.
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Yeah.
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So yeah, just a itty bitty shift.
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All right, Laura, do you want to give like an overview?
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So again, whenever we do these deep dive episodes, guys, it's not like okay, one disclaimer.
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You guys gotta remember one, Laura and I aren't geneticists.
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All right, we are scientists, we are, yeah, like our whole background is in science communication things.
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We took genetics, but only one.
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Like one God.
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Thank God never.
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But it's complicated.
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It is very complicated.
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Again, genetics is the one that I'm I'm fascinated with, but as long as I'm not graded on it, because it is just like so crazy.
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Especially with this stuff where like I can literally imagine like the transcription process and having to like draw the transcription process.
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Right.
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Just that's where it gets into the nitty-gritty.
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Yeah.
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Yeah.
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Yeah.
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So so yeah, but but we keep it at a very high general level because again, our most of our audience is nature novices.
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And so we're breaking down really complex sciences so that's easy to understand.
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So if we do have somebody out there listening that does know about this stuff way more, cut us a break.
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Yeah, chime in, let us know.
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But also cut us a break that it's not gonna be deep, deep dive into this stuff because it is gonna be just high, high, high level.
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Yeah.
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And some of it's hard.
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Well, and if you we did a previous genetics episode, if you want even more base level, like we just did genetics 101.
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You should go back to that one, listen to that one first.
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This is a little more deep.
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And like some of this genetics stuff, especially with this, what we're covering today with mutations, I feel like a lot of it is visual.
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Yeah.
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Um so if you're confused and you're able and not driving, pull up a picture because it will help you.
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Yeah.
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Yeah.
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Alrighty.
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Well, Laura, then do you want to give like just a very high-level quick overview of DNA?
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Like what are mutations?
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Mutations.
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Yeah.
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Yeah.
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So mutations are just changes in your DNA sequence or RNA sequence.
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So mutation, a change.
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So remember that DNA and RNA, which both are inside of you, is made up of different nucleotides joined together with what we call bases.
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Those bases are A, G, C, and T.
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Except if it's an RNA, it's a U instead of a T.
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So we're gonna be throwing some letters around, but those are just base pairs.
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Those are the things, for those of you that are watching this on YouTube, that are linking your strands of DNA together.
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So there's two sides and links them up.
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They're the r the rungs of the ladder.
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Exactly.
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And they always form base pairs of A and T and G and C, except for mutations.
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But normal, or normal, I feel like maybe not normal, but generally they that's what they do.
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So if these nucleotides get jumbled up, or the proteins that make them do, mutations happen.
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And since DNA and RNA are the blueprints for making proteins that do literally everything in your body, stuff can go wonky.
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And these mutations can be caused by different circumstances.
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Could just be a blip in your own code, like all of a sudden your body went rogue for a second.
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Could be UV radiation, could be chemicals, could be like there's so many things that can cause mutations.
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And some of the mutations are beneficial while others are deadly.
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Um, so we are gonna be talking about there are different types of mutations and different problems that those things can cause.
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That's that.
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Um That's that.
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All right.
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Do you want me to go out?
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I can start.
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So we there are different types of mutations, and so Laura and I split them up.
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Um I I I don't know what to call like the groups, though.
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Like there's different names, they're just similar.
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Yeah, they're types of mutations, but the ones that Laura has versus the ones that I have, they are kind of similar.
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And I but I don't know what to do.
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They call similarities.
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Yeah, I don't know what to call that that bigger group.
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So you'll you'll figure it out as we go along.
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So my my first one I want to talk about is one of the mutations that basically turns your DNA kind of like into an autocorrect on the fritz, kind of, but it's frame shift mutations.
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Okay.
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So normally your DNA is read in groups of three.
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So those letters that Laura was saying, it's like comes in groups of three.
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Those little three-letter chunks are called codons.
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And each codon tells the cell which amino acid to add next when building a protein.
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Like some of my stuff happens with frame shift happens within some of mine too.
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Okay, okay, cool.
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Like frame shift if it's like a result of certain problems.
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Yes.
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Yeah.
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So imagine a sense.
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Now Laura said, you know, the letters, but just for simplicity's sake of thinking about it, I'm just gonna use all the letters of the alphabet just to make it easier, all right?
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So think of it if you have a sentence, the cat ate the rat, right?
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Oh, I saw this example.
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Yeah, everything works, everyone understands the assignment of hey, this is a sentence.
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But if I remove just one letter, so it's like instead of the, it's T H C A T A T-E-T, H E R A T, like it's all of a sudden you're in danger.
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And that's an extreme example because sometimes these will just be like one little shift, like doesn't really take much.
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But that jumbling of that shifting just a little bit is basically what a frame shift mutation does.
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It's caused by my problems because I have insertion and deletion.
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You do, yep.
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So a frame shift happens when DNA either gains or loses letters in amounts that are not divisible by three.
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Can you hear that thunder?
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Geez.
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So instead of just changing one word in the genetic instructions, it shifts the entire reading frame downstream essentially.
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Every codon after that point gets read differently because of the the shift a little bit.
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And this is important because proteins are extremely specific.
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If you mess up the instructions, the cells can end up building a protein completely wrong, or sometimes it hits a stop signal way too early, and that protein ends up like weirdly short and unstable.
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Story of my life.
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Um, so so what's wild is that these mutations can range from basically harmless to causing major genetic disorders depending on where they happen in that DNA.
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So a mild example, now mine, each of the ones I'm gonna talk about three different types of mutations.
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I'm gonna do a basic overview, like I just did.
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I'm gonna give you a mild example, an extreme example, and then some of like the research and importance, just so you guys kind of know where we're going with this.
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We'll see, let's see, keep going, keep going.
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We'll see.
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Yeah.
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All right, so mild example isn't catastrophic whatsoever, which I'm sure we learned about this in genetics, but I totally forgot about it.
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Is blood type.
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Do you talk about blood type at all?
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No, I do have substitution, one that deals with blood, but it's not.
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Okay, perfect.
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All right, so your blood type can come down to tiny mutations in the ABO gene, and one of the mutations associated with type O blood involves a small deletion that shifts the reading of the frame protein, which I again I am sure we learned about that in genetics.
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Totally forgot.
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So basically, the protein gets cut short and can't finish the job modifying the surface of a red blood cell the way that type A or B blood does, and the result of that is that's type O.
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Like that's just what it is.
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That's just like a normal, a normal thing.
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So not a big deal.
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While common blood types like A and B are distinguished by simple point mutations, which are single nucleotide substitutions, the creation of the O allele is characterized by deletion that, like I said, shifts that genetic reading frame, rendering the resulting protein basically non-functional.
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And that's it.
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Like nothing too crazy, just you just have a different blood type.
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Actually, arguably more beneficial.
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Yeah, it is the universal donor.
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I'm a negative, and I remember that because I had to get that shot in my butt whenever I was pregnant with Luke because I'm negative.
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Negative being negative sucks.
00:15:32.939 --> 00:15:33.259
Yep.
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One of the what they say is the alien life, the alien one, the negative.
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So that's a very so blood type is a very mild example of a genetic mutation.
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Now, if you swing it completely the other way, frame shift is Tay Sac's uh disease.
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I was about to, so I almost did that one, and I was two, so because I have an insertion and deletion, which I just lumped together because I'm literally was going to talk about the exact same thing with a frame shift.
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I'll just do mine, like I'll just mention mine in passing, but I didn't do Tay Sachs because I was too scared to do Tay SACs because I didn't want to know too much about it.
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I was like, it's too scary.
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It is, it can be very scary.
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I do a very, again, very high overview.
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So in some cases of TASACs, a frame shift mutation affects a hexagene, H E X A, which contains instructions for building an enzyme called the hexosalmodase A.
00:16:27.659 --> 00:16:33.500
And that enzyme is basically part of the cell's cleanup crew, for lack of better terms.
00:16:33.659 --> 00:16:44.220
Its job is to break down certain fatty substances, specifically molecules called GM2 gangliocides, which are inside nerve cells.
00:16:44.459 --> 00:16:58.620
Normally your cells are constantly building up things, breaking things down, recycling materials, and there's a non-stop microscopic maintenance operation happening inside your body every single second of every single day.
00:16:58.939 --> 00:17:09.500
But in TASACs, the instructions for making that enzyme get scrambled badly enough that the enzyme either doesn't work properly or sometimes barely works at all.
00:17:09.740 --> 00:17:17.740
So then that causes the fatty substances that are supposed to be cleaned up just start piling up, basically in neurons.
00:17:18.140 --> 00:17:33.019
And neurons are not exactly cells you want cluttered, like a garage, like stuffed full of stuff, because it needs that clean pathway and those clean well pathways so that you can run literally the instructions through everything.
00:17:33.259 --> 00:17:40.220
And over time, those fatty substances, as they build up in the brain and spinal cord and progressively damage the nervous system.
00:17:40.460 --> 00:17:54.059
Well, most while most severe and well-known form is infantile tasks, what makes it especially heartbreaking is that babies with Tay sacs often appear completely normal at birth and can seem completely fine.
00:17:54.220 --> 00:18:05.180
But then symptoms start appearing within the first couple months, and parents may notice like, hey, they've hit some developmental milestones, but then they start drastically regressing.
00:18:05.420 --> 00:18:10.460
So skills the baby had started to learn just absolutely begin disappearing.
00:18:10.539 --> 00:18:19.980
So it's not like a, oh hey, they regress a little bit because they're, you know, newly acquiring a skill, and your brain is forming all these synapses to be able to do something.
00:18:20.139 --> 00:18:23.420
No, it's like drastically starts disappearing.
00:18:23.579 --> 00:18:25.099
Muscle weakens, develops.
00:18:25.180 --> 00:18:30.379
Um babies may become unusually sensitive to sound, develop vision and hearing loss, seizures.
00:18:30.619 --> 00:18:35.019
It's pretty, unfortunately, it's pretty noticeable pretty quick.
00:18:35.339 --> 00:18:40.220
And as that disease progresses, the nervous system continues to deteriorate.
00:18:40.379 --> 00:18:48.539
And all that can be traced back to one, not one, but a mutation that shifted the reading frame of DNA.
00:18:48.700 --> 00:18:51.019
One tiny change in the genetic letters.
00:18:51.259 --> 00:18:59.180
And again, you have one example where it's like just changes your blood type, another frame shift, and it's a completely different outcome.
00:18:59.420 --> 00:18:59.740
Yeah.
00:18:59.980 --> 00:19:06.139
So, you know, there's honestly it's still because of the more extreme situations, right?
00:19:06.299 --> 00:19:11.660
Scientists are so actively studying frame shift mutations to understand them.
00:19:11.899 --> 00:19:18.220
And they're not well, because sometimes it depends, like frame shifts can be like just a couple or it can be giant sections.
00:19:18.460 --> 00:19:19.500
Yep, giant sections.
00:19:19.660 --> 00:19:26.700
And so now we know so well about how it works, now they're actively trying to fix them.
00:19:26.859 --> 00:19:31.980
So it's like, okay, we kind of get how it works, like we get you're gonna be shifting it, we understand that.
00:19:32.139 --> 00:19:33.899
But now how can we fix it?
00:19:34.059 --> 00:19:43.740
And researchers are working on gene editing technologies, like we've talked about CRISPR several times before, and that can actually target specific mutations and tie to DNA.
00:19:43.899 --> 00:19:50.779
And one major goal with CRISPR is figuring out how to correct frame shift mutations before they cause a severe disease.
00:19:50.940 --> 00:19:55.579
So it's basically like as we see that this is going to be happening, can we go in there?
00:19:55.660 --> 00:20:33.199
Because again, if your DNA is always duplicating, can we go in there and hurry up and fix it?
00:20:33.359 --> 00:20:39.279
And then that way, as it's reproducing and your DNA is duplicating, it it you know fixes itself.
00:20:39.439 --> 00:20:59.199
And that's crazy, crazy wow, because when you think about what that means, we're talking about like humans learning how to you know edit actual instruction manuals of life, and that really has like some positive, it has some positive beneficial outcomes if done responsibly, right?
00:20:59.279 --> 00:21:06.159
Because anything that we throw at, you know, people can do a lot of harm or it can do a lot of a lot of good.
00:21:06.479 --> 00:21:12.479
So yeah, so that's just brief overview on the first mutation, which is frameshift.
00:21:13.759 --> 00:21:15.679
Yeah, frame shift is really crazy.
00:21:15.839 --> 00:21:24.639
So that leads directly into mine, which I actually just lumped two of mine together because insertion and deletion is really just the it's uh it's the flip side of the coin.
00:21:24.959 --> 00:21:25.119
Yeah.
00:21:25.359 --> 00:21:36.639
Um so the outcomes might be different depending on what's been studied, but in general, insertion and deletion typically just leads to frame shift.
00:21:36.879 --> 00:21:51.679
But basically insertion is a base pair is added where it doesn't belong, or like so insertion is when you add in things that don't belong, and a deletion is when you delete when things are deleted from the sequence.
00:21:51.919 --> 00:22:01.839
So like Katie was saying, if it's just a single base pair that's added in, that causes a frame shift, or if it's two that are added in, it causes a frame shift.
00:22:02.319 --> 00:22:16.559
If three are added in, like Katie was saying, if it's divisible by three, three, six, nine, if like a group of those are added in, it doesn't cause a frame shift, but it can create just an entirely new amino acid.
00:22:16.879 --> 00:22:25.919
So throwback to biology and genetics of when DNA is being read, it's being read in sets of threes.
00:22:26.319 --> 00:22:31.199
Every set of three creates an amino acid, lots of amino acids create a protein.
00:22:32.000 --> 00:22:33.279
Proteins build who we are.
00:22:33.439 --> 00:22:33.599
Okay.
00:22:33.759 --> 00:22:36.000
So like build, build, build, build, build.
00:22:36.399 --> 00:22:44.399
So if an entirely new amino acid is being created, I mean, sometimes it's good and sometimes it's bad.
00:22:44.639 --> 00:22:45.039
Yeah.
00:22:45.519 --> 00:22:47.839
So what are the outcomes?
00:22:48.079 --> 00:22:58.159
One, they can totally jack up the amino acids being formed, which can change the subsequent protein that's being read, especially if it causes translation to stop early.
00:22:58.319 --> 00:22:59.679
Translation is what happens.
00:22:59.759 --> 00:23:02.239
There are little things on your DNA transcribing it.
00:23:02.319 --> 00:23:04.399
I like to think about it as like little tiny people with a typewriter.
00:23:04.559 --> 00:23:07.359
So and all the ticker, the little tapes just coming off.
00:23:07.519 --> 00:23:07.679
Yeah.
00:23:07.919 --> 00:23:09.039
It's creating new things.
00:23:09.119 --> 00:23:13.039
They're just translating your DNA and making lots and lots of proteins.
00:23:13.359 --> 00:23:14.879
So what we want to happen.
00:23:15.439 --> 00:23:20.639
Is that process to just not stop, at least in chunks, to make these proteins?
00:23:21.199 --> 00:23:27.039
But if something is wonky, let's say these little guys who are reading your DNA, they're like, this doesn't make any sense.
00:23:27.199 --> 00:23:27.839
Forget this.
00:23:27.919 --> 00:23:29.039
I'm not reading anymore.
00:23:29.199 --> 00:23:30.079
They just stop.
00:23:30.639 --> 00:23:36.159
So then you have a really jacked-up protein because it's not as long as it's supposed to be.
00:23:36.319 --> 00:23:43.679
I want to give some examples of, well, a good prop, like, you know, we a lot of times people talk about mutations as being inherently bad.
00:23:43.759 --> 00:23:46.559
And what we've said is that it doesn't necessarily have to be.
00:23:46.799 --> 00:23:47.039
Yeah.
00:23:47.279 --> 00:23:54.959
So an example um a beneficial, because there are beneficial the entire human race was made because of mutations, right?
00:23:55.039 --> 00:24:00.559
Like if you can subscribe to any form of evolution, we got here through mutation.
00:24:00.879 --> 00:24:03.439
Um so like or adaptations of anything.
00:24:03.519 --> 00:24:09.199
Like even it, let's just say, even if you don't believe at all in evolution, don't let any form of change.
00:24:09.439 --> 00:24:11.119
Yeah, is is this mutation.
00:24:11.439 --> 00:24:12.479
100% this, yeah.
00:24:12.799 --> 00:24:13.279
Yeah.
00:24:13.599 --> 00:24:30.879
But it more specifically, I found a cool one, which is uh a 32 base pair deletion in a specific gene known as CCR5, it it removes one of the receptors from a white blood cell, which makes you basically immune to HIV.
00:24:31.439 --> 00:24:32.399
Interesting.
00:24:32.719 --> 00:24:33.039
Yeah.
00:24:33.199 --> 00:24:34.959
So like that'd be a great mutation to have.
00:24:35.279 --> 00:24:36.639
You just can't get HIV.
00:24:36.879 --> 00:24:37.279
Yeah.
00:24:37.519 --> 00:24:38.959
Uh and that's one.
00:24:39.119 --> 00:24:42.799
There's no are they doing anything with that to like make it?
00:24:42.959 --> 00:24:43.919
I didn't get a chance to look at it.
00:24:44.000 --> 00:24:44.479
Okay, okay, okay.
00:24:44.719 --> 00:24:45.279
Totally should have.
00:24:45.439 --> 00:24:47.439
I just literally just looked it up.
00:24:47.599 --> 00:24:51.759
Because I was like, oh, I should have talked more about beneficial stuff, not just the doom and gloom.
00:24:52.000 --> 00:24:52.319
Yeah.
00:24:52.479 --> 00:24:54.719
Um, but surely, right?
00:24:54.879 --> 00:24:57.599
Because I guess you'd have to do some gene splicing here.
00:24:57.679 --> 00:25:00.479
I mean, like, right, the future is gene splicing.
00:25:01.279 --> 00:25:03.199
But comes with inherent risks.
00:25:03.359 --> 00:25:13.359
I was just reading an article that they found the first ever case of a brain tumor caused by gene splicing, which is so like but it might save your life.
00:25:13.519 --> 00:25:16.000
And the brain tumor they removed, the person was fine.
00:25:16.079 --> 00:25:19.199
It's just like yes, messing with your body can cause cancer.
00:25:19.359 --> 00:25:19.599
Yeah.
00:25:20.079 --> 00:25:20.639
Definitely.
00:25:21.199 --> 00:25:24.799
So was it cancer or was it just like a but like was it just a benign tumor?
00:25:25.039 --> 00:25:25.839
Oh, yeah, yeah, you're right.
00:25:25.919 --> 00:25:28.000
I guess it was just like cancer is growing up.
00:25:28.719 --> 00:25:28.879
Yeah.
00:25:29.039 --> 00:25:29.359
Yeah.
00:25:29.519 --> 00:25:30.479
I didn't read enough.
00:25:30.639 --> 00:25:38.799
But yeah, so whether or not it was benign or not, messing with genes can cause issues, but if we could figure out how to harness it, we could do some crazy cool things.
00:25:38.959 --> 00:25:39.519
Yeah.
00:25:39.839 --> 00:25:47.359
One though that's not so beneficial, but like on a scale of like, I I chose to focus on ones that didn't cause death.
00:25:47.519 --> 00:25:47.759
Yeah.
00:25:48.000 --> 00:25:50.079
Because I just didn't want to read too much about it.
00:25:50.159 --> 00:25:51.119
It was too depressing.
00:25:51.679 --> 00:26:00.719
Um lots of genetic issues have their own help groups and own support groups and like, you know, advocacy groups.
00:26:00.879 --> 00:26:02.000
You should totally look it up.
00:26:02.159 --> 00:26:07.359
But this one I wanted to talk about is the deletion of part of paternal chromosome 15.
00:26:07.599 --> 00:26:10.639
So remember, you get two chromosomes, one from your dad, one from your mom.
00:26:10.719 --> 00:26:12.879
This is a problem with your dad's number 15.
00:26:13.279 --> 00:26:15.679
It's Prater Prater Villi syndrome.
00:26:16.000 --> 00:26:17.839
It's spelled Willy, but it's villi.
00:26:18.639 --> 00:26:24.479
And the typically, so 60% of the time, it's caused by a deletion.
00:26:24.639 --> 00:26:27.599
There are other things because mutations can happen for lots of reasons.
00:26:27.839 --> 00:26:27.919
Yeah.
00:26:29.119 --> 00:26:31.119
But deletion is usually the problem.
00:26:31.359 --> 00:26:34.719
And basically what happens is it makes your hypothalamus not work correctly.
00:26:34.879 --> 00:26:38.159
And your hypothalamus does a lot of things in your brain.
00:26:38.479 --> 00:26:44.959
Like so as infants, it causes poor muscle tone, poor sucking reflex, and distinct facial features.
00:26:45.119 --> 00:26:48.159
So like just like a hard time growing and thriving.
00:26:48.639 --> 00:27:00.079
Um, and then as they get older, there's usually there's a lot of symptoms, but one of them, some of them are delayed puberty, poor growth, behavior issues, cognitive issues.
00:27:00.239 --> 00:27:03.919
And the worst one I think is being hungry all the time.
00:27:04.159 --> 00:27:05.919
Oh, that would be horrible.
00:27:06.239 --> 00:27:09.119
So imagine the hell of never being full.
00:27:10.639 --> 00:27:12.799
They literally lack the ability to be full.
00:27:13.119 --> 00:27:19.359
Cause uh, but I mean, okay, just mentally, the the strain and stress that that would put on, you know what I mean?
00:27:20.399 --> 00:27:21.759
You'd always be thinking of food.
00:27:22.000 --> 00:27:23.119
Yeah, yeah, man.
00:27:23.359 --> 00:27:25.679
Cause like when I'm hungry, like Katie, that's it.
00:27:25.919 --> 00:27:28.079
Like I'm eating every two hours and I'm angry.
00:27:28.159 --> 00:27:29.599
Like Yeah, Laura gets hangry.
00:27:29.679 --> 00:27:30.879
Yeah, Laura definitely gets angry.
00:27:31.359 --> 00:27:32.399
Hangry 24-7.
00:27:32.719 --> 00:27:33.679
I bet they're different people.
00:27:33.919 --> 00:27:36.159
Like, can you imagine the personality shift?
00:27:36.319 --> 00:27:36.479
Yeah.
00:27:36.799 --> 00:27:37.599
They're full.
00:27:37.839 --> 00:27:38.079
Yeah.
00:27:38.239 --> 00:27:40.719
So what happens is they crave food all the time.
00:27:40.959 --> 00:27:45.279
Not only do they crave food all the time, but they actually have a lower metabolic rate.
00:27:45.759 --> 00:27:46.399
Um, yeah.
00:27:46.639 --> 00:27:49.839
Both of which can learn to lead to severe obesity.
00:27:50.000 --> 00:27:50.239
Yeah.
00:27:50.479 --> 00:27:52.159
And all the issues that come with that.
00:27:52.399 --> 00:27:57.839
So, like, I mean, these people have to go through serious therapy to learn how to control cravings.
00:27:57.919 --> 00:28:00.079
When they're little, people have to like lock food up.
00:28:00.319 --> 00:28:05.439
They've been known known to hoard food, eat frozen food, and even eat garbage because they're so freaking hungry.
00:28:06.239 --> 00:28:06.879
Yeah.
00:28:07.679 --> 00:28:09.839
Well, their brain is telling them that they're hungry.
00:28:09.919 --> 00:28:11.119
Like their stomach is physically.
00:28:11.519 --> 00:28:12.639
They're not actually starving.
00:28:12.879 --> 00:28:13.039
Yes.
00:28:13.599 --> 00:28:14.319
They just can't.
00:28:14.479 --> 00:28:16.079
They never feel satiated.
00:28:16.399 --> 00:28:20.479
Um, so although it doesn't cause death, there are serious complications.
00:28:20.959 --> 00:28:21.119
Yeah.
00:28:21.359 --> 00:28:24.000
One, obesity and like mental toll.
00:28:24.159 --> 00:28:26.639
But it's almost like sterility and osteoporosis.
00:28:26.959 --> 00:28:35.119
It's almost like a secondary, like death is like a secondary because because of how much of the symptoms it's a secondary cause of totally, you know.
00:28:35.279 --> 00:28:35.679
Yeah.
00:28:36.000 --> 00:28:41.439
And so it's thought to be between one in 10,000 to one in 30,000 births.
00:28:41.759 --> 00:28:46.479
So thankfully not a ton, but my man, it would be horrible.
00:28:46.559 --> 00:28:49.599
I might thoughts go out to anybody that has it.
00:28:49.839 --> 00:28:50.000
Yeah.
00:28:50.239 --> 00:28:51.759
Yeah, that would be a tough one.
00:28:52.479 --> 00:28:55.359
And then on the flip side, insertion.
00:28:55.679 --> 00:29:04.959
So in this gene called the FMR1 gene, which is located specifically on the X chromosome, which is the one you get from your mom and you get one from your dad.
00:29:05.199 --> 00:29:06.719
If you're a girl, you get two.
00:29:06.879 --> 00:29:09.039
If you're a girl, you get one if you're a guy.
00:29:09.279 --> 00:29:12.159
There's an expanded CGG triplet.
00:29:12.239 --> 00:29:16.239
So those three little base pairs, CGG, it happens multiple times.
00:29:16.399 --> 00:29:19.679
Um, and that causes fragile X syndrome.
00:29:20.000 --> 00:29:20.239
Yeah.
00:29:20.479 --> 00:29:21.599
I remember a lot of these.
00:29:21.679 --> 00:29:23.199
Once you say them, I'm like, oh yeah.
00:29:23.359 --> 00:29:30.000
I don't want to get, I don't want to look too excited, but any any of my facial expressions is like, hey, I remember something from that horror.
00:29:30.399 --> 00:29:46.479
Recognize that term that we're fragile, fragile X syndrome basically turns off or silences the FMR1 gene, which is responsible for creating these special proteins that build nerve synapses, so the things that go between nerves.
00:29:46.799 --> 00:29:55.119
Um and because of these this insertion, it makes the X chromosome look all wonky and look broken or really fragile.
00:29:55.279 --> 00:30:03.119
Um and so the symptoms of this are intellectual disability, anxiety, depression, and OCD, behavioral issues, and specific physical traits.
00:30:03.359 --> 00:30:09.039
These people are at a higher risk for many health issues, including dementia, migraines, chronic pain, and seizures.
00:30:09.119 --> 00:30:12.079
So all problems with like nerves because of nerve synapses.
00:30:12.319 --> 00:30:18.000
And unfortunately, is it is a dominant, it is a dominant trait.
00:30:18.239 --> 00:30:21.279
So it's if you've got it on an ex, you're gonna have it.
00:30:21.439 --> 00:30:22.639
And it's sex linked.
00:30:22.879 --> 00:30:31.599
So that means that if you're a dude, you're way more likely to have it than a girl because as soon as you get one ex, that's it.
00:30:31.679 --> 00:30:36.479
But even if you are a girl, if you've got one, even just one broken ex, you'll have it.
00:30:37.199 --> 00:30:41.519
So it's about one in 7,000 males and one in 11,000 females.
00:30:42.159 --> 00:30:48.799
Apparently, it's like one of the most common reasons for genetic intellectual disabilities.
00:30:50.479 --> 00:30:59.599
So beneficial insertions and deletions happen, but there's also some really terrible things, and even worse than this.
00:30:59.679 --> 00:31:04.319
But it's just it but again, it goes back to just how wild it is of like so.
00:31:04.399 --> 00:31:07.679
For our viewers on YouTube, you will see I have a new shirt on.
00:31:07.839 --> 00:31:14.719
It's because I was giving my son his lasagna and I flopped it out on the plate, and it splattered.
00:31:15.279 --> 00:31:16.399
Uh new shirt.
00:31:18.079 --> 00:31:18.239
Right?
00:31:18.319 --> 00:31:19.919
Yep, all over my shirt.
00:31:20.159 --> 00:31:21.759
Anyway, we are good.
00:31:21.839 --> 00:31:31.679
Okay, so what I was gonna say was that yes, it's like it's horrible, but at the same time, it when things go wrong, it can go very, very wrong.
00:31:31.759 --> 00:31:36.719
But at the same time, you gotta remember our bodies are doing this a bajillion times like times.
00:31:37.119 --> 00:31:37.359
Yeah.
00:31:37.599 --> 00:31:40.000
And so it's um it's insanely impressive.
00:31:40.319 --> 00:31:41.759
No, but it's not constantly happening.
00:31:42.079 --> 00:31:48.079
Well, and that it is could be constantly happening, but that the so-so wrong is so so rare.
00:31:48.799 --> 00:31:49.519
Yeah, yeah.
00:31:49.599 --> 00:31:52.559
That yeah, like I think it's important to keep that in perspective.
00:31:53.279 --> 00:32:04.319
Yes, that like, hey, this is going on thousands of times, and it's insane that our bodies can even get it right this many times all the time for the most at all because of the process.
00:32:04.399 --> 00:32:11.199
So that is really, really it makes you appreciate the process that you literally don't see.
00:32:11.279 --> 00:32:12.959
And we didn't know for thousands of years.
00:32:13.039 --> 00:32:14.079
We had no idea it even exists.
00:32:14.319 --> 00:32:22.479
Yeah, it's literally like straight up magic or like like it is crazy when you really think about it.
00:32:22.639 --> 00:32:25.839
The fact is like we're not just single-celled organisms here.
00:32:25.919 --> 00:32:32.799
We are making billions and trillions of proteins and like decisions a day that's a time it's just right.
00:32:33.119 --> 00:32:34.559
It's just right, which is crazy.
00:32:35.439 --> 00:32:35.759
Yeah.
00:32:36.159 --> 00:32:36.639
Alrighty.
00:32:36.799 --> 00:32:40.639
So my next one then is a duplication.
00:32:40.879 --> 00:32:41.359
All right.
00:32:41.599 --> 00:32:41.919
Okay.
00:32:42.319 --> 00:32:46.879
So this one kind of I always gotta start with an example.
00:32:47.039 --> 00:32:54.000
That's just how my brain works, but it's a DNA's equivalent of hitting copy and paste too many times.
00:32:54.159 --> 00:32:54.399
All right.
00:32:54.639 --> 00:32:56.079
Which is kind of like insertion.
00:32:56.239 --> 00:32:56.479
Yeah.
00:32:56.719 --> 00:32:58.959
Or like yeah, yeah, yeah.
00:32:59.199 --> 00:33:05.279
A duplication mutation happens when a section of DNA gets copied more than once, exactly what it sounds like.
00:33:05.439 --> 00:33:08.879
Sometimes it's a tiny section, sometimes it's an entire gene.
00:33:08.959 --> 00:33:12.799
Sometimes it can even involve huge chunks of chromosomes getting repeated.
00:33:12.879 --> 00:33:15.119
So it could be a variety of different things.
00:33:15.359 --> 00:33:24.000
And unlike a frameshift mutation where the instructions kind of get all scrambled up, duplication mutation still keeps the original instruction.
00:33:24.239 --> 00:33:32.079
So the cat ate the rat, it's just the cat ate the rat, the cat ate the rat, the cat ate the rat more so when it should just be one sentence.
00:33:32.159 --> 00:33:33.919
Now it's like three or four.
00:33:34.159 --> 00:33:39.839
Um, so I mean, obviously, like it sounds for the most part harmless, right?
00:33:39.919 --> 00:33:44.399
Like if one cookie is good, obviously 12 cookies are better situation.
00:33:44.719 --> 00:33:45.039
Yeah.
00:33:45.279 --> 00:33:56.000
But on but unfortunately, that's deaf that's not always the case because cells, just like any honestly, anything in biology operates on in a balance, right?
00:33:56.079 --> 00:33:58.799
Proteins need to be produced in very specific amounts.
00:33:59.039 --> 00:34:05.439
Too little can cause problems, too much can cause completely different problems, just like in an ecosystem.
00:34:05.599 --> 00:34:09.280
Too many of one species, problem too many, too many, too little.
00:34:09.360 --> 00:34:11.199
It it's all about balance.
00:34:11.440 --> 00:34:19.840
So duplication mutations can create all sorts of odd outcomes depending on what gets copied and how many extra copies are actually there.
00:34:20.159 --> 00:34:22.559
Some of them can be surprisingly helpful.
00:34:22.719 --> 00:34:31.920
One of the one examples that I do remember this from our genetics class was the AMI-1 gene, AMY1, the number gene.
00:34:32.159 --> 00:34:42.880
And this gene helps uh produce the salivary alamase, which is the enzyme in our saliva that starts to break down starches while we're still chewing food.
00:34:43.200 --> 00:34:49.760
So before your food even reaches your stomach, our body is already going, excellent, potatoes.
00:34:49.920 --> 00:34:51.600
Like, let's let us begin.
00:34:51.760 --> 00:34:52.720
And that's my head.
00:34:52.800 --> 00:34:54.160
Like, I begin.
00:34:54.400 --> 00:35:01.200
Like, because again, my brain, and I have to use potatoes because that's my by far my favorite starch, but I'm also German.
00:35:01.440 --> 00:35:04.640
And so there's just something in me that I'm like, oh my god, potatoes.
00:35:04.720 --> 00:35:06.960
Give me any form of potato, and I'm a happy potato.
00:35:07.280 --> 00:35:08.160
Like most of us are like that.
00:35:08.320 --> 00:35:09.200
Yeah, 100%.
00:35:09.840 --> 00:35:10.080
God.
00:35:10.400 --> 00:35:11.440
Pickles and potatoes.
00:35:11.680 --> 00:35:20.960
I I forgot though, whenever I was re-looking all this up, that humans, not all of us have the same numbers of copies of this gene, right?
00:35:21.200 --> 00:35:23.120
Some people have more copies than others.
00:35:23.920 --> 00:35:28.960
Yeah, because uh duplication mutations over time created extra versions of the gene.
00:35:29.120 --> 00:35:36.000
And populations historically, this historically like starch-heavy diets, like Laura and I were like, Oh, I feel like that's everybody.
00:35:36.160 --> 00:35:41.760
Honestly, down here, people eat potatoes, but it's not like a staple of the diet.
00:35:41.840 --> 00:35:45.920
Because again, where I'm originally from in Pittsburgh, it's cold.
00:35:46.160 --> 00:35:58.800
It's very much so like German, Polish, you know, we have our porojis, we have our lacos, we have so we have the very filling foods because it's cold and your body needs to stay warm, it needs that extra energy.
00:35:59.040 --> 00:36:11.280
We're down here in Texas, because it's so dang hot, if you're eating foods that make you feel heavy, you just like you just feel miserable because it's 120 freaking degrees in the summer.
00:36:11.360 --> 00:36:16.800
So you eat tacos that are lightweight, like the light filling, so you don't need as many.
00:36:17.040 --> 00:36:30.800
So this heavy surge diets, things like rice, wheat, potatoes, tend to those populations tend to have more copies of the Amy 1 mutation, which just means that the body's just thinking about it.
00:36:31.120 --> 00:36:32.000
Potatoes, man.
00:36:32.080 --> 00:36:36.640
I'm just a potato and a pickle girl, like through and through.
00:36:37.200 --> 00:36:39.600
Um the most Pittsburgh thing ever.
00:36:39.760 --> 00:36:41.120
Pickle girls potatoes.
00:36:41.520 --> 00:36:42.320
Dude, I can't.
00:36:42.400 --> 00:36:44.480
I am I can't I have Pittsburgh blood.
00:36:44.960 --> 00:36:47.200
I haven't met a form of potato I don't like.
00:36:47.440 --> 00:36:48.560
Oh, me either.
00:36:48.720 --> 00:36:52.480
I we I can make a podcast episode just on potatoes.
00:36:52.640 --> 00:36:53.360
On just potatoes.
00:36:53.680 --> 00:36:55.600
On just potatoes and all their functions.
00:36:55.680 --> 00:36:56.800
I would just be I would be so happy.
00:36:56.880 --> 00:36:57.440
We'll doggy.
00:36:59.600 --> 00:37:01.200
Yeah, just just potatoes.
00:37:01.680 --> 00:37:03.280
And pumpkins, we'll just do potatoes.
00:37:03.440 --> 00:37:04.640
Potatoes, yeah.
00:37:04.960 --> 00:37:10.080
So sometimes evolution bile, like basically it's just like, hey, this is actually beneficial.
00:37:10.240 --> 00:37:18.240
You have a food, you know, this population, especially, you know, in Europe wherever it's cold, these groups are like, hey, these starchy foods actually do us well.
00:37:18.320 --> 00:37:22.240
It helps us, you know, you gotta have food and stay warm.
00:37:22.480 --> 00:37:32.320
And so the body's kind of shifted, started shifting over time and provided more of that, like the salivatory protein in your saliva to help break it down.
00:37:32.480 --> 00:37:35.520
And so it's wildly beneficial for groups.
00:37:35.600 --> 00:37:38.160
So I mean, that can be a benefit beneficial.
00:37:38.400 --> 00:37:48.320
Some of the one of the more extreme examples, though, where duplication can go very, very wrong, is called Charlet Marie tooth disease type 1A.
00:37:48.800 --> 00:37:57.600
Usually shortened to, yeah, usually shortened to CMT1A, because that everything else is just a mouthful to say.
00:37:57.920 --> 00:38:04.080
But this condition is caused commonly caused by duplication of a gene called PMP22.
00:38:04.160 --> 00:38:11.760
And PMP22 helps maintain myelin, which is the protective coating wrapped around nerves.
00:38:11.920 --> 00:38:18.960
So think of myelin kind of like the insulation wrapped around electrical wiring, right?
00:38:19.040 --> 00:38:24.080
It helps the nerve signal and travel quickly and efficiently throughout the body.
00:38:24.480 --> 00:38:37.680
But, you know, there are also this is kind of one of those examples where duplication mutations kind of get sneaky because you think, oh, extra copies of like a helpful gene could make the like would it make it work even better?
00:38:37.840 --> 00:38:48.240
And unfortunately, no, because again, biology is built entirely around the concept of like too much of a good thing isn't always a good thing, if that makes sense.
00:38:48.560 --> 00:38:49.280
It has to be just right.
00:38:49.360 --> 00:38:51.680
It's gold your body is golden clocks.
00:38:52.080 --> 00:38:52.640
100%.
00:38:53.280 --> 00:39:03.840
So people with CMT1A have an extra copy of the PM PMP22 gene, which leads, like we said, to too much of that protein being produced.
00:39:04.000 --> 00:39:09.920
And instead of helping nerves, that imbalance actually disrupts the myelin and damages nerve signaling over time.
00:39:10.240 --> 00:39:18.960
So people with CMT1A can experience muscle weakness, loss of sensation in the hands and feet, balance problems, difficulty walking, and so on.
00:39:19.120 --> 00:39:26.080
And so, again, like this can just be like one extra copy, and and that's what causes this.
00:39:26.240 --> 00:39:35.040
To me, again, this duplication one, just like all of them, it's just crazy how one little duplication in one spot, same thing as the last one I talked about, it causes like something very mild.
00:39:35.120 --> 00:39:38.960
Like, okay, you salivate more fashion for your starch food.
00:39:39.200 --> 00:39:49.920
And then this type of duplication like is too much of a coating, and it breaks down your your nerves essentially, or it prohibits them from communicating as effectively.
00:39:50.080 --> 00:40:01.440
And so, scientists they're definitely studying the duplication mutations intensely because they play such a huge role in human disease development, the evolution, and cancer research.
00:40:01.760 --> 00:40:10.480
So they're really right now trying to understand something called gene dosage, which is basically the question of how many copies of a gene is too much.
00:40:10.720 --> 00:40:17.840
Because again, sometimes, sometimes that duplication is like, okay, like again, three cookies is okay.
00:40:18.240 --> 00:40:21.440
12, too much, but like how much is too much?
00:40:21.600 --> 00:40:27.280
Is it 12 or is it all depends on how much it's bending your protein, like it makes a certain shape.
00:40:27.440 --> 00:40:30.880
It's like it's basically creating an origami.
00:40:30.960 --> 00:40:35.600
If you add in too many folds or not enough folds, it doesn't make the animal you're trying to make.
00:40:35.840 --> 00:40:36.800
Exactly, exactly.
00:40:36.880 --> 00:40:40.240
And so that's kind of what scientists are really working on right now with that.
00:40:40.480 --> 00:40:56.720
Um, you know, and again, using a lot of the same sort of technologies and studying this, because again, a little bit is okay, too much is too much, and just trying to find that line, and then hey, can we fix, can we reverse, can we cut this out?
00:40:56.960 --> 00:40:59.440
If and and like, where is it gonna be too much?
00:40:59.520 --> 00:41:04.480
So if 12 cookies is too many, if we backed it down to six, like is that okay?
00:41:04.640 --> 00:41:10.160
Like, is that an okay can your body function with some of these conditions that you end up getting from duplication?
00:41:10.320 --> 00:41:14.000
So, so yeah, that's all I have for for my second one.
00:41:15.120 --> 00:41:15.760
Interesting.
00:41:16.000 --> 00:41:27.280
So just my other one and the most common form of mutation, I was gonna start with this one, but insertion and deletion just added so well into yours that I was like, I just gotta continue it on because that's frame shift.
00:41:27.840 --> 00:41:31.120
But the most common type of mutation is substitution.
00:41:31.680 --> 00:41:36.000
So this one it's just a switchy, a flippity-flop, a switchy switch.
00:41:36.080 --> 00:41:39.200
It's just when one base pair is replaced by another one.
00:41:39.440 --> 00:41:42.560
Although there are two types of substitutions.
00:41:42.800 --> 00:41:49.920
There is a transition, so that is when hold on, I gotta get this right.
00:41:51.120 --> 00:41:56.080
Okay, so you know how I said that there's these four letters, A, G, C, T.
00:41:56.160 --> 00:41:59.760
And I said that A and T always go together, and G and C always go together.
00:42:00.240 --> 00:42:06.960
Now a transition, and like okay, imagine two of them are always on the top and two of them are always on the bottom.
00:42:07.680 --> 00:42:12.560
A transition is when the same two on the top switch with each other.
00:42:12.720 --> 00:42:16.080
Okay, so that would be an A and a G flip or a T and a C flip.
00:42:16.640 --> 00:42:21.200
So it's just transition from one spot to the other.
00:42:21.840 --> 00:42:25.920
Then there's transversion, which is when they completely flip sides.
00:42:26.240 --> 00:42:33.440
So when an A and a G pair up, which they don't ever do, or a T and a C pair up and they never do.
00:42:33.760 --> 00:42:43.600
Um, so two different types of substitutions causing different issues, but either switching with your partner side by side, do si do, or across the room.
00:42:43.760 --> 00:42:47.680
So they just again again, it's just like it's so mind of your genes.
00:42:47.920 --> 00:42:53.600
But it's so again, it goes back to it's so mind-boggling to me that we're not just like goop mush.
00:42:53.680 --> 00:43:07.120
Like the fact that for the most part, humans, we are evolved as we are to do what we can do, and that this process has to work perfectly every single time, all the time, is just it's nuts to me.
00:43:07.440 --> 00:43:07.760
Yeah.
00:43:08.000 --> 00:43:13.920
I mean, I think that's where some of like my my faith comes in because I was I'm like craziness, yeah.
00:43:14.320 --> 00:43:15.120
Perfection.
00:43:15.360 --> 00:43:15.520
Yeah.
00:43:15.760 --> 00:43:17.840
Um someone's got OCD.
00:43:18.160 --> 00:43:25.760
Like so the outcomes we also failed to mention, I think.
00:43:25.920 --> 00:43:32.080
So there's beneficial mutations, there's the bad when it goes bad, but there's also just silent mutations.
00:43:32.240 --> 00:43:34.480
So sometimes the outcome is just nothing.
00:43:34.720 --> 00:43:35.040
Nothing.
00:43:35.360 --> 00:43:35.680
Just nothing.
00:43:35.760 --> 00:43:36.080
Yeah.
00:43:36.240 --> 00:43:39.680
It's literally the same outcome before the switch ever happened.
00:43:39.840 --> 00:43:42.720
Sometimes it just works out that it's the exact same thing.
00:43:42.880 --> 00:43:45.280
The person reading it was like, they didn't get messed up.
00:43:45.360 --> 00:43:48.800
They just kept kept reading and made the same end product.
00:43:48.880 --> 00:43:55.440
Kind of like sometimes you see those sentences online where you're like supposed to read it and you didn't notice that one word was wrong.
00:43:55.760 --> 00:43:57.360
Welcome to fucking ADHD.
00:43:57.680 --> 00:43:57.760
Right.
00:43:57.840 --> 00:43:57.920
Yeah.
00:43:58.080 --> 00:43:58.640
Like my brain's.
00:44:00.560 --> 00:44:04.080
Yeah, my brain doesn't even catch most of that because it just filling in the blanks.
00:44:04.160 --> 00:44:06.880
It's like, oh, it just assumes that's how it's supposed to be.
00:44:06.960 --> 00:44:07.040
Yeah.
00:44:07.360 --> 00:44:10.000
I make a lot of assumptions too when reading directions and things like that.
00:44:10.080 --> 00:44:11.600
Like I'm like, yep, got it.
00:44:11.920 --> 00:44:12.240
Yep.
00:44:13.040 --> 00:44:14.560
Same outcome, usually.
00:44:14.800 --> 00:44:17.360
And then there, so that's when nothing happens.
00:44:17.520 --> 00:44:25.360
And then a there's a miss sense mutation, which is when new code is created that can impact formation.
00:44:25.840 --> 00:44:28.800
So that's when these frame shifts hap.
00:44:29.200 --> 00:44:33.920
That's when what is read off is changed.
00:44:34.480 --> 00:44:34.640
Okay.
00:44:35.120 --> 00:44:36.960
But most of it's still there.
00:44:37.600 --> 00:44:39.760
Like it's just all jumbled up.
00:44:40.080 --> 00:44:40.400
Okay.
00:44:40.560 --> 00:44:45.360
And then there's nonsense mutations, which is stopping translation.
00:44:45.520 --> 00:44:49.760
That's when the the reader is like, I literally got this makes no sense at all.
00:44:50.080 --> 00:44:50.720
I'm done.
00:44:50.960 --> 00:44:51.200
Yeah.
00:44:51.360 --> 00:44:57.440
So they stop translating prematurely, which can have major impacts and because the protein's just not even there.
00:44:57.680 --> 00:44:58.080
Yeah.
00:44:58.400 --> 00:45:07.360
Time where it's beneficial that a substitution happens, probably my favorite example is lactase persistence, which allows us to keep drinking milk.
00:45:07.600 --> 00:45:12.000
And if there's one thing I love almost as definitely as much as potatoes, it's milk.
00:45:12.640 --> 00:45:17.200
See, I've I've gotten away, and again, I think it's like A heat thing I've gotten away from milk.
00:45:17.440 --> 00:45:21.520
Cheese, however, that's like a no-going nowhere.
00:45:21.600 --> 00:45:22.000
Yeah, yeah.
00:45:22.160 --> 00:45:23.520
Bring me all the dairy.
00:45:23.680 --> 00:45:31.440
When I went dairy free for one month for the baby just to see if it would make any difference, I was like, I never realized that this is literally probably my biggest food group.
00:45:31.760 --> 00:45:34.320
Cheese isn't everything, and milk isn't everything.
00:45:34.480 --> 00:45:34.720
Yeah.
00:45:34.880 --> 00:45:36.240
I miss a good glass of milk.
00:45:36.400 --> 00:45:42.880
So lactase persistence, there has like over time, like humans weren't always able to drink milk forever.
00:45:43.440 --> 00:45:47.520
Because all the other animals cut it off after infancy and then you become lactose intolerant.
00:45:47.680 --> 00:45:54.560
So, like those of us that still have lactase persistence, that's all because of some substitutions that happen, a whole bunch of them.
00:45:54.800 --> 00:46:06.960
So, like single-base pears swapped with another one, uh usually most prominent in Europe, probably again because of like I don't know, dairy calories putting on weight needing to be because it's cold.
00:46:07.680 --> 00:46:08.160
Who knows?
00:46:08.400 --> 00:46:11.600
But a beneficial mutation that allowed us to keep eating dairy.
00:46:12.240 --> 00:46:20.720
But another one that is both good and bad, because sometimes mutations can be both, is sickle cell anemia.
00:46:21.520 --> 00:46:33.440
Um so that is when the A and the T get flipped in the sequence that codes for hemoglobin, which is what carries the oxygen in your blood, and a completely new amino acid happens.
00:46:33.920 --> 00:46:36.240
So this is a a missense mutation.
00:46:36.480 --> 00:46:39.840
So it's a mixed up one, but it still works.
00:46:40.320 --> 00:46:43.840
So this impacts the way the protein folds and the overall shape of the blood cell.
00:46:43.920 --> 00:46:45.200
They're supposed to be round when they're full.
00:46:45.520 --> 00:46:50.480
There's blood cells are supposed to be round all the time, whether they have oxygen in them or not.
00:46:50.800 --> 00:47:03.360
But when the this particular blood cell with this mutation becomes deprived of oxygen, they clump together and they become sickle shaped, so like those crescent moons, which can interrupt blood flow and cause pain and fatigue.
00:47:03.920 --> 00:47:06.880
But on the flip side, it does make you mostly immune to malaria.
00:47:07.680 --> 00:47:08.000
Yeah.
00:47:08.560 --> 00:47:11.520
So win, not win.
00:47:11.600 --> 00:47:13.600
I mean, you can be in pain but not get malaria.
00:47:13.760 --> 00:47:17.520
So depending on where in the world you live, which isn't this.
00:47:18.800 --> 00:47:19.280
African Americans.
00:47:21.760 --> 00:47:28.240
Which also, I mean, like, depending too, like it probably was allowed to persist because there are some benefits to this.
00:47:28.400 --> 00:47:33.280
One, it doesn't it that it it's not always it's not necessarily fatal.
00:47:33.600 --> 00:47:33.760
Yeah.
00:47:34.000 --> 00:47:35.520
Although it can disrupt blood flow.
00:47:35.840 --> 00:47:36.000
Okay.
00:47:36.240 --> 00:47:37.760
So it can eventually become fatal.
00:47:38.000 --> 00:47:38.320
Yeah.
00:47:38.560 --> 00:47:43.280
Um but it's that is that the action clots of malaria.
00:47:44.000 --> 00:47:47.360
Yeah, but is that is that fatal because of the actual mutation?
00:47:47.440 --> 00:47:50.080
Or again, is that like fatal from secondary?
00:47:50.640 --> 00:47:51.200
You know what I mean?
00:47:51.280 --> 00:47:51.920
Like a secondary mutant.
00:47:52.160 --> 00:47:53.280
I mean, probably I don't know.
00:47:53.440 --> 00:47:59.920
If it I think it can cause clots, but yeah, if you're making it to reproductive age, you're able to pass this along.
00:48:00.080 --> 00:48:04.160
And then if you're immune to malaria, you're more likely to be able to pass on your genes.
00:48:04.400 --> 00:48:17.040
So like this has persisted because all of these mutations have persisted because they they either happen randomly or because we've never gotten rid of them because they're not too detrimental, like the lactase thing.
00:48:17.440 --> 00:48:28.560
So I just I just Googled it, and yes, it is, and I knew it was serious, but it is life-threatening because of some one thing that you didn't mention is it was because it it bec it gets sticky, like the blood.
00:48:29.120 --> 00:48:29.760
Right, they clump together.
00:48:30.080 --> 00:48:30.800
They clump together.
00:48:31.600 --> 00:48:45.200
Yeah, and that is that is more so the problem than anything, which can block blood flow, leading to fatal complications, acute chests, anything with your heart, strokes, organ, kidney failure, severe infections, and and those kind of things.
00:48:45.280 --> 00:48:48.560
So it is because of this, because of the stickiness, yeah.
00:48:48.960 --> 00:48:49.440
Yeah, yeah.
00:48:49.600 --> 00:48:52.480
So like a clotting problem and blood blood flow.
00:48:52.800 --> 00:48:53.680
Blood flow, yeah.
00:48:54.640 --> 00:49:02.240
So yeah, that substitution, anything from being able to eat and drink dairy to um sickle cell anemia.
00:49:02.640 --> 00:49:03.040
Yeah.
00:49:03.280 --> 00:49:08.320
Well, guys, I'm gonna wrap it up then with an inversion mutation, our last one, real quick.
00:49:09.040 --> 00:49:18.320
These are honestly one of the weirdest ones to visualize, at least for me, because the DNA itself doesn't necessarily disappear, it just flips it backwards.
00:49:18.960 --> 00:49:19.600
Oh, okay.
00:49:19.840 --> 00:49:30.400
So your chromosomes can can break and rotate a section of DNA like 180 degrees and then like jam it back into place if it needs to.
00:49:30.480 --> 00:49:30.640
Yeah.
00:49:31.120 --> 00:49:34.880
Little workers are like, put it back, put it back, and they just didn't realize that they did it wrong.
00:49:35.280 --> 00:49:35.920
Yeah, yeah.
00:49:36.160 --> 00:49:36.800
Who knew?
00:49:36.960 --> 00:49:37.520
Oh no.
00:49:38.080 --> 00:49:40.240
So imagine Yeah, right.
00:49:40.480 --> 00:49:49.840
So imagine if you had a DNA sequence that originally looked like A, B, C, D, E, F, G, an inversion would be A, B, E, D, C, F, G.
00:49:50.000 --> 00:49:54.080
So it just kind of like flip-flops a section of it, could be bigger or smaller.
00:49:54.400 --> 00:49:59.520
And so again, it's like the information is still technically there, but now part of it is reversed.
00:49:59.600 --> 00:50:09.040
And depending, yeah, depending on where that inversion happens, the effects can range from like something that's not noticeable at all to severe genetic diseases.
00:50:09.200 --> 00:50:15.840
And because genes don't just depend on the information itself, they also depend on order, orientation, timing, and regulation.
00:50:16.240 --> 00:50:20.720
Once again, biology is an organizational nightmare.
00:50:20.800 --> 00:50:24.640
It should be, but it's not, like, which is just it's just wild again.
00:50:24.960 --> 00:50:34.080
So, one famous example is something called 17, so 17Q21.31 inversion polymorphism.
00:50:34.240 --> 00:50:42.400
So that inversion occurs on chromosome 17, and so many carriers have no obvious symptoms whatsoever.
00:50:42.560 --> 00:50:48.880
So there's no consequences of this, no sudden urge like to really know what's going on.
00:50:49.120 --> 00:51:10.480
And scientists think some of the inversions like this may actually stick around the populations because they help preserve useful combinations of genes that actually end up doing working pretty well together, which is kind of interesting because it means something like evolution, like we talked about, sees a chunk of DNA flip backwards and it was like, well, that works, let's just leave it there.
00:51:10.720 --> 00:51:13.280
Yeah, let's just leave it there because it doesn't really do anything.
00:51:13.440 --> 00:51:34.160
So most people go through life having no idea they even have this with no symptoms until they get genetic testing, maybe probably for something completely different, and then they're like, oh hey, by the way, and that's like with me, so I have an autoimmune condition and the the whole MTFR thing, how my body doesn't break down everything as as well as it should.
00:51:34.320 --> 00:51:43.040
I had no idea that was even like I that was even a problem for me until I started getting some genetics testing done to figure out what the heck, like, why did Katie Omos die?
00:51:43.200 --> 00:51:47.360
Like, why is her body trying to trying to kill her out of nowhere?
00:51:47.600 --> 00:51:57.280
And so whenever they started doing all the testing for that, that's when I I started seeing some underlying things that I never would have known until I went through all that testing.
00:51:57.520 --> 00:52:09.120
One of the more extreme examples though of inversion is uh you already talked about blood, so hemophilia A, so hemoblood is a genetic disorder where the blood has trouble forming blood clots properly.
00:52:09.280 --> 00:52:11.600
So you can imagine the opposite of sickle cell.
00:52:11.760 --> 00:52:12.000
Yeah.
00:52:12.400 --> 00:52:16.320
So you can imagine how how the problems that could lead for that.
00:52:16.400 --> 00:52:19.520
And so Yeah, that was like a big problem with the royal families in Europe, right?
00:52:19.680 --> 00:52:20.080
Mm-hmm.
00:52:20.640 --> 00:52:21.600
Hemophilia.
00:52:21.840 --> 00:52:27.680
Yeah, and and it and it definitely is seen a lot more in some cultures that than than others.
00:52:27.920 --> 00:52:42.320
So the F8 gene contains instructions for making clotting the clotting factors, which is in this case, it's the factor V VII, the A, which is one of the major proteins your body uses to stop bleeding.
00:52:42.560 --> 00:52:52.240
So basically, when you get injured, your body, you know, launches this insanely complex biological chain reaction involving clotting factors working together to form a stable clot.
00:52:52.400 --> 00:52:56.640
And your blood is basically running emergency repair constantly.
00:52:56.880 --> 00:53:03.680
But whenever you have that inversion mutation, part of the F8 gene gets flipped and it just is around backwards.
00:53:03.840 --> 00:53:17.520
And so even though the DNA part is still technically there, the instructions become disrupted badly enough that the body can't properly make a functioning factor VII, the F8, like it should.
00:53:17.840 --> 00:53:22.880
And without enough factor VII, blood doesn't clot the way it should.
00:53:23.120 --> 00:53:33.520
So people with severe uh hemophilia A may experience prolonged bleeding, easily bruising, internal bleeding into muscles and joints, chronic joint damage over time.
00:53:33.680 --> 00:53:34.000
Yeah.
00:53:34.080 --> 00:53:43.040
So I mean, obviously, if your body and and again, it's not people think, okay, if I get a scratch, like that's that's the only time it would bother me.
00:53:43.120 --> 00:53:48.000
No, like our body is caught internally like constantly forming clots that we don't even know about.
00:53:49.280 --> 00:53:49.680
Yeah.
00:53:49.920 --> 00:53:50.560
Yeah.
00:53:51.200 --> 00:53:59.200
And so again, it's just that's that's such something that could be so detrimental is just caused by a section flip flip backwards.
00:53:59.440 --> 00:54:13.440
And and scientists are interested in inversion mutations right now because for a long time they were really difficult to detect, like they knew something was wrong, but they couldn't really figure out what because they would be reading through the chain and they're like, Well, all the pieces and parts seem to be there.
00:54:13.520 --> 00:54:15.280
What the heck is is going on?
00:54:15.520 --> 00:54:26.080
And so older genetic technologies were good at spotting missing DNA or extra DNA, but inversions are a lot sneakier because that DNA is still present.
00:54:26.240 --> 00:54:32.400
So if some of the older technology, yeah, even if it was in order, the machines are like, Well, but it's all still there, guys.
00:54:32.480 --> 00:54:34.400
And they're like, Yeah, no, it's not.
00:54:34.480 --> 00:54:37.600
It's it is there, but it's all uh out of order.
00:54:37.840 --> 00:54:48.640
So, with a lot of the newer long read sequencing technologies, researchers are discovering that inversions may play a much, much bigger role in a lot of these mutations than we originally thought.
00:54:48.880 --> 00:54:59.680
And so now they're because of the newer technology and they're easier to detect, just like everything else, a lot more research has gone into it to try to figure out hey, how can we prevent and fix these things?
00:55:00.320 --> 00:55:07.360
Yeah, so mutations, the good, the bad, the ugly, some are good, some don't do anything, some are bad, and some are real bad.
00:55:07.600 --> 00:55:07.840
Yeah.
00:55:08.080 --> 00:55:14.880
Like we were saying earlier, it's kind of a I mean, just remember your body's doing this all the time and for the time, it's good to go.
00:55:15.200 --> 00:55:18.640
Yeah, which is just which is crazy in so many aspects.
00:55:18.800 --> 00:55:20.000
So, all right, guys.
00:55:20.160 --> 00:55:22.240
Well, next week we have another short episode.
00:55:22.400 --> 00:55:24.160
Until then, visit us on Patreon.
00:55:24.320 --> 00:55:25.920
I have been posting more content on there.
00:55:26.080 --> 00:55:26.960
Support us if you can.
00:55:27.040 --> 00:55:29.760
It helps keep all of this up and running.
00:55:29.840 --> 00:55:33.760
Um, because it costs monies, so any any little bit of help there.
00:55:34.000 --> 00:55:42.160
And yeah, like I said, next week it'll be another episode of uh I bet you never heard of that animal or whatever we're calling that series.
00:55:42.320 --> 00:55:42.720
Yeah.
00:55:42.880 --> 00:55:43.920
Something along those lines.
00:55:44.080 --> 00:55:44.880
You probably never heard of me.
00:55:45.200 --> 00:55:45.600
There we go.
00:55:45.680 --> 00:55:47.280
You've probably never heard of it, not betcha.
00:55:47.600 --> 00:55:49.600
All right, so until next week, guys.
00:55:49.920 --> 00:55:50.400
See ya.