Short Stuff: Genetic Mutations

All sorts of exotic and often terrible stuff runs through our heads when we think of genetic mutations, but the vast majority of them are caught before they happen thanks to the crack teams replicating our DNA in our cells. See omnystudio.com/listener https://omnystudio.com/listener for privacy information.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Speaker 00

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• 0:04Josh Clark?

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• 0:39Josh Clark?

  Hey, welcome to the short stuff. I'm Josh and there's Chuck and this is short stuff. The mysteries of genetic mutations edition.

• 0:48Speaker 02

  That's right, because we're gonna talk about the X-Men.

• 0:53Josh Clark?

  Yeah, a mutation. I mean, I don't know if it would help you join X-Men, but there are mutations that alter people, sometimes in positive ways. We usually associate it with negative stuff like a congenital disease or something. A lot of them are neutral. I think actually the vast majority are neutral. They don't really have any noticeable effect. Some are beneficial. Lactose intolerance, immunity to malaria, when someone's vestigial tail turns into a glorious full tail. Those are all beneficial genetic mutations, but all of them share something in common. And that is that the replication of the person's genome had some sort of error while it was being copied.

• 1:39Speaker 02

  Is lactose intolerance a beneficial?

• 1:41Josh Clark?

  No, lactose tolerance.

• 1:43Speaker 02

  I think you, I thought you said intolerance.

• 1:45Josh Clark?

  Oh, I'm sorry. Yeah, so lactose intolerance is apparently the, the, the baseline, the default. Lactose tolerance is from a genetic mutation.

• 1:55Speaker 02

  All right, well, let's get into this. Let's talk about DNA or deoxyribonucleic acid, as we all like to call it.

• 2:03Josh Clark?

  Such a great word.

• 2:04Speaker 02

  Around the campfire. That's a molecule that's gonna carry genetic material, I almost said mutation, when you're developing as a, as a. Future human. And structurally, I think we've all seen the, if you've seen Jurassic Park, you've seen what these double, this double helix looks like. It's a long molecule comprised of nucleotides. And there've been, you know, there's two strands to that coil that form the double helix that kind of wind around each other. And that's, that's what the DNA, the full DNA, what would you call it? Just molecule looks like?

• 2:42Josh Clark?

  The genome? Yeah, the molecule, DNA is a molecule.

• 2:45Speaker 02

  Yeah.

• 2:46Josh Clark?

  And you said it, man. It is long. Apparently, if you stretched it out, it would be about two meters or six feet tall.

• 2:52Speaker 02

  Yeah.

• 2:53Josh Clark?

  If you could figure out how to stretch it out. It's amazing. And it's made of 3.1 billion base pairs of nucleotides. Thymine, cytosine, guanine, and adenine. And adenine goes with thymine and cytosine goes with guanine. And you put all that together, just with those combinations, you have a galaxy of different code that's embedded into the DNA that serves as how, like, it tells the rest of your body, each cell, what it's supposed to do and how to do it. And usually, that has to do with expressing proteins.

• 3:32Speaker 02

  Yeah. And, you know, like you mentioned, as the cells divide and the DNA is making copies of itself, there might be errors here and there. And that's where those mutations come from. In the egg, if they're in the egg and sperm cells, those are going to be passed on to the next generation. So that's a genetic mutation that's going to carry on and cause disease or genetic disorders. You can also have what's called a somatic mutation, and that only affects you. It's not inherited by your future kids.

• 4:02Josh Clark?

  Right, exactly. So really, the big problem is genes, like a gene not being replicated correctly. And a gene is just a stretch of nucleotide base pairs along your genome that's, that together shows how to encode a protein. It's the instructions to how to do a specific Thing. And again, it's just a segment along your, your DNA. And when that stuff gets copied, if there's any kind of error, like say you match up an adenine to a cytosine, it's going to prevent that, that cellular process, that, that whatever the gene is telling the cell to do, to not be able to be performed correctly. Hence a mutation.

• 4:47Speaker 02

  Yeah. And our cells are constantly copying themselves, either replacing old cells or damaged cells. And when that happens, when they're doing that copy, that double stranded DNA is going to split into the two parts and each strand is copied on its own and then they come back together. And when that happens, there can be errors. The good news is it's approximately one in every 100 million replications this happens. So that's a, you know, that's a pretty good statistic to have in your hip pocket. The other good news is DNA knows what it's doing. So it generally knows when an error happens and they try to and often can repair and correct that before any problems arise.

• 5:29Josh Clark?

  Yes. I think that's a pretty good place to take a break, Chuck. So let's take a break, Chuck.

• 5:34Speaker 02

  Let's do it.

• 5:49Josh Clark?

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• 6:42Josh Clark?

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• 8:04Josh Clark?

  Okay, so there's basically two ways that you can, that a genetic mutation can develop the cell replication, which we've talked a lot about, and then environmental influences. And there's actually different ways it can happen even during cell replication. There's totomeric shifts, which is where the nucleotide itself undergoes a quick chemical reaction to where suddenly adenine turns into, I don't know, silver, just for a second. And then it eventually turns back. But if that adenine nucleotide is being copied at that moment, you're going to have a silver nucleotide in your DNA. And silver just don't work when it comes to making proteins.

• 8:47Speaker 02

  Yeah, so that's sort of due to bad timing. Another thing that can happen as far as those errors go is, it's called mispairing. And was this a How Stuff Works article?

• 8:57Josh Clark?

  Yes, it was.

• 8:58Speaker 02

  Yeah, they did a pretty good job of putting this in terms we could understand. If you imagine those two DNA strands that work together or zip together like a zipper. Sometimes that zipper doesn't align.

• 9:09Josh Clark?

  Your penis gets stuck in it?

• 9:11Speaker 02

  Oh my god. And that that can happen when the DNA is getting zipped back up. And that can cause part of parts of it to be skipped over, or maybe something added that shouldn't be.

• 9:21Josh Clark?

  Right. And then the third way that a mutation can happen during replication is what's called jumping genes. Cousins of jumping jacks. And that is where, so these genes are normally, I don't understand this fully, but genes, which again are just stretches of code on your DNA, can actually move. They can change positions. They can change places. Sometimes they replicate themselves and and the the replicant goes and embeds itself in another segment of your DNA. And if it does so in a gene, another gene, then it's going to mess up that gene's ability to to perform its function. Did not know that that was a thing.

• 10:00Speaker 02

  Did not either. Had never heard of jumping genes. I've heard of jumping beans and jumping jacks, but never jumping genes.

• 10:07Josh Clark?

  Very nice.

• 10:08Speaker 02

  So that's the the ways that can happen as far as like an error occurring in your body.

• 10:15Josh Clark?

  Right.

• 10:15Speaker 02

  On a cellular level. You mentioned external factors. One of the big ones, and I didn't know to this extent even, is is radiation. And you might be thinking like, yeah, so you just don't get x-rayed when you're pregnant, like that solves everything, right? That's not necessarily the case, because UV radiation can be a very big cause of mutations, specifically when it's called like a sunburn on your DNA. If you're have too much UV radiation, you can they can form something called, how would you say that?

• 10:51Josh Clark?

  I'm going to say perimidine dimers.

• 10:54Speaker 02

  Perimidine dimers?

• 10:55Josh Clark?

  And I looked, I was like, is that a misprint? Is it supposed to be dimmers? And nope.

• 11:00Speaker 02

  No, it's dimers. And especially thymine dimers that can distort that DNA structure. And that's sort of like a sunburn on the DNA. And that happens when a couple of DNA building blocks are stuck together. And that's oftentimes caused from, you know, sun exposure.

• 11:18Josh Clark?

  Yeah. There's also chemical factors too, which are basically biological or environmental factors. Essentially, what it is, is there's different kinds of chemicals that can make their way into the DNA in the nucleus of a cell and just mess with it. Sometimes they mimic nucleotides and they get pulled in, like, like just some guy walking down the street, getting pulled into the Jimmy Fallon Late Night Show because they couldn't get enough people to fill seats. That can happen during DNA reproduction, replication. And when that, that nucleotide that didn't mean to be there gets entered into the, the new code of DNA, it, again, problems arise. That's a mutation.

• 12:03Speaker 02

  The problems arise when they have to sit there and watch Jimmy Fallon.

• 12:06Josh Clark?

  That's right.

• 12:07Speaker 02

  Oh, man.

• 12:08Josh Clark?

  Oh, boy.

• 12:09Speaker 02

  I'm gonna hear it. There are also biological factors, like a virus can cause, that can get in the DNA.

• 12:17Josh Clark?

  Yeah.

• 12:18Speaker 02

  And that can lead to mutations. And then there's some other environmental stuff as well, right?

• 12:22Josh Clark?

  Yeah. De-animating agents, they actually remove parts of our DNA. Substances, like stuff found in cigarette smoke, can stick to DNA, like so much tar, and change the shape of the DNA. Essentially, you don't want anything going anywhere near your DNA. And if there's something that happens, and it happens on an important gene, that mutation's going to produce some sort of problems down the line. But our body is actually really, really good at either preventing these errors or correcting them when it finds them, which is just mind-boggling to me.

• 12:59Speaker 02

  Yeah. It, it's super cool that our body can do this. Sometimes it's like, it's called a direct fix. And these are, these are just small, little errors, like they likened it to a road crack. And they also likened it to just a quick patch on that road. The cell just directly fixes it. Super quick, like.

• 13:16Josh Clark?

  Yeah. And we should say, the cell, the, the, yeah, the cell that's transcribing the DNA is aware of it because there are different, different molecules that proofread.

• 13:28Josh Clark?

  The newly created DNA to make sure it matches the original.

• 13:33Speaker 02

  Amazing.

• 13:33Josh Clark?

  Yeah, it is. So if they find a mismatch, if they find just some stretch, it could be big, small, whatever, they'll actually cut it out, excision, they'll digest it, and then they'll reproduce the correct version of it and then connect it to that part that they cut out of the DNA and then zip it together.

• 13:54Speaker 02

  And if it's, if a whole section of DNA gets damaged, they can go to another DNA strand and say, hey, I'm glad you're here because we're going to use you now to come fix this other strand.

• 14:06Josh Clark?

  Yeah. Thank God you're here. They were about to pull us into Jimmy Fallon and we needed something to do.

• 14:12Speaker 02

  That's a oft said thing in my house. Thank God I was here because I know we mentioned War of the Roses, the movie, How It Holds Up. That's one of the great lines from War of the Roses when they are separated, but Michael Douglas is still in the house and the Christmas tree catches fire and he runs downstairs and puts it out and screams, "Thank God I was here." And I say that a lot and it's just whenever anything dumb happens that I saw for the family, I go, "Thank God I was here."

• 14:39Josh Clark?

  That's great. That's a great thing. Man, Chuck, everybody loves Chuck for reasons like that.

• 14:45Speaker 02

  Not everybody, just like Raymond.

• 14:47Josh Clark?

  All those people can go soak their heads.

• 14:49Speaker 02

  Oh, okay. Thank you.

• 14:51Josh Clark?

  Well, since I think we're out of stuff to talk about, short stuff is out.

• 15:00Speaker 03

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