 Hey everybody, Dr. O here. So we've talked about replication of DNA, now I want to talk about mutation. So if everything works perfectly then our DNA would be replicated, transcribed and translated with no problems whatsoever. But we know that's not true because mutations occur. So first of all, what is a mutation? It is a change in the sequence of DNA. When you hear the word mutation or mutant you think bad, but not all mutations are bad. Without mutation there wouldn't be alleles, there wouldn't be different versions of genes which means there wouldn't be any evolution. So an example of a good mutation would be for someone like me, I like cheese, would be the lactase persistence mutation. So at some point, not that long ago, till about 10,000 years ago in Northern Europe and 7,000 years ago in Africa, all humans were basically lactose intolerant. But this mutation led to the persistence of the enzyme lactase after humans were weaned from their mother's breast so we could still consume dairy products. I think that's a very good mutation. So mutations can be beneficial if they increase your chances of surviving and reproducing. They can be lethal if they decrease it or they can be neutral, right? Having some hair on your knuckles, freer, fixed ear lobes, those things shouldn't play a big impact in your chances of survival. So before we talk about the types of mutations, how many do we have? Depending on the cell and different mutation rates, there's estimates that between 10,000 and 1 million mutations occur per cell per day. So huge, huge numbers. Thankfully, the huge majority of those are going to be repaired. We have DNA repair mechanisms that work all the time. But we do still accumulate some mutations, right? Mutations are caused by just our normal metabolism, like free radicals, reactive oxygen species. Regular just copying errors are going to occur. UV radiation, gamma rays, x-rays, chemical mutagens, mutagens or anything that increase mutation rates, viruses. So mutations come from all over the place. But thankfully, we do get a lot of mutations. But thankfully, most are repaired. So you might think about things like cancer and how maybe 40% of us are going to get cancer at some point. You think that's a big number. But if you look at the number of mutations that occur per cell per day, shouldn't be a wonder that 40% of us get cancer. Sadly, it should be a wonder that we don't all, in a sense. So mutations, most mutations are bad. And I won't go into a huge detail here, but most mutations are bad, right? Think about it. You're perfect already, right? We're the evolutionary winners, right? We are here because we are good. We've got good combinations of genes. So we're the survivors, right? So if you're going to change something, chances are it's going to be worse. So here's the example I like to use. Take your favorite book. Your favorite book probably has a typo in it. It probably has the word the twice in a row or something like that. A positive, if you just open the book, close your eyes and randomly point to a word and you change that word, chances are you're going to make that book worse because the book was almost perfect. But you might hit that second and get rid of it or you might change that typo, right? So there's a very small chance you made that book better by changing something in it. But it's way more likely that you made it worse because it was already pretty good, right? Such as kind of what a mutation is and where they might come from and just some little bit of conversation about why most of them are bad but not all are bad. Let's look at the different types of mutation. Let's go a little closer here. So first we have what are called point mutations. The other name for these are base substitutions. The key thing I want you to remember here is that one base is replaced with another, that's why it's called a base substitution. And I also want you to note this is by far the most common type of mutation, where one base is just accidentally replaced with another one. So you see there are going to be different types of them here though. We have silent mutations where there was a base substitution but it didn't impact which amino acid was laid down so it's going to be silent. No effect and I'll show you why that is in just a moment. How could you have a mutation but it not change anything? It has to do with the term called degeneracy but I'll show you that with genetic code and I remember to use valine as the example. Missense mutations are going to be where you have one base substitution that changes one codon which does change one amino acid. So that's called a missense mutation. That's the most common type that we talk about of point mutations or base substitutions. Then we have a nonsense mutation. These are going to be worse where you have a mutation that changes the codon but it changes it instead of one that lays down another protein in a chain or amino acid in a chain sorry. It changes it to a stop codon or a nonsense codon and stops the protein from being produced so that can be pretty disastrous. But generally speaking point mutations or base substitutions think most common type of mutation but generally speaking less damaging, least deadly. Here we have a frame shift mutation. This is going to be where you add or remove base pairs or like it says there, insert or delete base pairs. The reason this is called a frame shift mutation is remember, your RNA is read three letters at a time. So if you add a base pair or take a base pair away, you don't just affect where that occurred. You affect the reading frame. So you'll see there that you added a couple or the TNA were removed. So now instead of being, so we both sides here have AGC. But instead of being GTA, it's now GCC. Everything's moved over to base pairs. So that one screwed up but so was the next one. The next one was supposed to be CCC and now it's CTA. That's why it's called a frame shift mutation. You change the reading frame. So back to our book example, whereas a base substitution would just change a letter in one word. A frame shift mutation, imagine your favorite book and on page 120. From there on out, every word is the end of the last word and the beginning of the next word. The entire rest of the book would be jumbled up. That's why frame shift mutations are way more likely to cause serious harm. Before we're done, I do want to review that term degeneracy. And I said I would use valine. So we got to find that down there. All right. So degeneracies degenerate. To say that your code is degenerate sounds terrible, but it's not. What that means is you can actually handle some amount of mutation if you get lucky and a mutation happens in the right spot without it causing any problems. So it was called a silent mutation. So you see down here in the lower left hand corner, the codons GUU, GUC, GUA and GUG, all code for valine. So if you add a point substitution or a base substitution or a point mutation that turned GUU into GUC, it wouldn't cause any problems. Because you'd still put valine in the right spot in that protein. That's why it's a silent mutation. If it's a missense mutation, now if you turned GUU into GCU, now you have a problem. Because there's supposed to be a valine put there in that protein chain. Now you're going to put an alanine there instead. So that's going to be a regular missense mutation. A nonsense mutation, let's take that UAC up there. If that's mutated into UAA, you went from instead of laying down a tyrosine in the protein chain, you have a stop sign. So that amino acid's wrong, but you won't build any more moving forward. That's called a nonsense mutation. Okay, so that's what mutations are. That's the different types of mutations. I hope this helps. Have a wonderful day. Be blessed.