The causes of genetic mutations

Voiceover: So, today we're going to talk about the causes of genetic mutations, but first let's just do a quick review of the idea that mutations are mistakes in a cell's DNA, and there are two main types of mutations that we see when we look at a cell's DNA, and the first is called point mutations, and that's when one DNA base is switched out for another, which usually results in a change to one codon in the RNA sequence. Frame-shift mutations are when the reading frame of the RNA is altered, and while the actual nucleotides in the RNA sequence haven't changed that much, the reading frame of the RNA strand has shifted, meaning that many different RNA codons will change as a result, and we're going to take a look into what causes these point and frame-shift mutations. So, point mutations are caused by base substitution, which is when one DNA base is substituted for another, and there are a couple of different types of base substitution. A transition is when you have a substitution of adenine for guanine or vice versa, which is a swap between two purines, or a substitution of cytosine for thymine or also vice versa, which is a swap between two pyrimidines. A transversion is when either adenine or guanine is swapped for either cytosine or thymine, and in this type of base substitution, you have either a purine being replaced with a pyrimidine or a pyrimidine being replaced with a purine. Now, the last kind of mutation that can lead to a point mutation is a mispairing, which some people call mismatching, and that's when a DNA strand has a non-Watson-Crick base pairing. Normally, A pairs with T and G pairs with C, but when you have a mispairing, that's when A and C pair up or when G and T pair up, and it's much more common for mispairings to occur between a purine and pyrimidine, as opposed to between two purines, like A and G pairing up, or two pyrimidines like C and T pairing up. Next, we're going to talk about frame-shift mutations. So, let's say that we have this DNA strand here, with three repeating CTC units and an extra C on the end. This would then be transcribed into an RNA strand with repeating GAG units and an extra G on the end, and our three codons would be the three GAG units, which would then each translate to a glutamate amino acid. Now, one way you can cause a frame-shift mutation is through an insertion, and that's when an extra DNA base finds its way into our sequence. So, here we have this extra cytosine base, that I've underlined, falling into our sequence, and this additional C base would lead to an extra G being thrown into our RNA sequence, which would then shift the codon reading frame of our RNA strands during translation. So now, instead of three GAG codons, we have just one GAG codon and two GGA codons, with two extra bases on the end. This would then code for one glutamate residue and two glycine residues, instead of three glutamates. The other way that you can cause a frame-shift mutation is through a base deletion. So, in a deletion, we drop off one of our bases from our original sequence. So, here I've dropped that first thymine base, and this would also result in a shift of the RNA reading frame. Now, instead of having three GAG codons, we have a GGG codon and two AGG codons, which would lead to a protein with a glycine and two arginine amino acids. So, overall, insertions and deletions can both lead to frame-shift mutations. Now, we can also talk about large-scale mutations, which instead of being at the level of individual nucleotides, are usually seen at the chromosomal level and can affect many genes, instead of just a few base pairs. So, first we'll talk about translocation, which is when a gene from one chromosome is swapped for another gene on a different chromosome. Now, it's important to see that translocation refers to gene swapping between nonhomologous chromosomes, which means that if this blue chromosome were chromosome 10, then the green one could be any chromosome aside from chromosome 10, and this is what sets translocation apart from the process of crossing over that occurs during meiosis between homologous chromosomes. The next large-scale mutation we'll talk about is chromosomal inversion, and that's when two genes on the same chromosome switch places. So, here our green and blue genes are being swapped and end up on different parts of the chromosome after the mutation. Now, since both of these mutations don't always affect the individual nucleotides coding for a gene, it's important to see that many of these types of mutations affect how a gene's expression is regulated, in addition to changing what the genes actually code for. Remember that the position of a gene on a chromosome partly determines how it's regulated, and this could be due to histone configuration, promoter regions, or any other regulatory process. So, what did we learn? Well, first we learned that small-scale mutations affect the DNA at the nucleotide level, and of these small-scale mutations, we have point mutations, which can be caused by transitions, transversions, and mispairings, and we also have frame-shift mutations, which can be caused by insertions or deletions. Next, we talked about large-scale mutations, which affect the DNA at the chromosomal level, and the two large-scale mutations we talked about were translocation and inversion.