Mutations, or changes in DNA sequences, are incredibly important in biology, from evolution and diversity to cancer and genetic diseases. But how do mutations happen? In this lesson, you'll learn about mutagens, which are chemicals that can cause mutations.
Mutations are changes in a DNA sequence, kind of like typos in an email. If there are just a few minor typos, you can still figure out what the email is trying to say, but if there are tons of typos, it can make the overall message impossible to understand. The same thing happens with mutations in DNA: if there are enough of them, then the protein products that are made according to that DNA sequence may be totally jumbled up and defective.
Defective, mutated proteins can end up causing various diseases, birth defects and cancer. But on the other hand, mutations are the ultimate source of genetic variation that allows organisms to evolve over time. If no mutations ever happened, there would be no diversity of life in the world, and biology would be pretty boring.
So mutations are a big deal in biology, but how do they happen anyway? Two major causes of mutations are irradiation and chemical mutagens. Irradiation is exposure to radiation and chemical mutagens are chemicals that cause changes to DNA sequences. In this lesson, we'll learn about how certain chemicals can cause mutations.
The first type of mutation we'll talk about is base analogs. You can think of base analogs as decoys; they are chemicals that are very similar to the normal nucleotides that make up DNA. In their name, 'base' refers to the nitrogenous base in the nucleotide, and 'analog' means 'analogous,' or similar to.
So what happens when a cell is exposed to a base analog mutagen? Well, first of all, let's recall what happens during DNA replication. The DNA polymerase makes a new 'daughter' strand of DNA by gradually putting in one nucleotide after the next. It knows which nucleotide sequence to make because it uses the 'parent' strand's sequence as a template.
But if the cell encounters a base analog mutagen while its DNA is replicating, there's going to be a problem. The DNA polymerase may accidentally insert one of the base analogs into the growing DNA chain instead of a real nucleotide! For example, take the base analog 5-Bromouracil (or 5BU). This molecule looks a lot like a thymine or T nucleotide, so the DNA polymerase could just put it into a new strand of DNA in place of a T. Uh oh. But the cell probably won't notice this at the time and the polymerase will just keep on chugging, replicating the rest of the DNA.
The real problem comes in the next round of DNA replication. The thing about these base analogs is that they are shape-shifters. Since 5BU looks like a T nucleotide, normally it would base pair with an A, or adenine, in the DNA, right? Well, 5BU can shape-shift, switching to a different structure that looks more like a cytosine nucleotide. What does C normally base pair with? G. So when this shape-shifting base analog is part of the recipe for making a new strand of DNA, a G could be put in instead of the A that was supposed to be there. This is called mispairing. So basically, 5-Bromouracil can cause a T-A base pair to change to a C-G base pair. The original DNA sequence has changed - a mutation has happened.
In case you're curious, another example of a base analog mutagen is 2-Aminopurine. It looks very similar to adenine, or A, but can shape-shift to look like guanine, or G. If you want, take out a piece of paper and draw yourself a picture to prove to yourself how 2-Aminopurine can cause A-T base pairs to change to G-C base pairs.
It's important to keep in mind that not all base analogs are mutagens. Some base analogs get put into a DNA strand and then, instead of changing the DNA sequence, they stop the DNA chain from growing any longer because the base analog doesn't have the right linker. It's like if you're trying to build a tower of Legos, but then you put in a piece that has a smooth top instead of the bumps that it needs to connect to the next block. This is how the base analog AZT works; it is used as a drug to slow the replication of the HIV virus that causes AIDS.
Okay, back to mutagens. The next class of mutagens we need to learn about is the base-modifying agents. These are chemicals that modify or change the structure of bases in the DNA, causing mispairing. Let's see what that means.
One example of a base-modifying agent is nitrous acid. This chemical is a deaminator; it removes amino (NH2) groups from nucleotide bases. Nitrous acid can deaminate the bases G, C and A. When it deaminates them, it basically turns them into different bases! It's kind of like if you change your hair color or get a nose job, you could look like a totally different person. You might even behave differently, to fit your new persona, right?
That's exactly what happens when nucleotides get changed by base-modifying agents. For example, a deaminated cytosine, or C, turns into a uracil, or U. You may know that Us are normally found in RNA, not DNA, and that they behave differently than Cs. Us base pair with A, or adenine. So what happens to a C-G base pair in DNA when nitrous acid is around? It can turn into a U-A base pair, which will turn into a T-A base pair after the next round of replication.
There are other base-modifying agents, too. You might not need to learn the details of these, but just to give you an idea: hydroxylamine adds hydroxyl (OH) groups to cytosine, making it look more like thymine. Again, with a piece of paper and a pencil, you can draw a picture to convince yourself that hydroxylamine causes C-G base pairs to turn into T-A base pairs.
And finally, alkylating agents like ethyl methanesulfonate (EMS), add methyl (CH3) or ethyl (CH2-CH3) groups onto bases, causing them to mispair in various ways. Whew! That's a lot of information. Let's sum up base-modifying agents by reminding ourselves that, even with all their funky names and different behaviors, they are all chemicals that modify or change the structure of bases in the DNA, causing mispairing.
The last type of mutagen that we are going to learn about today is intercalating agents, like ethidium bromide and acridine orange. These are chemicals that intercalate, or insert themselves, in between the base pairs of a DNA helix. If you look at the 3-D structure of a DNA helix, you can see that the base pairs are all stacked up like plates in your cupboard. Intercalating agents kind of squeeze themselves in between the plates. This ends up stretching the DNA molecule a bit.
And during DNA replication, as the polymerase moves along the DNA, it'll eventually come to the intercalating agent instead of a nucleotide. That's confusing. What is the polymerase going to do? Well, it's got to insert something across from the intercalating agent, so it goes ahead and puts in a random nucleotide and then keeps on moving forward. As you can see, the DNA sequence got longer by one nucleotide. This means that intercalating agents can cause insertions in DNA strands.
And not only that. Since they cause insertions of one base pair at a time, intercalating agents can cause frameshift mutations. Remember that frameshift mutations are a very serious type of mutation because they end up completely scrambling the amino acid sequence of that DNA's product.
Let's review. We've learned that one of the ways that mutations can happen is exposure to chemical mutagens, which are chemicals that cause changes to DNA sequences. We heard about three major classes of chemical mutagens.
The first is base analogs. These are chemicals that are very similar to the normal nucleotides that make up DNA. We called them 'decoy' nucleotides because they can get put into a new DNA strand in place of a normal nucleotide. But not only that - we learned that base analogs can be shape-shifters. If a base analog is put into a new DNA strand and then shape-shifts to look like a different nucleotide, we saw that the DNA sequence changes.
The second class of mutagen that we learned about is base-modifying agents. These are chemicals that modify or change the structure of bases in the DNA, causing mispairing. We compared them to people that drastically change their appearance by changing their hair color or getting a nose job. When a nucleotide's structure is changed, it will base pair incorrectly, causing mutations to happen.
Finally, we heard about intercalating agents. These chemicals intercalate, or insert themselves, in between the base pairs of a DNA helix. When the DNA polymerase encounters one of these, it doesn't know what to do, so it puts in a random nucleotide. This can end up causing insertions and frameshift mutations in the DNA.
By exploring this lesson, you could subsequently be prepared to:
- Give the meaning of mutation and discuss its possible effects
- Highlight two main causes of mutations
- Express detailed knowledge of the three classes of mutagens