Today is to learn about the mechanisms that allowed bacteria to move from that original common ancestor that showed up on planet Earth three and a half billion years ago to being the most diverse domain of all of the three domains of living things. And there are two major categories of changes that occur that we want to talk about today. So one are mutations. This is where there is genetic change that then gets passed from parent cell to daughter cell.
And then there's another process called lateral gene transfer, also called horizontal gene transfer, and this is where organisms actually share DNA in the same generation. A quick reminder about mutations. So mutations can be neutral or silent. This is the large number of mutations that occur that have this characteristic.
Maybe there's no change in the protein sequence, or maybe the change doesn't have a big effect on the protein. Maybe you change, for example, a hydrophobic amino acid for another hydrophobic amino acid, and it doesn't result in a problem with the protein folding. Mutations are also commonly detrimental. So this occurs when a key amino acid is changed, and this causes the protein to not function, or maybe the protein is truncated, so it stops too soon, the amino acids stop.
being added to the growing polypeptide chain too soon so the protein doesn't finish, for example. And sometimes we're thinking about mutations that occur outside genes but affect the regulations of genes and cells. And then we've said all along that those really magical mutations that actually result in a more well-adapted organism are very rare, but certainly they explain why traits get selected for.
If you end up with an advantage, that's going to allow you to have a better chance to survive and reproduce. All right, so mutations are permanent changes in DNA sequence, and they can be spontaneous. So oftentimes, changes occur as DNA is being copied.
So if you watch the Amoeba Sisters video, you saw them describe how frequent spontaneous generations are and how the cell really has built-in mechanisms for proofreading and correcting those mistakes. Changes in DNA can also be caused by chemicals called mutagens. They can be caused by exposure to ultraviolet light and also caused, usually major damage, is caused by something called ionizing radiation. Spontaneous mutations have an error rate of about one in ten thousand, but again bacteria and all cells are so good at fixing those mutations as they're being as the DNA is being synthesized, they actually only persist in about one to every ten to the nine bases.
And that's really good because you don't want to have a lot of these changes. We know that most of them are going to be neutral or detrimental. So that's a very very low spontaneous mutation rate, but in a bacterial population where you have ten to the seven cells, which is not uncommon, there's going to be a few mutants in every generation.
And so this the effect of spontaneous mutations is an important source of genetic variability. And if you think about this from a survival of the fittest kind of point of view, it doesn't really matter if a few bacteria become less fit and die off, as long as overall you're occasionally allowing your organisms to become more fit and better adapted to the environment. So in some ways, you know, the way evolution works is you sacrifice many to support a few. that then have an advantage and can go and take over a new niche or a new ecosystem. When we think about DNA mutations on the DNA level, we can actually use words as a great example of the types of mutations that are there.
So if this is the normal word, beast, if you do something called a substitution, where you substitute an F for the B, it now is a new word, it's now feast. how I want you to think about changes in DNA, that when you make a change in DNA, you're going to create new proteins. The new amino acids are going to be added in many cases. What about an insertion? So this is also called a frame shift mutation.
We'll talk more about those in a moment. But if we add an R in between the B and the E, the word now changes to breast. And of course, feast and breast have totally different meanings than beast. Sometimes Bases are deleted, so if you delete the A in this case, you get best.
These two actually are major problems for cells, these kinds of insertions and deletions, because they result in a reading frame shift. And then there's inversion, so here we're actually switching a T for an S. So these are all common kinds of mutations that cells see when they are either dividing or they may be exposed to a mutagen.
So point mutations, so these are the kinds of mutations, if you would go back to the last slide, we tend to think of these as substitutions. So point mutations can have different effects. So you can have this is the this is the normal DNA here you can have a silent mutation so here where you're changing the c to a t but it doesn't change the amino acid that gets added so both ttc and ttt encode lysine so even though a mutation happens it's basically silent the cell is not completely unaffected by the change sometimes there are mutations called nonsense mutations This is where if we switch the T here to an A, now we actually result in no amino acid being added. It turns it into a stop codon. So this is going to result in the protein being shortened.
And oftentimes this means the functional group is gone, so it no longer can perform the work that it needed to do. And then there are mutations that occur that we call missense mutations. So...
In the case of lysine and arginine, these are two very similar amino acids. They both have positive charges. If you replace, in this case, the T in the middle with a C, you end up encoding arginine. And oftentimes, because those two amino acids are so similar, the protein will still fold correctly and it won't cause a big problem for the cell. Now, if there's a non-conservative mutation, so in this case, Instead of adding a C, we're going to have a G at the DNA.
This is going to result in the amino acid threonine. Threonine is uncharged, and it's actually just a polar amino acid. This is going to result in a major change to the protein, and potentially it's going to disrupt the way that protein folds.
If it's an enzyme, maybe that protein will no longer be able to perform its function. So those are different kinds of point mutations, single mutations that occur at the DNA level. I said frame shift mutations were bad news.
So what happens in a frame shift mutation? Well, in a frame shift mutation, so here's our original sequence, and then let's just focus on this T here. If you just switch out the T for a C, oftentimes this will change one amino acid or have no effect. But if you, instead of switching out the T, if you actually add a C in the middle, so now we've added a base.
What this does is it actually changes the reading frame for the entire, the rest of the sequence. So here's an example here that may be a little bit easier to see. Here we have a deletion. So here we had U, U, U, and that encoded phenylalanine. But if the U gets lost, right, then what happens is everything shifts this direction.
Now U, U, G encodes leucine. And instead of having, instead of having. phenylalanine, glycine, isoleucine.
We have leucine and then we have an alanine. So we have a GCA instead of UUU, GGC, and then AUA, right? The GCA is now in reading frame where it wasn't before.
This almost always ruins the protein. Usually you end up truncating it because you hit stop codons that weren't there originally. you often end up adding a few of the incorrect amino acids. And this happens whether or not you delete a base, the way we showed here, or if you add one in the middle, you're still going to shift the reading frame. In order for this protein to be made correctly, this needs to be a codon, this needs to be a codon, this needs to be a codon.
As soon as you pull one of these bases out, you're shifting everything forward. Every codon after this point is going to be incorrect. It's going to not be the original codon that the bacteria needed to make their proteins.
So these are frameshift mutations, and usually they're really a problem for cells. Mutations are passed along. This is the thing about them.
If you have a mistake made in making an RNA, or let's say a ribosome makes a mistake in building a protein, that's just one mistake, and the next time the DNA is transcribed to make RNA or translated, those mistakes will be gone. But when you have a mistake in DNA, Because DNA gets copied and goes from parent cells to daughter cells, those mutations will be passed on for the lifetime of the cell. So here's our normal parent DNA and you can see we have a mutation on one side. This is caused by an acid and the parent DNA on this strand as it gets copied you can see that that error gets copied and all of the rest of the daughter cells that are made from this cell are going to be altered for the rest of the lifetime of that cell. Now as you get older what happens?
Well more and more mistakes accumulate in your cells and We know that this is one of the reasons why we think of cancer as a disease of aging, because the more mistakes that accumulate in cells, the more likely you are to mess up enough of the control mechanisms that cells have to prevent uncontrolled growth, so that they eventually, those cells get messed up enough that the cell can no longer control growth, and it's going to divide without regulation and become a cancer cell. So this accumulation of Mutations is something that happens in our cells over our lifetime. Now what happens if this change here occurs in sperm and egg?
Well then this change could result in a in a altered sperm or an altered egg and those mutations would get passed along to your to your offspring. And actually we know that this is really common. We call these de novo mutations and if we sequence your mom and dad and then we sequence your DNA we would find all sorts of spots in your DNA where these changes had occurred.
Now the thing is that you have four billion letters and a few of those don't usually make a difference. But once in a while we think that for example autism might be the result of these de novo mutations. And the parents don't have a problem but the child does and it seems to be just a mistake that was made at some point making those sperm and egg. And they result in this phenotype, this autism phenotype that the children have that the parents don't share.
All right, so that's a little bit on mutations and the kinds of mutations. And the next thing we're going to talk about are the causes of mutations, the causes of DNA damage, and examples of how DNA is repaired.