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Lecture 6

Lecture 6- Mutation


Human Biology
Course Code
Michelle French

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Thursday, January 22, 2009
- Todays lecture is now moving into a second part of the course which is talking
about mutation and today the mutations will be relatively small and in the next two
lectures following, she will talk about how to correct mutation and the following
ones will be one chromosomal abnormalities so larger changes.
- So today’s lecture is starting about mutation and it will be about smaller ones.
- Recall that when you look at DNA and you look at its properties, there are 4 key
properties that are important when you study genetics: the idea that you can store
information, it can be replicated or copied, the information can be expressed and
that kind of ideas and topics are what she’s been talking about already especially
expression. But DNA can also change and that can be useful because that change
can help to drive differences amongst a species and also to drive evolution.
- The different types of mutations are listed and the concept is that while we think
of mutation as a bad thing, it can also be useful b/c it provides variability which
can then be taken up & used during evolution so there are some good & bad things
about mutation.
- Shown here are various types of mutations but for clarity, she has these shown on
the next slides.
- We study mutations a lot, she even talked about mutations in the course already
without defining it in great detail b/c what mutations allow us to do is to identify
genes. Mutations can be markers for certain kinds of genes.
- We saw that in the last time when she was talking about development, that
mutations were created & we could subsequently identify certain genes involved in
incorrect embryo development. That was a way to mark the genes, by mutating
them we could see what would happen if something went wrong & therefore, we
could study the gene itself.
- Mutations can also disrupt the gene function which helps us understand how the
normal or the wild type gene works When we see that a function has gone missing
b/c we have mutated the gene, it gives us some sense of what that gene actually
- Wild type is the form that is mostly found in nature or if youre looking at a
laboratory stock of animals or plants, the standard laboratory stock it is the
common gene variant you have, it is the wild type & it functions normally.
- A mutant is a form that has changed due mutation also known as a change due to
alteration in the sequence of the DNA. It varies from the wild type.
- In a forward mutation you go from the wild type to the mutant version so that is
called the forward mutation. Reminder that each allele or variant of the gene is
represented by a letter, sometimes the wild type also has a plus indicating that it is
the wild type & in this example, we go from A+ to smaller a or you can go from a
small d+ to a big D. The upper case means that it is dominant & the lower case
means that it is recessive.
- In some instances, having had these mutations happen, it is sometimes possible
for the mutation to reverse back to the wild type & that is called a reverse mutation.
What happens in this case is that the novel mutation reverts back to the wild type &

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another name for that is called reversion so you go from the mutant to the wild type
as is the case shown here. That happens rarely, not nearly as frequently as in a
forward mutation, but it does happen, you could go back to a wild type version.
- Recall for the DNA structure, we have the double helix & the hydrogen bonding
of the different bases.
- There are two classes of bases, the purines which are shown here with A & G
which have a two ringed structure & the pyrimidines which are the DNA C & T
which have a one ring structure. C & T are pyrimidines & A & G are purines.
- Here is a catalogue of the kinds of mutations that can arise in DNA & there are
certain names for these & you have to understand what these names are.
- One idea would be that you have a substitution in the nucleotide & that is called
the base substitution & there are special names depending on what base gets
changed. When you talk about a transition, what happens in a transition is that one
type of purine is converted to another type of purine, in other words where an A
turns into a G or a G turns in to an A. Or in another type of transition, a pyrimidine
converted so one type of pyrimidine is converted to another type of pyrimidine so
C & T can be converted. Transitions are sticking with that group, purine to purine
or pyrimidine to pyrimidine. Behind shows us the base pairing, the A & T on the
two strands & the A & T would be converted to a base pairing of G & C because if
A is converted to G, then the G will pair with C that will happen.
- That is called a transition, another type of substitution is called a transversion &
in that case, a purine becomes a pyrimidine or a pyrimidine becomes a purine. Here
the idea can be an A to a C, or T to G. You have to know the difference between a
transition & a transversion & what the consequences are.
- As well there can be insertions or deletions, these can be really small or these can
be really large, these can be deleting one nucleotide base pair or they could be
inserting one pair. So these are one or more nucleotide pairs that are either added
or deleted from the sequence. When you’re talking about these mutations as a
group, they are called indel mutations, which is indel kind of contraction of
insertion or deletion.
- As well there is something called an inversion, in that case imagine you have a
segment of DNA that gets chopped out in two places, & it gets flips 180 degrees &
joins up, that will change the sequence & that is called an inversion.
- Another type is called a reciprocal translocation where two parts of the
chromosome will switch places, so a chunk of chromosome 1 goes into
chromosome 8 & a part of chromosome 8 goes into chromosome 1. That is usually
a much larger change.
- For todays lecture, we will focus more on small insertion or deletion & base
- Here we have made a list of quite a few of the different types of mutations, so
how do they arise? How do we get those?
- In some cases these happen totally spontaneously, in the total absence of a
mutagen, a mutagen is something that causes your DNA to be mutated, we
probably know about them, there are different substances that do that. For example,
chemicals in cigarette smoke are known mutagens or other types of chemicals are
known as mutagens. Even UV light is a mutagen but some mutations just arise
spontaneously. They provide a kind of background rate of the mutations that we
have in our DNA, the background rate is around two to twelve *10-6 mutations per
gene per gamete.

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- Mutations can also be induced by geneticists so you get the action of a mutagen
which alters the sequence.
- In our textbook, they talk a lot about the different types of mutagens we wont
talk about them in lecture but we must know them like ethidium bromide & etc,
etc. Know them but she won’t go through a list of them right now, she wishes to
focus on spontaneous mutations.
- One type of spontaneous mutation is depurination where here is the DNA with
the guanine, & the purine (remember guanine is purine) gets removed & it
becomes an apurinic site so the guanine is released so that is one type of
spontaneous DNA mutation.
- Another type is deamination where the amino group of cytosine gets converted to
uracil, the consequences of that are shown in the figure. For example if cytosine is
normally paired with guanine, with deamination that happens without repair,
during replication these strands will separate & the U will pair with A which is
what it normally pairs with. Imagine these strands are duplicated & if we use the U
as a template, the other strand becomes an A & then in the 2nd round of replication,
the U will be replaced with a T b/c this will be a newly synthesized strand in this
particular cell & this would be the parental strand within a newly synthesized
strand. You can see that relatively quickly in a couple of generations, you go from
a CG pair to an AT pair & that is if you have no repair mechanisms.
- X rays are another thing that causes mutations & that is why when you go to the
dentist’s office, they cover you up as much as possible with a lead apron to prevent
you from being exposed to X rays. What X rays do is chop the double stranded
DNA & then the DNA re-anneals so you can end up with deletions.
- As well, UV light shining on our skin from sunlight can hit the DNA & cause
thymine dimmers & you can see the structure of these in the slide. That would be
another type of spontaneous mutation.
- Lastly, you can also have oxidation of guanine getting that weird structure in the
slide & this unusual base ends up pairing not with C as it should if it were really
truly guanine, it ends up pairing with A. If you check on the right hand side, you
see that G & C normally pair but if there is oxidative damage, then in a round of
replication you will get A coming in on the daughter strand that is synthesized &
second round of replication will give you a mutant sequence with T & A.
- This is how you can introduce mutations into the genome & these would be
happening all the time in us.
- That would be for the kind of substitution changes, what about these indel
mutations? These indel mutations arise when there is slippage of DNA during
- On the left you see how you can get an addition of info, in other words an
insertion, & on the right you can see how you can get a deletion & both of these are
happening during DNA synthesis.
- Here is our parental strand in blue, the newly synthesized strand in yellow. If
there is a lot of Ts especially in a repetitive sequence, then the newly synthesized
strand can slip & notice this base is popping out, it isn’t participating in base
pairing so it has a loop there & it gets stabilized b/c of these repetitive sequences so
that when the copying happens, it is almost as if you’re copying a 2nd T you
shouldn’t have had before. Therefore in this strand, when it becomes a template
you’ve introduced a single insertion right into that sequence, allowing an insertion
to happen in the sequence.
- You can see a similar type of idea happening to cause a deletion. For example,
this is a parental strand in blue & this time it is the parental strand that is looping
out, that nucleotide there loops out & the newly synthesized strand is base pairing.
In this case in the newly synthesized strand, you’re now missing the bases that
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