Gene MutationsGene Mutations

Changes to the Changes to the nucleotide nucleotide sequence of the sequence of the genetic material of genetic material of an organism. an organism.

Dr. TimmelDr. Timmel

MutationsMutations

Mutations arise when the sequence Mutations arise when the sequence of nucleotides within an organisms of nucleotides within an organisms nucleic acids is changed.nucleic acids is changed.

The impact of these mutations on The impact of these mutations on the organism can range from life the organism can range from life threatening to completely threatening to completely inconsequential.inconsequential.

Mutations are random, though some Mutations are random, though some risky behaviors can put an individual risky behaviors can put an individual at a greater danger of a mutation.at a greater danger of a mutation.

The good, the bad and The good, the bad and the ugly.the ugly.

Mutations are an important Mutations are an important ingredient to the theory of ingredient to the theory of evolution by natural evolution by natural selection, as they increase selection, as they increase the amount of genetic the amount of genetic diversity in a population.diversity in a population.

Usually (>99%) mutations Usually (>99%) mutations are deleterious (bad) to an are deleterious (bad) to an organism.organism.

However, on occasion, a However, on occasion, a mutation gives an individual a mutation gives an individual a selective advantage, and will selective advantage, and will increase in frequency within increase in frequency within a population.a population.

Mutations will never, ever Mutations will never, ever give you superpowers.give you superpowers.

What causes mutations?What causes mutations?

Agents that can Agents that can cause mutations cause mutations are called are called MUTAGENS.MUTAGENS.

Some examples are:Some examples are:1.1. Chemicals (Such as Chemicals (Such as

the ones in cigarette the ones in cigarette smoke)smoke)

2.2. Ultra-violet or Ultra-violet or ionizing radiationionizing radiation

3.3. VirusesViruses

Types of genetic Types of genetic mutations.mutations.

There are two main categories of mutation.There are two main categories of mutation. Point mutations and frame shift mutations.Point mutations and frame shift mutations.

In a point mutation, a single nitrogen base is In a point mutation, a single nitrogen base is substituted with another. substituted with another.

e.g. Normal gene =ATA CCG e.g. Normal gene =ATA CCG GGCA TTACA TTA

Mutated gene =ATA CCG Mutated gene =ATA CCG TTCA TTACA TTA

In this example, a guanine base has been In this example, a guanine base has been substituted with a thymine. substituted with a thymine.

Outcomes of point Outcomes of point mutationsmutations

There are three There are three possible possible outcomes of a outcomes of a point mutation.point mutation.

1.1. Silent mutationSilent mutation: : The mutated The mutated codon codes for codon codes for the same amino the same amino acid. The protein acid. The protein will be will be unchanged.unchanged.

For instance, if the For instance, if the codon AAA is codon AAA is mutated to AAG mutated to AAG there will be no there will be no difference in the difference in the the protein that is the protein that is translated. That is translated. That is because both AAA because both AAA and AAG code for and AAG code for the same amino the same amino acid.acid.

Point mutations cont.Point mutations cont.

2. Small change mutation(missense 2. Small change mutation(missense mutation)mutation): A single amino acid in a : A single amino acid in a protein will be different. The protein protein will be different. The protein will function, but not as well as an will function, but not as well as an unmutated one. Sickle-cell anemia is unmutated one. Sickle-cell anemia is the result of this type of point mutationthe result of this type of point mutation

In this disease, a codon which normally In this disease, a codon which normally would code for Valine is mutated into would code for Valine is mutated into one that codes for Glutamic Acid.one that codes for Glutamic Acid.

Point mutations (cont.)Point mutations (cont.)

3. 3. The stop command mutation The stop command mutation (nonsense mutations)(nonsense mutations): The mutation : The mutation causes a codon that would have causes a codon that would have coded for an amino acid to instead coded for an amino acid to instead code for the stop command. This code for the stop command. This will lead to incomplete protein will lead to incomplete protein fragments that will not function.fragments that will not function.

Types of genetic Types of genetic mutation (cont.)mutation (cont.)

2. Frame shift mutations: A nitrogen 2. Frame shift mutations: A nitrogen base is either added (insertion) or base is either added (insertion) or removed (deleted) from a gene.removed (deleted) from a gene.

Normal gene: ATA CGG CTA TTCNormal gene: ATA CGG CTA TTC

Insertion: ATA CGInsertion: ATA CGA A GCT ATT CGCT ATT C

Deletion: ATA CGC TAT TC Deletion: ATA CGC TAT TC

(a guanine was deleted)(a guanine was deleted)

Results of a frame shift Results of a frame shift mutationmutation

Except in the case of the stop command Except in the case of the stop command point mutation, frame shift mutations are point mutation, frame shift mutations are much worse than point mutations.much worse than point mutations.

In a gene that has been afflicted with a In a gene that has been afflicted with a frame shift mutation, it is unaffected frame shift mutation, it is unaffected prior to the location of the mutation, but prior to the location of the mutation, but then completely garbled afterwards.then completely garbled afterwards.

Lets look at an analogy to help illustrate Lets look at an analogy to help illustrate this.this.

Frame shift analogyFrame shift analogy

Consider the following sentence:Consider the following sentence: ““The fat cat sat and ate rat”. The fat cat sat and ate rat”. This represents the normal gene. Each This represents the normal gene. Each

3-letter word represents a codon in the 3-letter word represents a codon in the gene.gene.

Now let us consider what happens in an Now let us consider what happens in an insertion mutation. Lets insert a “a” insertion mutation. Lets insert a “a” between the t in “cat” and the s in “sat”.between the t in “cat” and the s in “sat”.

The gene would now look like thisThe gene would now look like this

Insertion cont.Insertion cont.

The fat cat The fat cat aasa tan dat era tsa tan dat era t

As you can see, the portion of the As you can see, the portion of the gene before the insertion is gene before the insertion is unchanged, but from the location of unchanged, but from the location of the insertion onwards, the gene is the insertion onwards, the gene is now nonsense.now nonsense.

This gene will not translate into a This gene will not translate into a useable protein.useable protein.

DeletionDeletion

A deletion also causes a frameshift, A deletion also causes a frameshift, and just like in an insertion, and just like in an insertion, everything from that point will be everything from that point will be altered.altered.

Let’s delete the S from sat in our Let’s delete the S from sat in our example.example.

Now it looks like this.Now it looks like this. The cat ata nda atr atThe cat ata nda atr at

Can mutations be passed on Can mutations be passed on to your children?to your children?

Yes, but only if the occur in the Yes, but only if the occur in the sperm or egg cells. sperm or egg cells.

These types of cells are referred to These types of cells are referred to as sex cells, or germ cells.as sex cells, or germ cells.

Mutations that occur in your body Mutations that occur in your body cells, which are also known as cells, which are also known as somatic cells, are not passed on to somatic cells, are not passed on to your children.your children.