Gene Mutation

• Science
• Secondary Education

Teacher: We've been talking about this a lot in our previous lessons, can anyone explain what the central dogma of biology is? 

Answer: the central dogma of molecular biology is a theory that explains how genetic information (DNA) can be used to make RNA (through transcription) that then can be translated  to make new proteins. 

 Mutations 

Biology 30 

Molecular Genetics

Teacher: Hi all, welcome to biology 30. Today we will be learning about genetic mutations but before we do that let's review the concept of central dogma (go to slide 1). 

What do all of these have in common? 

They are mutants just like us! 

What is a Mutation?

• Mutations are permanent changes in the sequence of the DNA molecule. 
• Individuals showing these changes are known as mutants 
• Mutations are the source of new genetic variation that may be acted on by natural selection. 

• Point three 
  

Teacher: we talked about natural selection and the 5 mechanisms of it, if you remember, mutation is one of them. 

What Causes Mutations? 

Spontaneous mutations: mutations that occur as a result of errors made in DNA replication. 

•  DNA polymerase occasionally misses or misplaces a base during replication. 
  

Induced Mutations: arise from exposure to mutagenic agents

•  UV radiation, X-Rays and certain chemicals 
  

Point 1

Teacher: DNA polymerase have the ability to proofread and fix the errors but sometimes errors are not caught, resulting in mutations to occur. 

How Common are Mutations? 

-Several studies suggest that the overall rate of base substitutions in humans is about 1 x 10^-8 mutations per base pair per generation 

Are mutations harmful?

Yes

No

Both

18:10 - 20:42

Ask students: is anyone lactose intolerant? 

Mutations can be harmful

• A harmful mutation reduces an individual’s fitness and tends to be selected against. Harmful mutations occur at low rates in a species.

Mutations can be beneficial 

•  A beneficial mutation gives an organism a selective advantage and tends to become more common over time, leading to new evolutionary changes. 
  

Mutations may have no effect on the organism 

• having neither a benefit nor a cost, and are not acted on by natural selection.

Teacher: a common misconception that students often have is that they believe mutations are harmful but in reality, mutations can be harmful, beneficial, or have no effect on the organism 

• negative connotation associated with "mutated" it is important to recognize that not all mutations are harmful. In reality, majority of gene mutations are neutral or silent. 

As we saw in the video, mutations that give rise to new traits allows natural selection to act upon it. 

Types of Mutations 

Point Mutation 

Point Mutations: changes in a single or few base pair of a DNA sequence 

1.  Involves the substitution of one nucleotide for another 
2. Or the insertion/deletion of one or more nucleotides 
3. Results in silent, missense, nonsense or frameshift mutations 

Teacher: For this course, we're going to focus on point mutation 

In the next few slides, we're going to go over the effects of these mutations 

Silent Mutation: a mutation that does not result in a change in the amino acid coded for. 

• Has no effect on the operation of the cell and do not affect protein structure 

Silent mutations occurs when a base substitution does not cause a new amino acid to be coded for. 

This outcome is more likely to happen. 

Teacher: a mutation occurs in the G base of the template strand, G is substituted to A. Causes the complementary bases pairing to change and the mRNA sequences also changes but when it is translated into a protein, the amino acid does not change. 

Missense Mutation: arises when a change in a the base sequence of DNA alters a codon

• leading to a different amino acid being placed in the polypeptide 

Missense mutation arises when a substitution in the base sequence of DNA causes a change in the amino acid coded for. 

Nonsense mutation: occurs when a change in the DNA sequences causes a stop codon to replace a codon specifying an amino acid. 

- results in premature stop signal where a large protein could be missing if the nonsense mutation course early in the mRNA

Nonsense mutation occurs when the base substitution codes for a new amino acid that causes  introduces a premature stop during translation. 

Deletion: occurs when one ore more nucleotides are removed from the DNA sequence 

Insertion: the placement of an extra nucleotide in the DNA sequence 

Deletion and insertion causes changes in the reading frame called a frameshift mutation 

Base substitutions can result in silent, nonsense or missense mutations. 

On the other hand, deletion and insertions causes frameshift mutation. 

• remember that the nucleotides are read in triplets 

Insertion

Is This a Nonsense Mutation?

YES

NO

No. the insertion of a single nucleotide at this position shifts the reading frame and results in the premature stop. 

Deletion

The deletion of a single nucleotide at this position shifts the reading frame and results in "wrong" amino acids and a longer polypeptide 

All nucleotides downstream of a frameshift mutation will be improperly grouped into codons 

unless the frameshift is near the end of the gene, these mutations usually results in completely non-functional proteins 

what happens when three extra nucleotides is added or deleted to the DNA sequences? 

results in the addition or removal of one amino acid since the DNA sequence is read in triplet of nucleotides 

Sickle cell anemia 

caused by a single base pair substitution in the gene that codes the B hemoglobin polypeptide 

affects the 7th codon, Glu changed to Val 

the hemoglobin still functions but it folds differently, changing the shape of the rbc 

example of missense mutation 

Interesting fact: 

individuals that are heterozygote for sickle cell anemia have a survival advantage against malaria over people with with homozygote (two copies of the mutation) in regions where malaria is endemic or severe. 

Induced Mutations: are caused by mutagens 

• Factor or agents causing mutations are known as mutagens (physical or chemical) 
  

e.g. 

UV radiation 

X-rays

 Gamma-rays

Benzene - increases chance of leukaemia and other cancers 

 

mutagens fall into two general categories: physical and chemical 

Benzene is a chemical that increases chances of getting leukaemia and other cancer. 

Chemical Mutagens 

is a molecule that can enter the nucleus of a cell and induce mutations by reacting chemically with the DNA 

• a chemical mutant may act by inserting itself into the DNA molecule that causes a nucleotide substitution or a frameshift mutation 
  

most chemical mutagens are carcinogenic- they are associated with on for more forms of cancer 

Cigarette smokes contains many carcinogen(60+)  that increases mutation rate 

We often talk about how science processes impact the environment but it is also important to recognize how environmental factors affect our body and health. So it is essential that we understand how it impacts us and to make good choices. 

Physical Mutagens 

UV radiation: cause a chemical reaction between adjacent pyrmidine C + T bases. Result in a distortion in the DNA molecule that interferes with replication. Damage from UV radiation, as a result of exposure to sunlight, is a known cause of melanoma, a form of skin cancer. 

1. a single sunburn doubles a light-skinned person's chances of developing skin cancer 

1. Necessary for Evolution: Source of all genetic variation, which further provides the raw material for evolution

2. Cause of many diseases and disorders

• Huntington's Disease, Sickle Cell Anemia

mutations are both the sustainer of life and the cause of great suffering. on the one hand, mutations is the source of all genetic variation, the raw material of evolution. The ability of organisms to adapt to environmental change depends on the presence of genetic variation in natural populations and genetic variation is produced by mutation. On the other hand, many mutations have detrimental effects, and mutation is the source of many diseases and disorders.