Microbiology 2 - 2.5 - Mutations

What are mutations?

Any changes in the nucleotide sequence of DNA; genetic variation that drives evolution

Mutations can be...

Advantageous, Deleterious, Neutral

What are examples of advantageous mutations?

- Lactase persistence (metabolize lactose)

- Leads to further evolution

What are examples of deleterious mutations?

- Cystic fibrosis (buildup of mucus in the lungs)

- Decreases fitness in an organism, can lead to death

What are examples of neutral mutations?

- Eye color (blue)

- Adds diversity

What are the two categories of mutations?

1. Substitutions (point mutations)

2. Insertions or deletions

When do substitutions occur?

When a single base is changed

What are specific examples of substitutions?

1. Silent mutations

2. Missense mutations

3. Nonsense mutations

What are silent mutations?

They do not alter the amino acid sequence; no affects are seen

What are missense mutations?

- They DO alter the amino acid sequence of a polypeptide

- Can be defective (non-functional protein) in which a new amino acid is chemically different from the original (ex: sickle cell)

- Can be functional in which a new amino acid is chemically similar from the original amino acid

What are nonsense mutations?

Result in the conversion of an amino acid to a stop codon; typically lead to a non-functional protein

When do insertions/deletions occur?

When one or more bases are added/removed from a DNA sequence

What are frameshift mutations?

A type of insertion/deletion; result in an altered reading frame of the DNA sequence

What is the reading frame?

Coding portion in a genome (from start to stop codon)

If the reading frame is shifted, we will see...

A complete change in every amino acid produced (dramatic altering of amino acid sequence to result in non-functional proteins)

What are examples of other chromosomal mutations?

Inversions and translocations

What are inversions?

Changes in which a section of DNA is inverted and reinserted into the genome (large chunks of the genome are moved around, the order of genes are changed)

What are translocations?

Changes in which a segment of a chromosome breaks off and reattaches to a different location (moving between different chromosomes)

How do mutations occur?

- DNA polymerase has strong fidelity but mutations occur every 1 in 1 billion bases

- Mutagens increase the rate of mutation

What are the two types of mutagens?

- Chemical - alter base pairing rules

- Physical - high energy wavelengths on electromagnetic spectrum

What are two types of chemical mutagens?

- Nitrous acid

- Methyl-nitrosoguanidine

What does nitrous acid do?

Deaminates; removes amino group (NH2) from amino acids

When adenine is deaminated, what does it result in?

Hypoxanthine, which pairs with Cytosine

When cytosine is deaminated, what does it result in?

Uracil, which pairs with Adenine

When guanine is deaminated, what does it result in?

Xanthine, which pairs with cytosine

What does Methyl-nitrosoguanidine do?

Methylates; adds methyl group (CH3)

When guanine is methylated, it base pairs with...

Thymine

What are two types of physical mutagens?

- UV light (non-ionizing radiation)

- Ionizing radiation (x rays, gamma rays)

What does UV light do?

Forms thymine dimers; distort the DNA molecule which then leads to replication errors (mutations)

What does ionizing radiation do?

- Causes ss or ds breaks in the DNA, which are caused by hydroxyl-radicals

- Can sometimes modify bases similar to nitrous acid (deamination)

What are hydroxyl-radicals?

Highly unstable and reactive molecules that steal electrons from DNA

What are ways mutations are repaired?

- DNA pol 3' to 5' exonuclease proofreading activity

- Mismatch repair systems

- Photolyase

- Alkytransferase

- DNA glycosylase

What does the DNA pol 3' to 5' exonuclease proofreading activity do?

- Identifies and removes incorrect bases within a growing chain

- When it is missed, this leads to the 1 in 1 billion bp mutation

What does the mismatch repair systems do?

- Occurs if DNA pol doesn't repair the mistakes

- Excise several bases around the mismatched base; fills in the gaps with correct bases and links together adjoining fragments

What does photolyase do?

- Only works in presence of visible light

- Cleaves covalent bonds causing thymine dimers; cuts bond between them

What does Alkytransferase do?

Repairs methylation caused by methyl-nitrosoguanidine (removes methyl groups)

What does DNA glycosylase do?

Enzyme that recognizes damaged bases and initiates base excision repair