Genetic Mutations: Indels and Point Mutations – OCT 29

Genetic Mutations

Overview of Mutations

Genetic mutations are changes in the DNA sequence that can affect gene function and protein synthesis. Two major classes of mutations are insertions/deletions (indels) and point mutations (substitutions). These mutations can have varying effects on the encoded protein, depending on their nature and location.

• Insertions/Deletions (Indels): Addition or removal of one or more nucleotides in the DNA sequence.

• Point Mutations (Substitutions): Replacement of a single nucleotide with another.

Insertions and Deletions (Indels)

Frameshift Mutations

Indels that are not in multiples of three nucleotides cause frameshift mutations, altering the reading frame of the gene and changing the downstream amino acid sequence.

• Frameshift Mutation: Occurs when the number of inserted or deleted nucleotides is not a multiple of three.

• Effect: Alters the entire amino acid sequence downstream of the mutation, often resulting in a nonfunctional protein.

Example:

• Original: THE CAT SAW THE DOG

• Deletion (Loss of one letter): THE ATS AWT HED OG

• Insertion (Gain of one letter): THE CMA TSA WTH EDO G

Local Indel Effects

Indels in multiples of three nucleotides do not cause frameshifts but may result in the addition or loss of amino acids, potentially affecting protein function locally.

• Local Effect: Addition or deletion of amino acids without altering the reading frame.

Point Mutations

Definition and Types

A point mutation is a change in a single nucleotide of DNA. These mutations can be classified based on their effect on the protein:

• Missense Mutation: Codon change results in a different amino acid.

• Nonsense Mutation: Codon change converts an amino acid codon to a stop codon, terminating translation prematurely.

• Sense Mutation: Stop codon is converted to a codon for an amino acid, extending the protein.

• Silent Mutation: Codon change does not alter the amino acid due to the redundancy of the genetic code (wobble position).

Example:

• Original: THE CAT SAW THE DOG

• Substitution: THE BAT SAW THE DOG (missense)

• Substitution: THE CAT SAW THE HOG (missense)

• Substitution: THE CAT SAT THE DOG (missense)

Genetic Code and Mutation Effects

The effect of a point mutation depends on the codon change and the genetic code. The third position of the codon (wobble position) often allows for silent mutations.

• Missense: Alters amino acid sequence.

• Nonsense: Introduces premature stop codon.

• Silent: No change in amino acid sequence.

Examples of mRNA Mutations

Reading Frame Analysis

Mutations in mRNA can be analyzed by comparing the wild-type and mutant sequences:

• Wild-type mRNA: 5'-AUGUCUCGUACCGGGACUUAG-3'

• Mutant mRNA #1: 5'-AUGUCUCGUGACCGGGACUUAG-3'

Depending on the change, the mutation may be classified as missense, nonsense, frameshift indel, silent, or local indel.

Summary Table: Types of Point Mutations

Type	Definition	Effect on Protein	Example
Missense	Codon change results in different amino acid	Altered protein sequence	THE BAT SAW THE DOG
Nonsense	Codon change creates stop codon	Premature termination	THE CAT SAW THE (stop)
Sense	Stop codon converted to amino acid codon	Extended protein	Additional info: Example not shown in slides
Silent	Codon change does not alter amino acid	No change in protein	THE CAT SAW THE DOG

Key Terms

• Indel: Insertion or deletion of nucleotides.

• Frameshift: Mutation that shifts the reading frame.

• Missense: Mutation resulting in a different amino acid.

• Nonsense: Mutation resulting in a stop codon.

• Silent: Mutation with no effect on amino acid sequence.

Additional info:

• Silent mutations often occur at the third base of a codon due to the degeneracy of the genetic code (wobble position).

• Frameshift mutations are typically more severe than point mutations because they alter the entire downstream protein sequence.