DNA Mutations

What is a mutation?

A mutation is a change in the DNA sequence. It can involve a single nucleotide (point mutation) or larger segments of DNA, such as insertions, deletions, or duplications.

How does a mutation lead to an altered protein function?

The pathway is as follows:

• Change in DNA sequence
• Potential change in mRNA sequence
• Potential change in amino acid sequence (primary structure)
• Alteration of protein folding and structure
• Change or loss of protein function

Silent Mutation

A point mutation that changes a DNA base but does not change the amino acid due to the redundancy of the genetic code. These usually have no effect on protein structure or function.

Missense Mutation

A mutation that changes one amino acid in the protein. The severity depends on the substitution:

• Conservative change: The new amino acid is similar to the original; likely a small effect.
• Non-conservative change: The new amino acid is very different; may disrupt folding/activity (e.g., Sickle cell anemia where glutamic acid \rightarrow valine).

Nonsense Mutation

A change in a DNA base that converts a codon into a stop codon. This results in a shortened (truncated) protein that is often completely nonfunctional.

Frameshift Mutation

Occurs when nucleotides are added or removed in quantities not in multiples of 3. This shifts the reading frame, changing every amino acid downstream and typically resulting in a nonfunctional protein.

In-frame Insertions and Deletions

The addition or removal of nucleotides in multiples of 3. This adds or deletes specific amino acids without shifting the reading frame, but it can still disrupt the protein's shape or active sites.

How is Tertiary Structure specifically affected by mutations?

Misfolding can occur at the tertiary level if mutations alter:

• Charges: Affecting electrical attraction or repulsion.
• Hydrophobicity: Misplacing hydrophobic amino acids.
• Disulfide bonds: Preventing or creating inappropriate covalent links.

What functional aspects of a protein can be altered by structural changes?

1. Active site shape: Inhibits substrate binding.
2. Binding affinity: Changes the strength of interactions.
3. Stability: Protein may break down faster.
4. Localization: Protein may not reach the correct cellular location.
5. Regulation: Protein may become overactive or inactive.

Quaternary Structure Disruption

In proteins consisting of multiple subunits, a mutation that causes a fault in a single subunit