Genetic Mutations Overview

Genetic Mutations

Definition

  • Genetic mutation: A heritable change in the nucleotide sequence of DNA. These mutations can alter the sequences of genes, potentially resulting in altered amino acid sequences.

Cell Types Involved in Mutations

  • Germ-line cells:
    • Unaffected by certain mutations; mutations in these cells can be passed to offspring.
    • Half of germ-line cells can carry mutations inherited from one parent.
  • Somatic (body) cells:
    • Mutations can occur in somatic cells during development or throughout an organism's life.
    • All somatic cells in an organism can carry mutations if they arise from a parental germ-line mutation.

Sources of Mutations

  1. Inherited Mutations: Mutations that are passed from parent(s) to offspring, typically arising in germ-line cells.
  2. Acquired Mutations: Mutations that occur during an individual's life and are not inherited. These arise:
    • Spontaneously, without a known mutagen.
    • Due to mistakes in DNA replication or due to faulty DNA repair mechanisms.
    • Following exposure to a mutagen, which is a physical or chemical agent inducing changes in nucleotide sequences.

Effects of Mutations on Protein Function

  • Nucleotide sequence change in a gene can lead to changes in the corresponding mRNA sequence, which may subsequently affect the amino acid sequence.

Types of Mutations

  1. Missense mutation: Results from nucleotide substitution, leading to a change in the identity of the amino acid.
  2. Silent mutation: Also results from nucleotide substitution, but does not change the identity of the amino acid.
  3. Nonsense mutation: A nucleotide substitution alters an amino acid into a stop codon, prematurely terminating the translation process.
  4. Frameshift mutation: Results from the insertion or deletion of a nucleotide, causing a shift in the reading frame during translation.

Detailed Impacts of Nucleotide Changes

Types of DNA Sequence Changes

  • Nucleotide substitution: One nucleotide is replaced by another.
  • Nucleotide insertion: An additional nucleotide is introduced into the DNA sequence.
  • Nucleotide deletion: A nucleotide is removed from the DNA sequence.

Examples of Nucleotide Substitution Outcomes

  • Missense mutation: Changes the identity of an amino acid (e.g., Ile to Gly):
    • Before Substitution: Original RNA sequence - Amino Acids: Ile, Asp, Val
    • After Substitution: RNA sequence - Amino Acids: Ile, Gly, Val (polar vs non-polar identity)
  • Silent mutation: No change in the identity of the amino acid (e.g., Ile to Ile results in the same amino acid sequence).
  • Nonsense mutation: Converts an amino acid to a stop codon:
    • Example: Original RNA with Ile, Arg, Arg; codon shifts to a stop signal, halting protein synthesis early.

Frameshift Mutations

  • Definition: Large changes arising from nucleotide insertion or deletion that alter the reading frame.
    • Example demonstrating nucleotide insertion leading to an altered reading frame:
    • Original DNA sequence: 11 nucleotides
    • After insertion: 12 nucleotides leading to change in ORF.

Open Reading Frames (ORFs)

  • Concept of ORFs: The ribosome reads mRNA in sets of three nucleotides (codons) to translate into an amino acid sequence.
  • There are three ORFs on a single mRNA strand.
  • Significance of Start Codon: Ribosomes utilize the open reading frame containing a start codon (AUG) to initiate protein synthesis. If no AUG appears in a frame, no protein will be produced.

Functional Impacts of Mutations

  • Mutations can lead to different functional consequences:
    • Gain of function mutation: A mutation that causes enhanced activity of a protein.
    • Loss of function mutation: A mutation reducing or eliminating the functional capability of a protein.

Connection to Disease

  • Genetic mutations can lead to medical conditions known as genetic disorders:
    • Inheritance: Genetic disorders can be inherited or acquired over a person's lifetime.
  • Example: Sickle Cell Disease:
    • Caused by a mutation in the β-globin gene (part of hemoglobin), resulting in abnormally shaped red blood cells (RBCs).
    • Consequences include blocked blood flow, anemia, and consequent tissue damage.