Gene Mutations and Their Effects

Gene Mutations

  • A gene mutation is a permanent change in the sequence of bases in DNA.
  • The effects of a gene mutation can range from no effect on protein activity to complete inactivation of the protein.
  • Germ-line mutations occur in sex cells.
  • Somatic mutations occur in body cells.

Causes of Mutations

  • Spontaneous mutations are due to:
    • Chemical changes in DNA that lead to mispairing during replication.
    • Movement of transposons from one chromosomal location to another.
    • Replication Errors. DNA polymerase proofreads new strands and generally corrects errors. Overall mutation rate is 1 in 1,000,000,000 nucleotide pairs replicated. \frac{1}{1,000,000,000} is the mutation rate.
  • Induced mutations are caused by mutagens such as radiation and organic chemicals.
    • Many mutagens are also carcinogens (cancer-causing).
  • Environmental Mutagens
    • Food
    • Tobacco smoke

The Ames Test for Mutagenicity

The Ames test tests if suspected chemicals are mutagens. The test uses a bacterial strain that requires histidine. The bacteria are plated onto petri plates that lack histidine. If bacterial growth occurs, then a mutation occurred. A control is used with the bacterial strain that requires histidine to compare results.

Effect of Mutations on Protein Activity

  • Point mutations
    • One type of point mutation is a base substitution.
    • Involves a change in a single DNA nucleotide.
    • Change one codon to a different codon.
    • Effects on the protein vary:
      • Nonfunctional
      • Reduced functionality
      • Unaffected
  • Frameshift mutations
    • One or two nucleotides are either inserted or deleted from DNA.
    • The protein is always rendered nonfunctional.
    • Normal: THE CAT ATE THE RAT
      • After deletion: THE ATA TET HER AT
      • After insertion: THE CCA TAT ETH ERA T

Point Mutations

  • Normal DNA: TAC GAA ATT GGC TT
  • Normal mRNA: AUG CUU UAA CCG AA
  • Normal Amino acids: Met, Leu
  • Base substitution
    • DNA: TAC GAA ATT GGC TT
    • mRNA: AUG CUU UAA CCG AA
    • Amino acids: Met, Leu, Ile, Ala, Lys
  • Addition
    • DNA: TACA A ATT G
    • mRNA: UGU UUA AUC G
    • Amino acids: Met, Phe
  • Deletion
    • DNA: TACA
    • mRNA: AUG
    • Amino acids: Met

Point Mutation in Hemoglobin

  • Point mutations can affect Hemoglobin production and can lead to diseases such as cancer.

Nonfunctional Proteins

  • If a faulty enzyme is inserted into a metabolic pathway, a person may be unable to convert one molecule to another with serious consequences.
    • In the disorder phenylketonuria (PKU), phenylalanine builds up in the system and the excess causes an intellectual disability.
    • In androgen insensitivity, cells are unable to respond to testosterone due to a faulty receptor for testosterone.
      • Female instead of male genitals form, and female instead of male secondary sex characteristics occur at puberty.

Mutations Can Cause Cancer

  • Development of cancer involves a series of accumulating mutations.
  • Proto-oncogenes stimulate cell division. Mutated proto-oncogenes become oncogenes that are always active.
  • Tumor suppressor genes inhibit cell division.
  • Mutations in oncogene and tumor suppressor genes:
    • Stimulate the cell cycle uncontrollably.
    • Lead to tumor formation.