Gene Mutation and DNA Repair

Gene Mutation and DNA Repair

• Mutations are variations in DNA caused by mistakes during DNA copying, such as inserting the incorrect base or skipping a base.
• Mutations arise from the Latin word mutare, meaning "to change."
• Mutations are changes in the DNA nucleotide sequence, potentially causing heritable changes in genetic information.
• Organisms have evolved DNA repair mechanisms to counteract harmful mutations.

Types of Mutations

• Mutations are categorized as either gene mutations or chromosomal mutations.
• Gene mutations affect a single gene, while chromosomal mutations affect entire chromosomes.

Chromosomal Mutations

• Chromosomal changes involve alterations in chromosome structure or number, often impacting more than one gene.

Gene Mutations (Point Mutations)

• Point mutations affect one or a few nucleotides and occur at a single point in the DNA sequence.

• These mutations typically occur during DNA replication.

• A point mutation is a change in a single base pair involving a base substitution.

• A transition is a change of a pyrimidine (C or T) to another pyrimidine or a purine (A or G) to another purine.

• A transversion is a change of a pyrimidine to a purine or vice versa.

• Transitions are more common than transversions.

• Deletions or insertions of nucleotides can also cause a shift in the reading frame, affecting amino acid sequence.

Mutations in the Coding Sequence

• Silent mutations do not alter the amino acid sequence due to the degeneracy of the genetic code.
• Missense mutations alter the amino acid sequence, sometimes causing minimal impact, or potentially significant impact like in sickle-cell anemia.
• Nonsense mutations change a codon to a stop codon, resulting in a truncated polypeptide.
• Frameshift mutations occur when nucleotides are added or deleted in multiples of one or two, causing a shift in the reading frame and a change in the amino acid sequence downstream of the mutation.

Gene Mutations in Noncoding Sequences

• Mutations in noncoding sequences can alter gene expression.
• Promoter mutations can affect transcription rates.
• Mutations in splice junctions or 5' and 3' UTRs can affect mRNA stability and translation.
• Regulatory element/operator site mutations affect proper gene expression regulation.

Gene Mutations and Their Effects on Genotype and Phenotype

• Neutral mutations do not affect protein function.
• Deleterious mutations reduce the chances of survival and reproduction. Lethal mutations result in cell or organism death.
• Beneficial mutations enhance survival or reproductive success.
• Conditional mutations affect the phenotype only under specific environmental conditions.

Chromosomal Mutations

• Chromosomal mutations alter the number or structure of chromosomes, affecting gene location or copy number.
• Types of chromosomal mutations include: deletions, duplication, inversion and translocation.
• Deletion involves the loss of all or part of a chromosome, which is now unavailable for inheritance.
• Changes in chromosome structure can affect gene expression. This is called the position effect, and results from chromosomal rearrangement.
• Position effect results from movement to a position near regulatory sequences for a different gene and from movement to a heterochromatic region.

Mutations Can Occur in Germ-Line or Somatic Cells

• Geneticists categorize animal cells into germ-line (give rise to gametes) and somatic (all other cells) categories.
• Mutations in germ-line cells are found in the entire body of the organism, while mutations in somatic cells are restricted to a specific part, based on when the mutation occurred.

Causes of Mutation

• Mutations can be spontaneous, arising from abnormalities in cellular processes like errors in DNA replication, or induced, caused by environmental factors.
• Mutagens are agents that alter DNA structure.
• Spontaneous mutations arise due to three chemical changes: depurination, deamination and tautomeric shift.
• Induced mutations result from chemical and physical agents like ionizing radiation (X-rays, gamma rays) and nonionizing radiation (UV light).
• Different types of mutagens have different effects on DNA, which affect base pairing, nucleotide structure and can lead to mutations

DNA Repair

• Living organisms have multiple DNA repair systems to correct DNA alterations.
• DNA repair typically follows a multistep process: Detection of the irregularity. Removal of the damaged DNA. Synthesis of new normal DNA.
• Different types of DNA repair systems such as direct repair, nucleotide excision repair, mismatch repair, and recombination repair address different types of DNA damage.

Examples of Mutagens

• Nitrous acid, nitrogen mustard, and ethyl methanesulfonate are chemical mutagens that alter base structures.
• X-rays and UV light are physical mutagens that damage DNA structure.