DNA mutations

Mutation (definition)

A change in the nucleotide sequence of the genetic material.

Role of Mutations in Life

Mutations provide genetic variation; can be beneficial (>1%—SNPs) for evolution or harmful (<1%), often causing disease.

Why mutations matter

They are essential for evolution but often detrimental to individuals; organisms evolved DNA repair mechanisms.

Germ-line mutation

A mutation occurring in sperm, egg, or precursor cells; can be passed on to future generations.

Somatic mutation

A mutation in any non-reproductive body cell; cannot be inherited.

Chromosomal mutation

A change in chromosome structure.

Genomic mutation

A change in chromosome number.

Single-gene mutation

Small sequence changes within a specific gene (focus of lecture).

Point mutation

A change in a single base pair involving a base substitution.

Transition mutation

A purine → purine (A↔G) or pyrimidine → pyrimidine (C↔T) substitution. More common.

Transversion mutation

A purine ↔ pyrimidine substitution (A/G ↔ C/T). Less common.

Regulatory mutation

A mutation affecting the level or production of gene product (promoters, splice sites, ribosome binding sites).

Structural (coding) mutation

Mutation affecting the amino acid sequence of the gene product.

Silent mutation

Base substitution that does not change the amino acid due to codon degeneracy (e.g., GAA→GAG: Glu→Glu).

Missense mutation

Base substitution that changes the amino acid (e.g., GAG→GTG: Glu→Val). May be neutral or harmful depending on chemical similarity.

Nonsense mutation

A mutation converting a codon into a stop codon (UAG, UAA, UGA), causing early termination of translation.

Insertion mutation

Addition of nucleotides into DNA; depending on number, may cause frameshift.

Deletion mutation

Removal of nucleotides from DNA; may cause frameshift.

Frameshift mutation

Insertion/deletion not divisible by 3; alters reading frame, producing extensive missense or premature stop codons; usually produces a nonfunctional protein.

Wild-type

The most prevalent genotype in a natural population.

Forward mutation

A change from wild-type to mutant allele.

Reverse mutation (reversion)

A change from mutant allele back to wild-type (e.g., AAA→AGA→AAA).

Variant (phenotypic definition)

An organism whose phenotype is altered by a mutation.

Conditional mutant

A mutation causing phenotype changes only under specific conditions (e.g., temperature-sensitive lethal at high temp).

Causes of mutations (chemical)

Oxidation, hydrolysis, and methylation can chemically alter DNA.

Stop codons

The three stop codons: UAG, UAA, UGA.

Effect of nonsense mutation

Translation stops early; release factor binds instead of tRNA; produces smaller protein.

Frameshift consequences

Usually creates a drastically altered protein sequence; often nonfunctional or unstable.