upgrade
upgrade

🐾General Biology II

Types of Gene Mutations

Study smarter with Fiveable

Get study guides, practice questions, and cheatsheets for all your subjects. Join 500,000+ students with a 96% pass rate.

Get Started

Why This Matters

Gene mutations are the molecular foundation of everything from evolutionary change to inherited disease—and you're being tested on your ability to distinguish how different mutations alter protein synthesis and why some are devastating while others go unnoticed. The key principles at play here include the reading frame, codon redundancy, and the relationship between DNA sequence and protein function. These concepts connect directly to central dogma, protein structure, and the genetic basis of phenotypic variation.

Don't just memorize a list of mutation types. For each one, know what happens at the molecular level, what the likely outcome is for the protein, and when that mutation type would show up as an example in an FRQ about evolution, disease, or gene expression. The comparisons between mutation types—especially why a silent mutation differs from a missense mutation despite both being point mutations—are exactly the kind of distinctions that separate strong exam responses from weak ones.


Point Mutations: Single Nucleotide Changes

Point mutations involve the substitution of just one nucleotide for another. Because the genetic code is degenerate (redundant), the consequences of a single-base change depend entirely on where it occurs and what codon it creates.

Silent Mutations

  • No change to the amino acid sequence—the new codon still codes for the same amino acid due to wobble position redundancy
  • Often occur at the third position of a codon, where multiple codons specify the same amino acid
  • Generally no phenotypic effect, though some can subtly influence mRNA stability or splicing efficiency

Missense Mutations

  • Substitution of one amino acid for another—the new codon specifies a different amino acid in the polypeptide chain
  • Effects range from neutral to lethal depending on whether the substituted amino acid has similar or different chemical properties
  • Classic example: sickle cell anemia—a single glutamic acid → valine substitution alters hemoglobin structure and function

Nonsense Mutations

  • Creates a premature stop codon—converting an amino acid codon (like UAG, UAA, or UGA) halts translation early
  • Results in truncated proteins that are typically nonfunctional and often degraded by the cell
  • Frequently causes severe genetic disorders because the protein product is completely lost or dysfunctional

Compare: Silent vs. Missense vs. Nonsense mutations—all three are point mutations involving a single nucleotide change, but outcomes differ dramatically based on codon consequences. If an FRQ asks you to explain why some mutations are harmful and others aren't, this trio is your go-to example of how context determines effect.


Frameshift Mutations: Disrupting the Reading Frame

Frameshift mutations occur when insertions or deletions shift the triplet reading frame of mRNA. Because codons are read in non-overlapping groups of three, adding or removing nucleotides that aren't multiples of three changes every downstream codon.

Insertions

  • Addition of one or more nucleotides to the DNA sequence disrupts the normal reading frame
  • All downstream amino acids are altered—the ribosome reads completely different codons from the mutation point onward
  • Can occasionally create gain-of-function mutations if the new sequence produces a protein with novel activity

Deletions

  • Removal of one or more nucleotides shifts the reading frame just like insertions do
  • Typically results in nonfunctional proteins because the entire amino acid sequence downstream is scrambled
  • Loss-of-function outcome is more common than gain-of-function due to random sequence disruption

Frameshift Mutations (General Category)

  • Caused by insertions or deletions not in multiples of three—if you add or remove 3, 6, or 9 nucleotides, the reading frame is preserved
  • Often introduce premature stop codons because the shifted frame eventually reads a stop codon by chance
  • Among the most severe mutation types because they affect not just one amino acid but the entire downstream sequence

Compare: Insertions vs. Deletions—both cause frameshifts through opposite mechanisms (adding vs. removing nucleotides), but the downstream effect is identical: complete alteration of the amino acid sequence. Remember that insertions or deletions in multiples of three avoid frameshift effects entirely.


Chromosomal Mutations: Large-Scale Rearrangements

These mutations involve segments of chromosomes rather than individual nucleotides. The consequences depend on whether genes are disrupted, duplicated, or placed under new regulatory control.

Chromosomal Translocations

  • Rearrangement of segments between non-homologous chromosomes—pieces of different chromosomes swap positions
  • Can create fusion genes where parts of two different genes are joined, producing hybrid proteins with altered functions
  • Strongly associated with cancers—the Philadelphia chromosome (BCR-ABL fusion) in chronic myeloid leukemia is a classic example

Inversions

  • A DNA segment is reversed 180° within the chromosome—the sequence reads backward relative to its original orientation
  • May disrupt genes or regulatory elements at the breakpoints where the inversion occurred
  • Can suppress recombination in heterozygotes, which has implications for maintaining certain allele combinations in populations

Duplications

  • Copying of a DNA segment results in multiple copies of genes or regulatory regions
  • Gene dosage effects can occur when extra copies produce excess protein, disrupting cellular balance
  • Evolutionary significance—duplicated genes can diverge over time, with one copy maintaining original function while the other evolves new capabilities

Compare: Translocations vs. Inversions—both are chromosomal rearrangements, but translocations involve different chromosomes while inversions occur within a single chromosome. Translocations are more likely to create problematic fusion genes; inversions are more likely to affect recombination patterns.


Quick Reference Table

ConceptBest Examples
Single nucleotide changesSilent, Missense, Nonsense mutations
Reading frame disruptionInsertions, Deletions, Frameshift mutations
Codon redundancy effectsSilent mutations
Premature terminationNonsense mutations, Frameshift mutations
Protein structure alterationMissense mutations
Large-scale chromosomal changesTranslocations, Inversions, Duplications
Cancer associationsTranslocations, Duplications
Evolutionary raw materialDuplications, Missense mutations

Self-Check Questions

  1. Which two mutation types both result in premature stop codons, and how do they arrive at this outcome differently?

  2. A mutation adds two nucleotides to a gene. Another mutation adds three nucleotides to a different gene. Which is likely to have more severe consequences, and why?

  3. Compare and contrast missense and silent mutations: both are point mutations, so what determines whether the amino acid sequence changes?

  4. If an FRQ asks you to explain how gene duplications contribute to evolution, what mechanism would you describe and what example could you use?

  5. A patient has chronic myeloid leukemia caused by the Philadelphia chromosome. What type of mutation is this, and what molecular event created the disease-causing gene?