Consequences of Insertions and Deletions
- Insertions add extra nucleotides into the DNA sequence.
- Deletions remove nucleotides from the DNA sequence.
- Both disrupt the genetic code, often with severe consequences.
Frameshift Mutations: A Domino Effect
- DNA is read in triplets called codons, each coding for a specific amino acid.
- Inserting or deleting a nucleotide shifts the reading frame, altering every codon downstream.
- Frameshifts are not the same as substitutions.
- Substitutions affect only one codon, while frameshifts disrupt the entire sequence.
If the insertion or deletion occurs near the start of the gene, the effects are usually more severe because most of the protein is altered.
Major Insertions and Deletions: Structural Chaos
- Larger insertions or deletions (multiples of three) don’t cause frame shifts but still disrupt protein function.
- They add or remove entire amino acids, altering the protein’s shape and stability.
- Imagine a zipper missing several teeth.
- It might still work, but not as efficiently or reliably.
Consequences of Major Changes
- Loss of Function: The protein may become unstable or unable to bind to other molecules.
- Gain of Function: Rarely, these mutations create new functions, but they are usually harmful.
Even if the reading frame is preserved, the addition or removal of amino acids can disrupt critical regions of the protein, such as active sites or binding domains.
Why Insertions and Deletions Are Rarely Beneficial
- Most mutations are neutral or harmful because genes have evolved to perform specific functions.
- Random changes are unlikely to improve these finely tuned systems.
- How do we balance the risks and benefits of mutations in evolution?
- Could a harmful mutation today lead to a beneficial adaptation in the future?
Exceptions: When Insertions or Deletions Don’t Cause Frameshifts
- If the number of nucleotides added or removed is a multiple of three, the reading frame is preserved.
- However, the protein still gains or loses amino acids, which can disrupt its function.
A deletion of three nucleotides might remove an amino acid essential for the protein’s stability or activity.
Self reviewWhat is the difference between a frameshift mutation and a non-frameshift mutation? How do their effects on protein function differ?
Likelihood of Polypeptides Ceasing to Function
- Frameshift Mutations: Highly likely to produce nonfunctional proteins due to widespread changes in the amino acid sequence.
- Major Insertions/Deletions: Often result in loss of function by disrupting the protein’s structure or removing critical regions.
- Think of a polypeptide as a carefully constructed building.
- A frameshift mutation is like removing a foundation pillar, causing the entire structure to collapse.
- A major insertion or deletion is like adding or removing a wall—it may not collapse the building, but it can severely weaken it.
Reflection and Broader Implications
- Insertions and deletions highlight the precision required for genetic stability.
- They also underscore the role of mutations in evolution, where even harmful changes can drive diversity over time.
- How does our understanding of mutations influence ethical debates about gene editing?
- Should we intervene to prevent harmful mutations, or is genetic variation too important for evolution?
- Why are frameshift mutations generally more harmful than base substitutions?
- Can you think of a scenario where a deletion might be beneficial?
