Lesson 1 of 9 / Mutation, cell division and cancer
Substitutions and frameshifts
Why can adding one base have a larger effect than changing one base?
I can explain sequence mutations and their possible amino-acid consequences.
I can explain gene mutations and numerical/structural chromosome aberrations.Syllabus
Syllabus 9477, Core 2(k). Explain gene mutations and numerical/structural chromosome aberrations.
About 7 min
Make a guess. You are not marked.
Which usually changes a protein more: substituting one base, or inserting one extra base?
Show the answer
Inserting one, because it shifts the frame.
An insertion changes every codon after it. A substitution changes one codon, and may even be silent.
The key idea
A substitution changes one position; an insertion or deletion can shift every downstream codon unless the change preserves the reading frame.
Explore the idea
Regroup the message after a change
Read from the same start. Bars mark codon boundaries, not bonds in the RNA.
RNA sequences display consequences of corresponding DNA changes. The incomplete final group is a fragment at the edge of this short example, not an extra complete codon.
Explanation
A gene mutation changes the nucleotide sequence of a gene. A substitution replaces one base with another. In a coding region it may be silent because the new codon specifies the same amino acid, missense because it specifies another amino acid, or nonsense because it becomes a stop codon.
An insertion or deletion adds or removes bases. If the number changed within the translated region is not a multiple of three, the downstream reading frame shifts. Subsequent codons change and an early stop may occur, often producing a substantially altered product. A three-base change can add or remove an amino acid without a downstream frameshift.
The effect depends on location as well as mutation type. A non-coding regulatory change can affect expression amount; a coding change may alter an active site or have little functional effect. A mutation does not automatically produce a visible phenotype.
Mutations can arise during copying or after DNA damage. Their occurrence is not directed towards what an organism needs. In sexual reproduction, a mutation must reach the germ line to be transmitted through gametes; a mutation restricted to a body-cell lineage is not inherited by offspring that way.
Step by step
- 1
Locate the coding frame
Group the original RNA into triplets from the specified start.
- 2
Apply the change once
Do not change unrelated bases.
- 3
Regroup and compare
Separate altered codons from unchanged upstream sequence.
Worked example
Work through the evidence
Original RNA is AUG AAA GGC UAA. Insert C after AUG. Compare the next codons.
One way to explain it
The changed sequence begins AUG CAA AGG CUA... instead of AUG AAA GGC UAA. The insertion shifts grouping downstream of the insertion.
Why this answer works
- The first AUG remains unchanged.
- A single added base changes the downstream reading frame rather than merely adding one complete amino acid.
Watch out for this
A student says: "Every substitution changes the amino acid." What is wrong with this?
Show the answer
The genetic code is degenerate, so some substitutions are silent at the amino-acid level.
Check your understanding
Which change preserves the downstream reading frame most directly?
Show the answer
Deletion of three consecutive coding bases
It can remove one amino-acid position without shifting all later triplet grouping, although the protein may still be affected.
Quick recall
Why can adding one base have a larger effect than changing one base?