Copying three billion bases without a single slip is impossible, and your cells do it over and over again. Mistakes happen. Most are corrected or harmless, but the ones that survive are called mutations — and there are three ways a base sequence can go wrong, with very different consequences.
📘 What you need to know
A gene mutation is a change in the base sequence of DNA, and it may produce a new allele.
Mutations happen all the time and at random, most often as copying errors during DNA replication in S phase of interphase.
A substitution swaps one base for another. It affects only the triplet it lands in.
An insertion adds a base and a deletion removes one. Both shift every triplet after that point — a frameshift.
Mutagens increase the mutation rate: high-energy radiation (UV), ionising radiation (X-rays, gamma rays, alpha particles), and chemicals such as those in tobacco smoke.
DNA polymerase proofreads as it replicates and replaces wrong nucleotides. Mutations survive when proofreading misses them.
Some regions mutate more than others. Exposed, uncoiled DNA and CpG sites are hotspots.
Cells have no mechanism for mutating on purpose. Mutation is never a response to need.
The three ways a sequence can change
Every gene is read in groups of three, so what matters is not just which base changed but whether the grouping survives.
Substitution — one base is swapped for a different one. The number of bases stays the same, so the triplets after it are untouched. Only one triplet is affected, so at most one amino acid changes.
Insertion — an extra nucleotide is added. Every base after it is pushed along by one, so all the following triplets are re-grouped.
Deletion — a nucleotide is lost. Everything after it is pulled back by one, and again the following triplets are re-grouped.
Insertions and deletions are the dangerous ones. This re-grouping is called a frameshift mutation, and it can change the whole rest of the polypeptide.
The bands never move — the cell always reads in threes from the same starting point. It is the letters that slide, and that is what does the damage.
Try it with a sentence. “THE BIG CAT SAW THE DOG” still makes sense if you swap one letter: “THE BIG CAR SAW THE DOG”. Now delete the H: “TEB IGC ATS AWT HED OG”. Nothing after the deletion means anything. That is a frameshift.
What causes mutations?
Some mutations arise from nothing more than the sheer volume of copying a cell does. Others are caused by things in the environment. Anything that raises the mutation rate is called a mutagen or a mutagenic agent.
Cause
Examples
How it acts
High-energy radiation
UV light
Causes chemical changes in the DNA molecule
Ionising radiation
X-rays, gamma rays, alpha particles
Damages bases and breaks the DNA strand
Chemical mutagens
Benzo[a]pyrene and nitrosamines in tobacco smoke; mustard gas
React with DNA and alter bases
Internal mutagens
Certain enzymes inside the cell
Break down DNA or make mutagenic substances
Copying errors
Replication and repair in S phase
A wrong nucleotide is added and missed by proofreading
This is the reason UV exposure and smoking are linked to cancer: more mutations means a greater chance that one lands in a gene controlling cell division.
Why most errors never become mutations
DNA polymerase does not just build new strands — it proofreads them. If it detects that the wrong nucleotide has been added, it removes it and replaces it before carrying on. A mutation only survives when that check misses the error.
Even then, most surviving changes do nothing. They may land in non-coding DNA, or the genetic code’s degeneracy may mean the amino acid is unchanged.
Random, but not evenly spread
Mutations can occur anywhere, in any organism, on any chromosome — that is how new strains of bacteria and viruses appear. But some places are more vulnerable than others:
Uncoiled DNA is more exposed than DNA wound tightly around a histone, so it is more likely to be hit.
Many mutations occur in non-coding regions such as satellite DNA, where they usually have no effect.
Mutation hotspots are regions that mutate unusually often. One is the CpG site, where a cytosine is followed by a guanine. When methylation occurs there, the C can change into a T. Where CpG sites cluster together they form a CpG island, and these are associated with certain cancers, including colorectal cancer.
No mutation on demand. Cells have no mechanism for deliberately changing a base to gain a useful trait. Proofreading can undo an error, but nothing in a cell can decide to make a change. Mutations are accidents, not solutions.
This is the point where students slip into saying things like “the bacteria mutated so they could resist the antibiotic”. They did not. The mutation happened first, by chance, and the antibiotic then favoured the bacteria that already had it.
Worked examples
WORKED EXAMPLE
Re-grouping the triplets
A coding sequence reads ATG CCA GTC. Write the new triplets after (a) the fifth base is substituted for A, and (b) the fifth base is deleted.
Step 1: Write the sequence without gapsATGCCAGTC — the fifth base is C.
(a) Substitution: swap that C for an AATGCAAGTC → ATG CAA GTC
Only the middle triplet has changed.
(b) Deletion: remove that CATGCAGTC → ATG CAG TC
Every triplet from the second one onwards is different.
(a) one triplet altered (b) a frameshiftAlways rewrite the sequence with no gaps first, then re-group in threes from the left.
WORKED EXAMPLE
Naming the mutation type
The original sequence is GCT AAG CCA. Name the type of mutation in each case: (a) GCT AAG CGA, (b) GCT AAT GCC A, (c) GCT AGC CA.
(a) Count the bases
Still 9 bases; one letter differs → substitution(b) Count the bases
10 bases, one more than before → insertion (a frameshift)
(c) Count the bases
8 bases, one fewer → deletion (a frameshift)
(a) substitution (b) insertion (c) deletionCounting the bases is faster and safer than trying to spot the change by eye.
WORKED EXAMPLE
Comparing the damage
Explain why a deletion is usually more harmful to a protein than a substitution.
Step 1: What a substitution does
It changes only the triplet it lands in, so at most one amino acid is altered — and often none, because the code is degenerate.
Step 2: What a deletion does
Removing a base shifts every triplet after it, so the ribosome reads a completely different set of codons — a frameshift.
Step 3: Consequence for the protein
Every amino acid after the mutation may be wrong, and a premature stop codon may appear, so the polypeptide folds incorrectly or is cut short.
A deletion alters the whole sequence after the mutation, not just one tripletUse the word “frameshift” — it usually carries a mark of its own.
💡 Exam tip
Count the bases to identify the mutation type. Same number means substitution; one more means insertion; one fewer means deletion.
Use frameshift for insertions and deletions, and say what it does: every triplet after the mutation is re-grouped.
Name mutagens precisely: UV light, X-rays and gamma rays, chemicals in tobacco smoke. “Radiation” alone is vague.
Mention proofreading by DNA polymerase if asked why mutations are not more common than they are.
Say mutations occur at random. Never write that an organism mutated in order to gain an advantage.
Link mutation timing to S phase of interphase, when DNA is being replicated.
⚠ Common mix-up
Saying a substitution shifts the sequence. It does not — the base count is unchanged, so the triplets stay put.
Thinking mutations happen because they are needed. They are random accidents; selection acts afterwards.
Confusing mutagen with mutation. The mutagen is the cause; the mutation is the change.
Assuming every mutation changes the protein. Many land in non-coding DNA, and degeneracy absorbs many of the rest.
Mixing up gene mutation and chromosome mutation. This page is about changes to the base sequence, not whole chromosomes.
Forgetting that DNA polymerase proofreads. Replication is far more accurate than students usually assume.
Up next: Consequences of Mutations — now that you can name the three types, we look at what each one actually does to the finished protein, and why a mutation in a skin cell matters far less than the same mutation in an egg cell.
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