A changed base is only the beginning of the story. What happens next depends on which triplet it hits, whether the reading frame survives, and — crucially — which type of cell it happened in. The same mutation can be completely harmless in one cell and passed to every descendant in another.
📘 What you need to know
A substitution can be silent (no change to the amino acid), missense (one amino acid swapped) or nonsense (a premature stop codon).
Substitutions produce single nucleotide polymorphisms (SNPs), which occur roughly once in every 300 nucleotides — about 10 million in the human genome.
SNPs are commonly found in non-coding regions and can act as biological markers for locating disease-associated genes.
Insertions and deletions cause a frameshift, changing every codon after the mutation. They are usually far more damaging than substitutions.
Frameshifts during translation are rare (about 10−5 to 10−7 per codon) but the effects are usually catastrophic.
Germ cell mutations are passed to offspring; somatic cell mutations are not, and are associated with cancer.
A mutated gene that causes cancer is called an oncogene. Cancers arise from uncontrolled mitosis forming a tumour.
Three outcomes of a substitution
You met these on Protein Structure & Mutations; here is the detail HL expects. Because the genetic code is degenerate, swapping a base does not automatically swap an amino acid.
Silent mutations are common and invisible. Nonsense mutations are rarer and usually severe, because a truncated chain cannot fold into a working protein.
Why nonsense is the worst of the three. A premature stop codon ends translation early, so the polypeptide is incomplete. It is missing whole sections needed for folding, so the final structure — and therefore the function — is lost, not just altered.
SNPs: the substitutions we all carry
A base substitution that is common in a population is called a single nucleotide polymorphism, or SNP (said “snip”). A SNP is simply a difference at one nucleotide position — for example, one person has a C where another has a T in the same stretch of DNA.
SNPs occur normally throughout everyone’s DNA, roughly once every 300 nucleotides.
That works out at about 10 million SNPs in a human genome.
Most sit in non-coding regions between genes, so they have no direct effect on any protein.
They are extremely useful as biological markers: if a particular SNP is regularly inherited alongside a disease, it helps researchers locate the gene responsible.
A SNP is not automatically a problem. Most of the “genetic differences” between you and the person sitting next to you are SNPs, and almost none of them do anything at all. They are markers, like signposts on a road — useful for finding your way, not for driving the car.
What a frameshift does
Insertions and deletions are usually far more harmful than substitutions, because of the way the ribosome reads mRNA. It reads in codons of three, from a fixed starting point, and it has no way of knowing that a base has been added or removed. It simply carries on reading in threes.
The result is that every codon after the mutation is different. The wrong amino acids are added, and often a stop codon appears by accident, cutting the chain short. The protein produced bears almost no resemblance to the intended one.
Compare the two rows of amino acids. A single missing base has rewritten the entire polypeptide from that point on.
Which cell it happened in changes everything
The same mutation can be trivial or life-changing depending on the cell type it occurs in.
Feature
Germ cells
Somatic cells
What they produce
Gametes, by meiosis
Body cells, by mitosis
Inherited?
Yes — passed to offspring and later generations
No — lost when the affected cells die
Reach within an organism
Every cell of any offspring formed from that gamete
Only the affected cell and its descendants
Main significance
Genetic disease and evolution
Cancers
Germ cells
Eggs, sperm and the zygote are together known as the germ line. A mutation in a sperm cell can affect the zygote it forms, and because that zygote divides to make the whole organism, every cell of the offspring will carry it. A female who has inherited a mutation carries it in the germ cells of her ovaries, so it can be passed on again.
Somatic cells and cancer
Somatic mutations are not inherited, but they are the origin of cancers. Cancers arise when a mutation occurs in a gene that controls cell division. The cell then divides repeatedly and uncontrollably by mitosis, producing an irregular mass of cells called a tumour. A mutated gene that causes cancer is called an oncogene.
Mutations are common and most do not lead to cancer. Usually the affected cell either dies early or is destroyed by the immune system, and because most cells are easily replaced this causes no harm. Cancerous cells are the ones that escape both of those fates.
Notice how much has to go right for a cancer to form: the mutation must hit a cell-cycle gene, avoid proofreading, avoid early cell death, and avoid the immune system. That is why cancer risk rises with age — more divisions mean more chances for all four to line up.
Worked examples
WORKED EXAMPLE
Reading a frameshift
An mRNA sequence reads ACG UUC GAU CAA. The first base is deleted. Use a codon table to deduce the new amino acid sequence and comment on the effect.
Step 1: Rewrite without the deleted baseCGUUCGAUCAAStep 2: Re-group into codons from the leftCGU UCG AUC AAStep 3: Look them upCGU = Arg UCG = Ser AUC = Ile
Original: Thr – Phe – Asp – Gln
New sequence Arg – Ser – Ile: no amino acid in commonThe final two bases are left over, so the reading frame runs off the end of the sequence given.
WORKED EXAMPLE
Estimating the number of SNPs
The human genome contains about 3 000 000 000 nucleotides, and a SNP occurs on average once in every 300 nucleotides. Estimate the number of SNPs in a human genome.
Step 1: Set up the calculation
Number of SNPs = total nucleotides ÷ nucleotides per SNP
Step 2: Substitute3 000 000 000 ÷ 300 = 10 000 000About 10 million SNPsEstimation questions like this want the working shown, even when the numbers are round.
WORKED EXAMPLE
Which mutation is inherited?
A woman develops a mutation in a skin cell after sunbathing, and also carries a mutation in the cells of her ovaries. State which could be passed to her children and explain why.
Step 1: Classify each cell
Skin cell = somatic. Ovary cell = germ cell.
Step 2: Apply the rule
Only germ cells produce gametes, and only gametes pass DNA to the next generation.
Step 3: Say what happens to the other one
The skin cell mutation is lost when those cells die, though it could contribute to skin cancer.
Only the ovary (germ cell) mutation can be inheritedWatch for the word “gamete” or “ovary” in the question — it is the clue.
💡 Exam tip
Name the three substitution outcomes and give one consequence each: silent (no change), missense (one amino acid), nonsense (chain cut short).
Quote the SNP figures if you can: 1 in 300 nucleotides, about 10 million per genome.
When explaining a frameshift, say why it happens: the ribosome keeps reading in codons of three from a fixed point.
Use the words germ line and somatic rather than “sex cells” and “normal cells”.
For cancer, build the chain: mutation in a cell-division gene → uncontrolled mitosis → tumour. Name the oncogene.
Remember that most somatic mutations are removed by early cell death or the immune system.
⚠ Common mix-up
Saying a silent mutation does not change the DNA. It does — it just does not change the amino acid, because the code is degenerate.
Thinking every SNP causes disease. Most are in non-coding DNA and have no effect at all.
Saying frameshifts change “some” of the protein. They change everything after the mutation point.
Claiming somatic mutations are harmless. They are not inherited, but they can cause cancer.
Using oncogene for any mutated gene. It specifically means one that causes cancer.
Confusing a tumour with cancer spreading. A tumour is the mass of cells produced by uncontrolled mitosis.
Up next: Mutations & Genetic Variation — so far mutations have looked like bad news. Now for the other side: without them there would be no new alleles at all, and no evolution.
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