A mutation, which geneticists now usually call a gene variant, is a permanent change in the DNA sequence. Grade 9 and 10 biology, AP Biology and A-level all ask for the types and for an example of each effect: harmful, beneficial, neutral. The definitions below are MedlinePlus Genetics' (the US National Library of Medicine), the examples come from its condition pages, and the chart is on the printable.
Download the types of mutations chart (PDF) (the types with what each does to the protein on page 1, the harmful, beneficial and neutral examples, germline against somatic and a practice set with answers on page 2; two pages, free).
The types of mutation
DNA is read three bases at a time; each triplet (codon) names one amino acid or says stop. Every type below is a change to that letter sequence.
| Type | What changes | Effect on the protein |
|---|---|---|
| Substitution | one nucleotide replaced by another | depends on the new codon: missense swaps one amino acid for another and "may alter the function of the protein"; nonsense creates "a stop signal that prematurely signals the cell to stop building a protein"; a silent substitution names the same amino acid and changes nothing |
| Insertion | one or more nucleotides added | if not a multiple of three, a frameshift; otherwise extra amino acids |
| Deletion | at least one nucleotide removed; large deletions can remove a whole gene or several neighbouring genes | if not a multiple of three, a frameshift; otherwise missing amino acids |
| Deletion-insertion (indel) | a deletion and an insertion at the same spot, complex enough to differ from a simple substitution | as above, by the net change |
| Duplication | a stretch of nucleotides copied and repeated next to the original | extra sequence; a frameshift if the length is not a multiple of three |
| Inversion | a stretch of more than one nucleotide replaced by the same sequence in reverse order | the codons inside are scrambled |
| Frameshift | the result of an insertion, deletion or duplication that shifts the reading frame | "the code for all downstream amino acids" changes; usually a non-working protein |
| Repeat expansion | the number of copies of a short repeated sequence (three or four nucleotides) increases | a longer protein or disrupted gene; the mechanism behind several inherited neurological conditions |
A worked frameshift, with the sentence THE CAT ATE THE RAT read three letters at a time: delete the first T and it becomes HEC ATA TET HER AT. Every word after the change is wrong, which is what a frameshift does to amino acids.
Harmful, beneficial, neutral: it depends where the change is
MedlinePlus puts it in one line: variants have "varying effects on health," depending on where they occur and whether they alter the function of essential proteins. Three examples, one of each.
Harmful: sickle cell disease. "One particular HBB gene variant produces an abnormal version of beta-globin known as hemoglobin S." Beta-globin is part of hemoglobin, the oxygen carrier in red blood cells; with hemoglobin S the cells can bend into a sickle shape, block small vessels and break down early. The condition is autosomal recessive (both copies of the gene must carry a variant; carriers with one copy usually have no symptoms). It affects an estimated 100,000 Americans, about 1 in 500 African Americans and 1 in 1,000 to 1,400 Hispanic Americans, and millions of people worldwide, most commonly those whose ancestors came from Africa, the Mediterranean, the Arabian Peninsula, India and some Spanish-speaking regions.
Beneficial: lactase persistence. Lactase is the enzyme that digests lactose, the sugar in milk. In most mammals, and in about 65 percent of people, lactase production falls after infancy (lactase nonpersistence). The LCT gene that makes lactase is controlled by a regulatory element inside the neighbouring MCM6 gene, and some people inherit changes in that element that lead to sustained lactase production in the small intestine; this persistence is autosomal dominant, one copy is enough. Nonpersistence is most prevalent in people of East Asian descent (70 to 100 percent), very common in people of West African, Arab, Jewish, Greek and Italian descent, and found in only about 5 percent of people of Northern European descent, whose ancestors kept dairy animals. A single regulatory variant, and a population can live on milk.
Neutral: the great majority. A silent substitution that names the same amino acid, a change in the long stretches of DNA between genes, a missense change that swaps one amino acid for a similar one in a part of the protein that does not matter: these alter nothing a person can notice. Most of the variants that make one person's genome differ from another's are of this kind.
Germline and somatic
- Germline: the variant is in an egg or a sperm, so every cell of the child carries it and it can be passed on. Sickle cell disease and lactase persistence are germline.
- Somatic: the variant arises in one body cell after conception (skin cells in sunlight, lung cells in smoke, any cell when DNA is copied imperfectly). Only that cell's descendants carry it; it is not inherited. Most cancers begin with somatic variants that let a cell divide without control.
What causes mutations
Copying errors when DNA is replicated before a cell divides (the cell's proofreading catches most but not all); radiation (ultraviolet light, X-rays); chemicals that react with DNA (in tobacco smoke, for instance); some viruses. Variants that arise with no outside cause are called spontaneous. A mutagen is anything that raises the rate.
Worked questions
- GCA becomes GCG. Both code for alanine. A silent substitution: neutral.
- CAG (glutamine) becomes TAG (stop). A nonsense substitution: the protein is cut short.
- Two bases are inserted into a coding sequence. Two is not a multiple of three: a frameshift.
- Three bases are deleted. The frame holds; one amino acid is missing; the effect depends on which one.
- A variant in a sperm cell. Germline: can be inherited.
- A sunburnt skin cell's DNA changes. Somatic: not inherited.
The mistakes that lose marks
- "All mutations are harmful": most are neutral, some are beneficial, and the examiner wants an example of each.
- Calling every substitution a frameshift: a substitution keeps the frame; only insertions and deletions not divisible by three shift it.
- Confusing missense (wrong amino acid) with nonsense (stop).
- Saying sickle cell disease is caused by "a mutation in hemoglobin": the variant is in the HBB gene, which makes the beta-globin part of hemoglobin.
- Writing that somatic variants are inherited.
Where to get help
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Related pages
- Artificial selection: how selective breeding works
- Adaptations in animals and plants
- Monomers and polymers of the four macromolecules
Questions parents ask
1What are the types of mutations?
2What is the difference between a missense and a nonsense mutation?
3What is a frameshift mutation?
4Are all mutations harmful?
5What is the difference between a germline and a somatic mutation?
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