Types of genetic mutations

TL;DR:

• A point mutation changes one base. It can be silent (same amino acid), missense (different amino acid) or nonsense (a stop codon).

• An insertion or deletion that is not a multiple of three bases shifts the reading frame and changes every codon after it.

• To find the effect, rewrite the mRNA, split it into codons, and translate both versions.

A mutation is a change in the DNA sequence. Some changes do nothing, some swap one amino acid, and some wreck the whole protein. The way to tell them apart is to run the same translation twice, once on the original and once on the mutant, and compare. That is the whole method of this article.

The idea in plain words

A point mutation replaces one base with another. An insertion adds one or more bases, and a deletion removes them. Mutations arise from copying errors and from damage by chemicals or radiation, and they matter only if they change the protein or how much of it is made. If you need a refresher on reading codons, see from DNA to protein.

Why the type depends on the code

The genetic code reads three bases at a time, and several codons name the same amino acid. So a one-base change can leave the amino acid alone, change it, or turn it into a stop. An insertion or deletion is different: it moves the boundaries between codons for everything downstream.

Worked example: one gene, four edits

Take this short mRNA, split into codons, and translate it.

Original: AUG CAU GGC AAA UGA
Protein : Met-His-Gly-Lys-(stop)

Codon table entries used here: AUG Met, CAU His, CAA Gln, GGC and GGA Gly, AAA Lys, GCA Ala, UGG Trp, and UAA, UGA stop. Now apply four edits, each to the original.

1. Silent substitution. Change the third base of GGC from C to A: GGC → GGA. Both code for glycine. The protein is still Met-His-Gly-Lys.

2. Missense substitution. Change the last base of CAU from U to A: CAU → CAA. Histidine becomes glutamine. The protein is Met-Gln-Gly-Lys: one amino acid is different.

3. Nonsense substitution. Change the first base of AAA from A to U: AAA → UAA, a stop codon. Translation ends early. The protein is Met-His-Gly, three amino acids instead of four.

4. Frameshift by insertion. Insert one G after AUG. The 16 bases AUGGCAUGGCAAAUGA now split as AUG GCA UGG CAA AUG A. The protein becomes Met-Ala-Trp-Gln-Met, and the old stop codon UGA is no longer in frame.

Notice the size of the effect. The silent change leaves everything intact. The missense one changes a single amino acid, which may or may not matter. The nonsense mutation loses the end of the protein. The frameshift alters all four amino acids after the start.

A real case: sickle cell

In the gene for one part of haemoglobin, the codon GAG, which codes for glutamic acid, becomes GUG in the mRNA, which codes for valine. That is a missense mutation from a single base change. The result is a haemoglobin that can clump and distort red blood cells. One changed amino acid in a chain of 146 is enough to alter how the protein behaves.

Why insertions of three are different

Try one more edit on the same mRNA. Insert three bases, GGG, right after the first AUG. The codons become AUG GGG CAU GGC AAA UGA, which is Met-Gly-His-Gly-Lys. One amino acid was added and the rest of the protein is intact, because the frame is preserved.

So the rule is about the number of bases, not the number of edits. Adding or removing a multiple of three keeps the frame, while one or two bases shifts it. An insertion of three bases inside a codon would alter that one codon, but not the ones after it.

How to check your answer

• Write the original and the mutant side by side, with codon boundaries marked.

• Count the bases. If you inserted or deleted one or two, the codons after that point must shift. If you inserted three, the frame holds.

• For a substitution, only one codon should differ. If several differ, you made a frameshift or a slip.

• Look for stop codons in the mutant, in frame.

Common mistakes

• Saying every mutation is harmful. Many are silent or have little effect, and a few are useful.

• Calling a one-base change a frameshift. Substitutions do not shift the frame.

• Forgetting that the stop codon at the end of the gene can be lost or moved.

• Counting a stop codon as an amino acid.

Where you will use it next

Mutations are the source of new alleles, which natural selection then sorts: see how natural selection works. They also link to genetic testing, cancer biology and evolution. Questions about your own genetic health belong with a doctor or genetic counsellor.

Frequently asked questions

Can a mutation happen outside a gene?

Yes. Many DNA changes fall in regions that do not code for protein, and they often have no visible effect.

Do all mutations get passed on?

Only those in cells that make eggs or sperm can be inherited. A change in a skin cell is not passed to children.