Mutations.

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The same meaning

A mutation is a change in the sequence of letters of the DNA. Mutations happen all the time: every time a cell copies its DNA a few mistakes slip past the repair systems, and radiation and some chemicals make more. Most mutations change nothing, some do harm, and a few help.

The simplest kind swaps one letter for another. What happens to the protein depends on the codon: it has “synonyms”, because most amino acids have more than one codon. Look inside stands at Folded protein, and when the protein changes, the original is drawn faded beside it. One-letter change is fixed at None until you choose an answer.

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A different amino acid

When the new codon stands for a different amino acid, the chain differs in one link: a missense mutation. Sometimes that hardly matters, and sometimes it changes everything. An amino acid that shuns water and sat inside the fold suddenly wants to face the water, and the chain folds differently.

The famous example is sickle-cell anaemia: one letter in the gene for haemoglobin, the protein that carries oxygen in red blood cells, turns GAG into GTG. One amino acid of $146$⁠ is swapped, and the haemoglobin molecules stick together into fibres that bend the cell out of shape.

Compare the new fold with the original one.

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An early stop

When the new codon is a stop codon, the ribosome releases the chain partway: a nonsense mutation. Everything that should have come after that point is never built.

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A lost letter

So far one letter has been swapped for another, and the number of letters stayed the same. What happens when a letter is lost, or an extra one is added?

The ribosome does not know where a “word” ends. It counts triplets from the AUG, so every letter lost or added shifts the reading frame of everything after it. One-letter change is fixed at None until you choose an answer.

Step 5 of 5

Three letters

Compare the protein after one letter is lost with the original: only the first three amino acids are left. Change One-letter change between the options, and compare the two folds each time.

And what if three letters are lost together, a whole codon? That is just what happens in the CFTR gene in most people with cystic fibrosis: three letters lost from a gene for about $1480$⁠ amino acids.