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Mutations are changes in a cell’s DNA sequence. When a mutation happens in the coding sequence of a gene, the resulting protein is changed. In this lesson, discover what a nonsense mutation is and what effects it has on the protein that is made from a gene.

Nonsense Mutation Definition

When you think about a mutant, you might think about sci-fi movies where mutated creatures become powerful and evil and then attempt to destroy the world.

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But what are mutations, really? Mutations are changes to a cell’s DNA sequence, and there are several different types.A nonsense mutation is a point mutation that introduces a premature stop codon into the part of the gene that encodes a protein. A stop codon is like a period at the end of a sentence. It instructs the ribosome to stop making the protein. So, if a mutation leads to an early stop codon, only part of the protein will be made.

Half-baked proteins that result from nonsense mutations are often nonfunctional or defective. Now let’s learn more about how nonsense mutations work and their consequences.

Genetic Code Review

The DNA sequence of the coding region of a gene is transcribed into a messenger RNA molecule, whose sequence is in turn read and decoded by the ribosome and transfers RNAs during translation.The sequence of a messenger RNA is read in groups of three nucleotides called codons.

Each possible combination of the three RNA nucleotides (A, G, C and U) codes for an amino acid, translation start or translation stop. What you’re looking at on screen is a table that shows what each codon means to the ribosome and transfer RNAs.

This table shows all of the possible codons and their meanings.
A diagram showing different types of point mutations.</p>
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<p>Under ‘No mutation,’ you can see that the normal DNA sequence at this locus is TTC, which is transcribed to the sequence AAG in the messenger RNA. AAG normally codes for the amino acid lysine at the protein level.Now let’s imagine that the cell undergoes some radiation or other DNA damage and a point mutation occurs that changes the TTC to ATC. This is a nonsense mutation, and here’s why: now, the DNA sequence will be transcribed to UAG in the messenger RNA. UAG is a stop codon, which tells the ribosome to stop translating and let the protein go out into the world of the cell to begin doing its job.</p>
<p><h2>Consequences of Nonsense Mutations</h2>
<p>So, instead of getting a lysine amino acid and then the rest of the remaining amino acids in the sequence, this protein will be unfinished. A shortened, truncated version of the protein will be made and released to do its job in the cell.But is this truncated protein actually capable of doing its job? Probably not. It depends how close the nonsense mutation occurred to the real end of the messenger RNA sequence.</p>
<p> Maybe the protein was almost finished anyway, so it could retain most of its functionality.However, very often, nonsense mutations yield nonfunctional proteins. Because they are only partially made, they don’t fold correctly and can’t perform their roles in a cell.</p>
<p>There are many examples of nonsense mutations that lead to human disease. Here’s one: if a nonsense mutation occurs in the gene that encodes the CFTR protein, it can lead to cystic fibrosis. There are many known mutations that yield a nonfunctional CFTR protein and cystic fibrosis, and nonsense mutations are one type.</p>
<h2>Lesson Summary</h2>
<p>In this lesson, we quickly recapped the <b>central dogma</b> of molecular biology, which states that genetic sequence information flows from DNA to RNA to protein in a cell.</p>
<p> Then we learned that a <b>nonsense mutation</b> is a type of point mutation that introduces a premature stop codon into the coding region of a gene and that <b>stop codons</b> instruct the ribosome to stop making the protein, while also learning that a <b>codon</b> is a group of three nucleotides. We also learned about the different <b>point mutations</b>, which are changes in one nucleotide base pair of a cell’s DNA sequence: missense mutations, nonsense mutations, silent mutations, and readthrough mutations. However, we focused more of our attention on learning about nonsense mutations, particular type of point mutation that can lead to shortened, truncated proteins that are often nonfunctional because they can’t fold correctly.</p>
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