Mutations

Essential Question

How can a change in DNA change a protein and a trait?

A mutation is a change in the sequence of DNA. Some mutations change nothing, some harm the organism, and a few help. In this lesson you use the genetic code to predict how a change in a gene changes the protein it makes.

What Is a Mutation?

• A mutation is a change in the DNA sequence of a gene.
• Some mutations come from errors made when DNA is copied. Others are caused by environmental factors such as UV light, X-rays, and some chemicals.
• A mutation can have no effect, a harmful effect, or a helpful effect. The effect can depend on where the mutation is and on the environment.
• Only a mutation in an egg or sperm cell (a gamete) can be passed to offspring. Viable mutations that are inherited are a source of genetic variation.

Mutations add new versions of genes to a population, which is raw material for natural selection.

Substitutions

• A substitution replaces one base with another.
• A silent mutation changes the codon, but the new codon codes for the same amino acid.
• A missense mutation changes the codon so that it codes for a different amino acid.
• A nonsense mutation changes a codon into a stop codon, so the protein ends early.
• The diagram uses the first five codons of the example gene from this unit.

A substitution, often called a point mutation, changes at most one amino acid, or it shortens the protein if it creates a stop codon.

Insertions and Deletions

• An insertion adds one or more bases. A deletion removes one or more bases.
• If the number of bases added or removed is not a multiple of 3, the reading frame shifts. This is a frameshift mutation.
• A frameshift changes every codon after the mutation, so the amino acids after that point can all be different. A stop codon may appear early.
• Adding or removing a multiple of 3 bases keeps the frame, but it adds or removes whole amino acids.

A frameshift usually does much more damage than a substitution, because it changes every codon after it.

From DNA Change to Trait

• A gene change can change a protein. A protein change can change a trait.
• Sickle cell disease is an example. In the HBB gene, which codes for the beta-globin part of hemoglobin, one base is substituted. The DNA codon GAG becomes GTG, so the mRNA codon GAG (Glu) becomes GUG (Val).
• Hemoglobin with Val can clump together when it is not carrying oxygen, which changes the shape of red blood cells.
• The diagram shows a short stretch of the mRNA, simplified.
• A mutation is not harmful or helpful by itself. Its effect depends on the protein and on the environment.

A single-base substitution changed one amino acid, which changed the protein’s behavior and a trait of the organism.

↑ Back to top

---

Worked Examples

Try each problem on your own first, then open the solution to check your work.

Example 1: Classify the Mutation

The original mRNA is AUG GCU GAG UUU AAA CGU UGG UAA. Mutant 1 has AUG GCU GAA UUU AAA CGU UGG UAA, Mutant 2 has AUG GCU GUG UUU AAA CGU UGG UAA, and Mutant 3 has AUG GCU GAG UUU UAA CGU UGG UAA. Use the genetic code chart to classify each mutation as silent, missense, or nonsense.

Show the solution

1. Compare each mutant with the original to find the changed codon.
2. Mutant 1: GAG → GAA. GAG codes for Glu and GAA codes for Glu. Silent.
3. Mutant 2: GAG → GUG. GAG codes for Glu and GUG codes for Val. Missense.
4. Mutant 3: AAA → UAA. AAA codes for Lys and UAA is a stop codon. Nonsense. The protein ends after Met-Ala-Glu-Phe.
5. Answer: Mutant 1: silent. Mutant 2: missense. Mutant 3: nonsense.

Example 2: Insertion and Deletion

The original mRNA is AUG GCU GAG UUU AAA CGU UGG UAA, which gives Met-Ala-Glu-Phe-Lys-Arg-Trp. Translate each mutant and compare it with the original. (a) A U is inserted after AUG. (b) The C in the second codon (GCU) is deleted.

Show the solution

1. (a) New mRNA: AUGUGCUGAGUUUAAACGUUGGUAA. Regroup into codons: AUG UGC UGA GUU UAA ACG UUG GUA.
2. Translate: Met-Cys-Stop. The protein has only 2 amino acids instead of 7.
3. (b) New mRNA: AUGGUGAGUUUAAACGUUGGUAA. Regroup into codons: AUG GUG AGU UUA AAC GUU GGU, plus the leftover bases AA.
4. Translate: Met-Val-Ser-Leu-Asn-Val-Gly. Every amino acid after Met is different, and the original stop codon is no longer in the frame, so the ribosome would keep reading past this piece of mRNA.
5. Both are frameshift mutations, since 1 base was added or removed.
6. Answer: (a) Met-Cys-Stop. (b) Met-Val-Ser-Leu-Asn-Val-Gly with no stop codon in this piece. Both are frameshifts.

Example 3: Which Changes Hurt the Protein?

A scientist made four variants of a gene for an enzyme and measured the protein that each one makes (sample values for practice). Write a Claim, Evidence, Reasoning response about which types of mutations stop the enzyme from working.

Variant	Type of DNA change	Amino acids in protein	Enzyme activity (% of normal)
Normal	none	7	100
Variant A	silent	7	100
Variant B	missense	7	40
Variant C	nonsense	4	0
Variant D	insertion	2	0

Show the solution

1. Claim: A nonsense mutation and a frameshift mutation (an insertion) stop the enzyme from working, while a silent mutation does not, and a missense mutation reduces the activity.
2. Evidence: The silent variant (A) has 100% activity and the same 7 amino acids. The missense variant (B) still has 7 amino acids but only 40% activity. The nonsense variant (C) makes a protein of 4 amino acids with 0% activity. The insertion variant (D) makes a protein of 2 amino acids with 0% activity.
3. Reasoning: A silent change keeps the same amino acids, so the protein is the same. A missense change swaps one amino acid, which can change the shape a little, so some activity remains. A nonsense change or a frameshift shortens or scrambles the protein, so it cannot fold into a working enzyme.
4. Answer: Nonsense and frameshift mutations destroy the enzyme’s activity. Silent mutations do not, and missense mutations can reduce it.

↑ Back to top

---

Practice

Use the practice worksheet to classify mutations with the genetic code chart, compare substitutions with frameshifts, and use data to decide how a mutation changes a protein.

• Mutations Practice Worksheet (PDF)
• Mutations Practice Answer Key (PDF)

↑ Back to top

---

Lesson Slides

• 9.7 Mutations Slides (PDF)

↑ Back to top

---

Big Ideas

• A mutation is a change in the DNA sequence. It can come from copying errors or from environmental factors.
• Substitutions can be silent, missense, or nonsense.
• Insertions and deletions of a number of bases that is not a multiple of 3 cause a frameshift.
• A change in a gene can change a protein, and a change in a protein can change a trait.
• Only mutations in gametes can be inherited. Inherited mutations add genetic variation to a population.

Back to the essential question: A change in DNA changes the codons of an mRNA, which can change the amino acids of a protein. A silent mutation changes nothing, a missense mutation changes one amino acid, and a nonsense mutation or frameshift can destroy the protein. A changed protein can change a trait.

↑ Back to top

---

↑ Back to top