Mutations and Their Effect on Proteins
Explain how a DNA mutation can affect an amino acid sequence, protein folding and enzyme activity. Compare substitutions with reading-frame shifts and explain why some mutations have no visible effect.
What a learner can do afterwards
- Uses a supplied mRNA codon table to work out the amino acid effect of a single-base substitution.
- Explains how an amino acid change can affect an enzyme's active site, and why changes elsewhere can also affect function.
- Gives a reason why a mutation may have no visible effect.
1 · Read
You have traced DNA instructions into a protein. A mutation changes the DNA sequence. A substitution replaces one base. Within a protein-coding sequence, it can leave an amino acid unchanged, replace it with another, or create a stop codon. The DNA change affects the mRNA copy. We read mRNA codons using U rather than DNA's T.
Codons are read in threes from the start codon. Adding or deleting one base within the coding sequence shifts later triplet boundaries. This frameshift can change later amino acids or introduce an early stop. Adding or deleting a multiple of three bases preserves the downstream frame. Deleting a whole amino-acid codon removes one amino acid, which can still affect protein function.
Use this mRNA table: CAA and CAG encode glutamine; UUU and UUC encode phenylalanine; UAU encodes tyrosine; UAA means stop. UUU to UUC keeps phenylalanine, a silent substitution. UUU to UAU replaces it with tyrosine. UAU to UAA creates a stop. An early stop shortens the chain and may prevent it from working.
An enzyme binds its substrate at an active site and helps a reaction happen. An amino acid replacement can alter folding or active-site shape without changing chain length. Changes elsewhere can also affect activity. An early stop shortens the chain. Use test results to compare effects: reduced binding differs from complete loss of binding, and unchanged activity in one test does not establish unchanged function in other conditions.
A mutation may have no visible effect because it keeps the amino acid sequence, affects DNA with no relevant role in the conditions being studied, or changes a protein without disrupting its job. Noncoding DNA can also control gene activity, so noncoding does not mean unimportant. A mutation's effect can be neutral, harmful or helpful, depending on what changes and the environment.
Many DNA polymerases proofread while copying DNA. Other repair enzymes can correct mismatches left afterward. These checks correct many copying errors before they persist as mutations. UV light and some chemicals in tobacco smoke can damage DNA and increase mutation risk. DNA damage does not always become a mutation.
Trace DNA to mRNA to amino acids, then consider folding and activity. Some changes have no visible effect; others affect function. Location alone does not settle the outcome.
Lesson revisions, questions and flashcards written for this dataset. OpenStax mutation, repair and replication records were consulted for scientific facts.
Readings and flashcards written for this dataset, with OpenStax records consulted for facts. Video reference: Khan Academy on YouTube.
More to read
Compare the sequence before predicting the effect
Locate the changed bases before deciding what a mutation might do. Within a protein-coding sequence, a substitution can change a codon's meaning or leave its amino acid unchanged. Count inserted or deleted bases too. Losing one base moves later triplet boundaries. Losing a whole amino-acid codon keeps those later boundaries but removes an amino acid. These are different sequence effects. Neither tells you the complete effect on the organism. The resulting protein might still work, work less well or lose its activity. Measurements can help distinguish those possibilities.
Damage, repair and lasting changes
DNA damage need not become a lasting sequence change. For example, UV light can join neighbouring thymine bases and distort the DNA. Repair enzymes can remove a damaged stretch and rebuild it using the other strand as a guide. Copying errors have checks too. Many DNA polymerases can remove an incorrectly added base during copying, and mismatch repair can correct errors left afterward. These processes reduce the number of changes that persist. They do not repair every problem. A defect in a repair system can allow more mutations to accumulate.
Why a template helps preserve DNA
Each DNA strand can guide the building of a partner strand. A pairs with T, and C pairs with G. An incorrectly paired base gives the copying and repair machinery a mismatch to check. If the mismatch is corrected, the original sequence can be preserved. If it escapes correction, later copying can establish the changed sequence in a DNA molecule. This separates a copying mistake from a mutation that persists. Error rates vary with the enzyme, the cell and its repair systems, so one numerical rate should not be applied to every case.
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2 · Watch
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Where it sits
8 questions wait behind this lesson, each with its answer explained. Every answer feeds the sky: stars light as they are learned, and dim when it is time to come back.