Effects of Frameshift Mutations: Definitions and Examples

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  • 0:06 Review of Mutation Types
  • 1:27 The Codon Reading Frame
  • 3:32 Frameshift Mutations
  • 6:17 A Real Frameshift Mutation
  • 7:00 Lesson Summary
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Lesson Transcript
Instructor: April Koch

April teaches high school science and holds a master's degree in education.

What is a frameshift in genetic translation? How can a frameshift mutation change a protein? In this lesson, learn about the codon reading frame and how frameshift mutations cause serious problems for polypeptide formation.

Review of Mutation Types

We already know that point mutations can cause changes to an organism. A mutation in DNA alters the mRNA code, which in turn can change what kind of protein is produced. Earlier we saw the effects of base substitutions. We used the example of the pink-winged pony to describe these effects. A missense mutation makes a slight change to a protein, a nonsense mutation blocks a protein's production, and a silent mutation does not affect the protein at all. These three different effects are all caused by base substitutions. They all result from the switching of one base for another.

If we look back at our chart on point mutations, we see that missense, nonsense, and silent mutations all happen because of base substitutions. But, base substitutions are only one kind of point mutation. We haven't yet discussed the effects of insertions and deletions. Insertions occur when one or more base pairs are added to the sequence, and deletions occur when base pairs are removed from the DNA sequence. Insertions and deletions actually change the length of the DNA strand because they add or subtract one base pair from the code. That's a big deal compared to base substitutions. Insertions and deletions can have drastic effects on the DNA code and the final protein. Let's dig deeper to learn more about the consequences of these disruptive mutation types.

The Codon Reading Frame

We'll first revisit the magikeratin gene that we used in our previous examples. It's an imaginary gene that codes for the magical keratin protein found in the feathers of the pink-winged pony. Below is the original DNA strand. The code is first transcribed into mRNA, and then it's translated into a chain of amino acids. The chain we normally get is methionine, proline, serine, and valine. That sequence makes up our magikeratin protein.

Image of magikeratin DNA

Now, what do you think would happen if we added one base to the strand of DNA? Would it change the length of the mRNA strand? Would it change the length of our amino acid chain? If so, then how much? Would we get one extra amino acid? Two more? Three more? What sort of effect would this have on the final product?

Let's think back to our codons for a minute. Whenever we translate an mRNA code, we read the letters in groups of three. We look at the long strand of bases, draw a few lines, and then hone in on one codon. We keep our focus on that codon while we check the RNA codon chart to find the matching amino acid. In that moment, we sort of have 'tunnel vision' for the codon in question. That 'tunnel vision' is actually called a reading frame. It's a way of dividing the mRNA into codons and focusing on one codon at a time.

A reading frame allows us to focus on one codon at a time.
Codon Reading Frame Example

The reading frame is something that we as humans use, but the concept is still the same for the molecules that are in charge of genetic translation. Inside our cells, ribosomes and tRNAs are working hard to match amino acids to every codon. They have their own sense of the reading frame, and they build polypeptides accordingly.

So, what would happen if we added a base? The DNA code would grow by one letter, and so would the mRNA code, giving us how many codons? Oh, weird! Below, look what happened to our reading frames! They all got shifted over by one. We still have five codons, but now there's one extra base. And the codons are all very different from the ones we had before. Our reading frames have shifted on the mRNA strand. This all happened because of a single base insertion. The effect that we get is called a frameshift.

Adding a base results in shift

Frameshift Mutations

A frameshift mutation is a mutation caused by an insertion or deletion, which causes a shift in the translational reading frame. Frameshift mutations have a more dramatic effect on the polypeptide than missense or nonsense mutations. Instead of just changing one amino acid, frameshifts cause a change in all the amino acids in the rest of the gene. Let's take our magikeratin gene for the pink-winged pony and see what results from a frameshift mutation.

Below is the original DNA strand. We'll make an insertion of an adenine base between the Gs. Also below is the resulting mRNA strand, and here's the resulting polypeptide: methionine, leucine, isoleucine, serine, and another leucine. Whoa. That's nothing at all like our magikeratin protein! I don't know what that is, but it's definitely not something that will give normal feathers to our pink-winged pony. If this kind of mutation happened, then the feather proteins would turn out very strange. The magikeratin would be incorrectly synthesized due to a serious defect in the amino acid chain. It'd be a safe bet that this pony couldn't fly at all.

Inserting an adenine base results in a different polypeptide.

So, we've tried an insertion. What about a deletion? Let's say we deleted the second G from the original DNA strand. Our resulting mRNA would give us the following polypeptide: methionine, histidine, glutamine, and phenylalanine. Once again, it's nothing like our magikeratin polypeptide. If this deletion happened to our pony, we'd get something just as bad as what we got from the insertion.

Frameshifts occurring early on have a much greater impact on the protein.
Frameshift Mutation Number Line

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