What is frameshift mutation?

What is frameshift mutation?

A frameshift mutation occurs when nucleotides are inserted into or deleted from the DNA and cause a shift in the reading of mRNA codons.Frameshift mutations are insertions or deletions of nucleotides in DNA that change the reading frame (the grouping of codons).
Recall that a codon is a group of 3 nucleotides that corresponds with a specific amino acid.
We can demonstrate a frameshift mutation using this example:
Say we have a letter sequence of
THE FAT CAT SAT
If one letter (similar to one nucleotide), like an extra E, is inserted into this sequence, we would get
TH$color(red)(E)$ EFA TCA TSA T
Just by inserting one extra E, the entire reading of the sentence changed. Note how it caused a shift in the pattern, and affected every single letter after it. Now the words are just gibberish.
Similarly, if this was the code for a protein, the ribosomes would have a difficult time translating this sequence correctly.
What if the F was deleted from the sequence?
THE ATC ATS AT
Like the insertion, a deletion can also cause a shift in the pattern and affect all subsequent letters.

It is important to note that frameshifts only occur if the insertion or deletion of nucleotides is not a multiple of 3. Since codons are read in groups of 3, an insertion of 3 or 6 would not cause a shift in the positions of all subsequent nucleotides.
If a frameshift mutation occurs, then the mRNA codons will code for different amino acids. Since amino acids make up proteins, the resulting protein will not function properly (or not function at all).
A mutation that occurs early in the sequence could have more adverse effects, since it affects more nucleotides down the line.
It is also possible that the mutated code contains an early stop codon (UAA, UAG, or UGA) and stops translation early, resulting in an abnormally short polypeptide.

What is frameshift mutation?

Biological Definition:

When nucleotides are inserted or deleted from the DNA and cause a “shift” in the reading of mRNA codons, the procedure is known as frameshift mutation.

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

Explanation:

The reading frame of DNA is changed by insertions or deletions of nucleotides in DNA, we call the respective procedure as frameshift mutations.
Frameshift mutations have a more dramatic effect on the polypeptide than missense or nonsense mutations. In translation, the ribosome moves down the mRNA 3 bases at a time and reads whatever codons follow the start codon. Adding or subtracting one of two bases (or any other number that is not a multiple of 3) can disrupt the normal reading frame and lead to the production of a completely nonfunctional protein. Frame shifts may also accidentally introduce an early stop codon.

Example:

Let’s demonstrate the frameshift mutation with the help of an example.
If the F is deleted from the sequence given:

THE FAT CAT SAT

Since codon is a group of 3 nucleotides which corresponds with a specific amino acid. So after deletion the resultant sequence will become:

THE ATC ATS AT

Just by deleting one letter, the entire reading of the sentence changed.

Note:

  • How it caused a shift in the pattern, and affected every single letter after it. Now the words are just gibberish.

  • Similarly, if this was the code for a protein, the ribosomes would have a difficult time translating this sequence correctly.

Effect of frameshift mutation:

Frameshift mutations are among the most deleterious changes to the coding sequence of a protein.
They are extremely likely to lead to large-scale changes to polypeptide length and chemical composition, resulting in a non-functional protein that often disrupts the biochemical processes of a cell.
Deletion from the original DNA strand would result mRNA that contains methionine, histidine, glutamine, and phenylalanine.
Since protein-coding DNA is divided into codons three bases long, insertion and deletion both can alter a gene so that its message is no longer correctly parsed.