Are STOP codons impacted by base insertion or deletion mutation?

Question

I am learning about base insertion and deletion mutations. An example in my textbook is given below.

GUU CCA CAU AUC.

So if there is an insertion (of guanine):

GUU GCC ACA UAU C_ _ (there will be a detrimental effect on the protein created).

I'm a bit confused about how the stop codon will be read. If we have a new example with a stop codon:

GUU CCA CAU AUC UAG

When the mutation occurs (insertion of guanine) will it become:

1) GUU GCC ACA UAU CUA G

OR

2) GUU GCC ACA UAU C_ _ UAG

If mutation 1) occurs, there would be no stop codon, but mutation 2) looks strange to me. So which is the right one?

Thanks

Answer 1

Yes. Mutations can affect STOP codons and they do relatively commonly. These are important because they can lead to significant changes in the resulting peptide and are likely to affect protein functions or phenotype.

For a point mutation (a single base substitution), there are several possible effects:

• silent mutation is a synonymous base substitution which does not change the encoded amino acids (this is neutral variation).

• missense mutation is a non-synonymous bass substitution which changes only one amino acid in the protein (these can affect protein functions but do not always).

• nonsense mutation is a change in a coding codon to a STOP codon (this truncates the encoded amino acid sequence prematurely resulting in a shorter peptide).

• nonstop mutation is a change from a STOP codon to a coding codon (this means the amino acid sequence will continue to the next STOP codon resulting in a longer peptide).

Insertions and Deletions in DNA sequence (InDels) are important because they change all codons that follow it (not just the base substituted):

• frameshift mutation adds or removes a base which resulting in a change in the reading frame: all bases following will result in new codons, including STOP codons (this commonly results in entirely new protein domains and proteins of different lengths as STOP codons will also be changed. They are encoded in the reading frame like all other codons.

As you can see, mutations which affect STOP codons are very important as they drastically change the protein sequence. This usually disrupts the protein function and causes diseases or inviable embryos. Most of these are removed from populations long-term by natural selection. However, it can rarely lead to entirely new proteins beneficial to the organism and evolutionary changes. This is more likely with duplicated genes where one can change while the other retains the original function.

As such, mutations involving STOP codons are among the most biologically important. Another important case is splice functions. Point mutations and frameshifts can also affect intron-exon boundaries, resulting in new splice variants, skipped exons, and reading further into introns (which may contain splice junctions or STOP codons).

Answer 2

Let's start with your example:

Wild-type gene looks like:

GUU CCA CAU AUC UAG*

After G insertion, you end up with

GUU GCC ACA UAU CUA G

There are 3 stop codons: UAG*, UAA*, UGA*

You don't see those in your mutated gene, because you truncated sequence. Let's imagine that gene actually goes like this:

WT: GUU CCA CAU AUC UAG* GCG UCU AAA ACG CUA

Mut: GUU GCC ACA UAU CUA GGC GUC UAA* AAC GCU A...

In mutant you got now new stop codon created

Gene, transcribed into mRNA doesn't stop at stop codon, there is whole bunch of sequence after it too (3'-UTR and poly-A tail for Eukaryotas)