can a point mutation cause a frameshift? [closed]

Question

During translation initiation, a tRNA loaded with Methonine binds to the small ribosomal subunit. Subsequently, a mRNA molecule, recognized by the 5 cap, binds to the small subunit, and the tRNA scans the mRNA molecule for the presence of AUG which is the start codon. A point mutation could result in the the sequence AUG to be present after the ribosome binding site, but upstream of the "true" start codon.

Question 1:Will translation start at the mutated site?

Question 2: Could the mutation result in a frameshift, with a truncated protein as a consequence?

I have not found much information about this. I did find one homepage, with lecture notes from a genetics course at University of New Mexico referring to this type of mutation as a start-gain mutation.

http://www.discoveryandinnovation.com/BIOL202/notes/lecture14.html

"Start gain. A start-gain mutation is a point mutation creating a new ATG start codon upstream of the original start translation site. If the new ATG is close enough to the original one (so that it is within the processed transcript and downstream of a ribosome-binding site) and in frame, it will be used to initiate translation, adding amino acids to the amino terminus of the original protein. It is also possible for a start-gain mutation to be out of frame, which will not affect translation of the original protein. In general, start-gain mutations have a low impact on gene function."

I have not come across the term start-gain mutation before, but it sounds like what I am describing.

Question 3: If the start-gain mutation is out of frame, why will it not affect translation of the original protein?

Question 4: It is my understanding that the start codon sets the reading frame, and not the bases prior to the start codon. If the bases prior to the start codon are also "read" in triples, which position in the mRNA transcript sets the reading frame?

Thanks

Answer 1

I saw the OP edited it's question quite a lot.. This answer answers the questions before the edit, I will not delete this because it will maybe help other people
I'm not sure if you fully understand the terms you used so I will start with clarifying these.

Missense mutation

a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid (wiki)

Example

    DNA: 5' - AAC AGC CTG CGT ACG GCT CTC - 3'
         3' - TTG TCG GAC GCA TGC CGA GAG - 5'
   mRNA: 5' - AAC AGC CUG CGU ACG GCU CUC - 3'
Protein:      Asn Ser Leu Arg Thr Ala Leu

-------------------------↓↓↓↓↓↓↓--------------------------
    DNA: 5' - AAC AGC CTG CTT ACG GCT CTC - 3'
         3' - TTG TCG GAC GAA TGC CGA GAG - 5'
   mRNA: 5' - AAC AGC CUG CUU ACG GCU CUC - 3'
Protein:      Asn Ser Leu Leu Thr Ala Leu

The 4th codon which was CGT (and GCA on the other strand) is changed because of a subtitution of the G for a T. Because of this change the codon will not code for Arg anymore but instead it will code for Leu. So a missense mutation causes the sequence to be in the same frame as before however a codon is changed and subsequently an other amino acid is added to the polypeptide chain during translation (this is not always the case see wobble)

Frameshift mutation

A frameshift mutation (also called a framing error or a reading frame shift) is a genetic mutation caused by indels (insertions or deletions) of a number of nucleotides in a DNA sequence that is not divisible by three. (wiki) Example

    DNA: 5' - AAC AGC CTG CGT ACG GCT CTC - 3'
         3' - TTG TCG GAC GCA TGC CGA GAG - 5'
   mRNA: 5' - AAC AGC CUG CGU ACG GCU CUC - 3'
Protein:      Asn Ser Leu Arg Thr Ala Leu

-------------------------↓↓↓↓↓↓↓--------------------------
    DNA: 5' - AAC AGC CTG CTT ACG CT C    TC - 3'
         3' - TTG TCG GAC GAA TGC GA G    AG - 5'
   mRNA: 5' - AAC AGC CUG CUU ACG CU C    UC - 3'
Protein:      Asn Ser Leu Leu Thr Leu ..........

In this case the nucleotide T is removed and thus causing a framehift because we need tree bases to form a codon. by removing a nucleotide we just read further till we find a third base and this will be our "new" codon. This new codon does not code for Ala anymore but will code for Leu. (I added the dots because of the fact that the stop codon will/can be shifted and the transcript can be either shorter or longer (the previous stop codon will no longer exist).

---

Could a missense mutation cause a frameshift

In the case of a missense mutation the DNA sequence will be in the same frame (no nucleotide is added or removed) and in the case of a frameshift a nucleotide needs to be added or removed and therefore a missense can't cause a frameshift.

such that a mutation results in the sequence AUG?

Both a missense and a frameshift could result in a start codon.
Example (frameshift)

mRNA 5'     AAC AUU GAC 3'
Protein:    Asp Ile Asp
    -------------------------↓↓↓↓↓↓↓--------------------------
mRNA 5'     AAC AU G  AC.... 3'
Protein:    Asp Met   ........

Example (missense)

mRNA 5'     AAC AUU GAC 3'
Protein:    Asp Ile Asp
    -------------------------↓↓↓↓↓↓↓--------------------------
mRNA 5'     AAC AUG  GAC 3'
Protein:    Asp Met  Asp

So both a frameshift mutation and a missense mutation can introduce a Met --> a start codon.

a mutation results in the sequence AUG to be present in the transcript but upstream the start codon?

A gene is only transcribed if this gene is preceeded by the appropriate sequences:
The start codon will be present in the first exon so the only way to put a start codon before the "old" start codon while remaining all other sequences(UTR,promtor, enhancers etc.) in tact is to "create" one just behind the 5' UTR and before the "old" start codon in the first exon. This can be done by just inserting AUG in there, HOWEVER we are talking about point mutations:

A point mutation, or single base modification, is a type of mutation that causes a single nucleotide base substitution, insertion, or deletion of the genetic material, DNA or RNA

The start codon we are talking about is positioned AFTER the 5' UTR (as said above):

By inspecting the "general" 5'UTR sequence we can see that there are already "start codons" (not really start codons because they are not translated") present before the start codon. We could probably add one using a frameshift or a missense mutation as described above and in your edited question:

If the new ATG is close enough to the original one (so that it is within the processed transcript and downstream of a ribosome-binding site) and in frame, it will be used to initiate translation, adding amino acids to the amino terminus of the original protein

As far as I can reason is the only way to create a start codon BEFORE the old one is to change the UTR. As stated in your queation this can only "work" if the UTR parts which have an important function are not affected. Further to get this working the 5'UTR should contain a (not "important" )sequence which can be mutated tot form an AUG (see my explanation above)