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I am learning about frameshift mutations. Frameshifts can occur due to a nucleotide deletion. Suppose that due to a frameshift, because of a deletion somewhere upstream from the original start codon, two additional start codons are generated, just before the stop codon in the new reading frame. What would happen in terms of translation?

AUG-GCC-AUA-AUG--------UAA Start Start then stop

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    $\begingroup$ If one of these answers solved your issue, please take a moment and accept it by clicking on the check mark to the left. That will mark the question as answered and is the way thanks are expressed on the Stack Exchange sites. $\endgroup$ – terdon Oct 4 '15 at 20:29
  • $\begingroup$ This is an old question, but it should say, or the answers should say, whether they are referring to eukaryotic or prokaryotic systems. All the answers appear to assume eukaryotic systems. $\endgroup$ – David Feb 23 '17 at 17:32
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There is a basic misconception in the question you have asked, which @biogirl has explained. There is only one start Codon in any mRNA and it defines the open reading frame.

All other AUGs in the open reading frame are simply codons that encode for the Amino Acid Methionine and have no function in the start of translation. There are factors other than AUG that determine the start of translation.

So a frame shift that gives you an additional AUG only means that you will have a different Amino Acid encoded for in the resulting polypeptide. A frame shift will generally completely alter the protein product of the gene. If however the frameshift does disrupt the start codon, then it is unlikely that you will have any translation what-so-ever, as the other elements necessary for determining the start of translation will likely not be present in other areas of the coding sequence. In prokaryotes, you need a Shine-Delgarno sequence to initiate translation, and in Eukaryotes, though all of the factors for translation start are not well understood many genes carry a Kozak sequence that indicates to the ribosome the start of the open reading frame.

The more important codons to look for are introductions of stop codons. These three codons, UAA, UAG, and UGA do not have tRNAs with complementary anticodons (for the most part, as tRNA genes can also sustain mutations that change their anticodon) and therefore all result in the termination of translation if the shifted frame results in the ribosome reading one of the three stop codons in frame.

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    $\begingroup$ Very good answer and +1. Just a nitpick: strictly speaking, there are actually tRNAs that recognize STOP codons. Such nonsense tRNAs can be the product of a specific mutation but also, as is the case for tRNASec, wild type sequences that insert a specific amino acid. $\endgroup$ – terdon Oct 4 '15 at 20:38
  • $\begingroup$ @terdon, Learn something new (or old as this was discovered in the 80's) every day. I had a hard time finding references, but Molecular Biology of the Cell 6th Edition mentions selenocysteine and it does indeed have an ACU anti-codon. It looked like there needs to be a secondary stem-loop structure in the mRNA for it to be incorporated instead of having a release factor bind and terminate transcription, but it definitely shows the remarkable flexibility and diversity of the genetic code. Thanks! $\endgroup$ – AMR Oct 4 '15 at 21:58
  • $\begingroup$ mRNAs can include multiple start codons (and thus multiple ORFs). Upstream AUGs and their effect on translational regulation are an active area of research. They are also sensitive to neighboring mutations. science.sciencemag.org/content/352/6292/1413 $\endgroup$ – boloyao Mar 14 '17 at 2:47
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AUG functions as a start codon only when it is at the 1st position of the open reading frame. Whenever AUG is present in between, it codes for methionine amino acid. Go through the basics of translation from a good book.

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The start codon is not sufficient to start translation. A ribosomal binding site is also required. It's likely that translation would initiate at its normal location and then simply proceed through any additional start codons in the new ORF until it reaches the first stop codon.

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  • $\begingroup$ That is half the story as it is only in Prokaryotes that the ribosome binds to the Shine-Delgarno sequence and the starting AUG. In Eukaryote small ribosomal subunits bind near the 5' cap and scan through the 5' UTR until the Start codon. In many mRNAs that is near the Kozak sequence, but not all Eukaryotic mRNAs have a Kozak sequence. $\endgroup$ – AMR Oct 4 '15 at 4:48
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    $\begingroup$ @AMR Nowhere in my answer did I make the claims you say I did. The ribosomal binding site is self explanatory, be it the SD sequence or 5' cap. $\endgroup$ – canadianer Oct 4 '15 at 5:04
  • $\begingroup$ It is because you are answering a questionabout two AUGs, and you are saying that there needs to be a ribosomal binding site, which is correct, but when taken with the question implies that the ribosome is choosing between one or the other AUG based on where it binds, and that would only be relevant in the case of prokaryotes as it would bind to the AUG in the SD sequence. Eukaryotes would scan to the start site. AUG is simply the codon for methionine so even saying additional start codons as you have in your edit obfuscates the situation. $\endgroup$ – AMR Oct 4 '15 at 5:16
  • $\begingroup$ @AMR I really don't understand your point. The start codon is chosen based on where the ribosome binds. What is the controversy? $\endgroup$ – canadianer Oct 4 '15 at 5:21
  • $\begingroup$ In Eukaryotes you can have an AUG or multiple AUGs in the 5'UTR, so your last comment doesn't hold, and your answer is not complete and is confusing. Eukaryotic translation does not necessarily begin with the first AUG encountered. And as I pointed out before, there is one start codon, which defines the open reading frame; any other AUGs are methionine codons or are in the UTRs and are untranslated, so no additional AUG is called a start codon. $\endgroup$ – AMR Oct 4 '15 at 7:47

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