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How is Open Reading Frame (ORF) chosen?

Biology Asked on June 30, 2021

I understand that AUG is the "start codon", and, because of this, most proteins begin with methionine as their first amino acid.

However, this ORF problem on Rosalind.info states that "AUGCUGAC… can be translated as …AUGCUG…, …UGCUGA…, and …GCUGAC". That is, something (the Ribosome? The GTP cap mentioned here? Something else?) must cause the translation to be shifted by one or two nucleotides in the sequence.

My first question is : What mechanism(s) cause(s) this shift in translation to another Open Reading Frame (ORF)?

Specifically, I want to know how the start codon, AUG, can have one ("A") or two ("AU") of its bases ignored in the Ribosome during translation.

My second question is : How often does this happen? That is, what is the percentage of (known) proteins that start with methionine vs. the percentage that start with something else due to this "ignoring" of the bases of the start codon?

I am interested in the answers for both prokaryotes and eukaryotes.

One Answer

Tl Dr: In the rosalind example they are showing the 3 reading frames that stem from the definition of a reading frame(non-overlapping triplets), not an example of open reading frames. Open reading frames are non-overlapping triplets between a start codon and a stop codon.

Its important to step back and understand what is meant by reading frame first. It has been determined experimentally that translation occurs in non-overlapping triplets. That is to say that if the ribosome starts reading at position n it will translate n, n+1, and n+2 into an amino acid, then it will start at the next non-overlapping position which is n+3. For example, in the sequence: ABCABCABCABC if you start at A it will read ABC ABC ABC.... But if you start at B you will have an equally valid reading frame by the definition of a non-overlapping triplet and it will read BCA BCA BCA. If you start at C it will read CAB CAB CAB. What would happen if I start at the next A? ABC ABC ABC... See how you are back in the first reading frame? No matter how long a given sequence it will only have 3 reading frames.

Why does that matter if they all start at an AUG? You don't know which AUG translation starts at. Not all AUGs are actually used as the first codon in translation, in fact, most are either internal to a translated protein or not translated at all. An open reading frame is any sequence starting from an AUG to a stop codon. An open reading frame can be within another open reading frame. E.g: AUGCTAUGGCGAUGUUAGAUGA. All of the valid open reading frames are:

    AUGCTAUGGCGAUGUUAGAUGACUAACUAA 

    AUG CTA UGG CGA UGU UAG
         AUG GCG AUG GUU AGA UGA 
               AUG UUA GAU GAC UAA
                      AUG ACU AAC UAA

Answered by Joshua Morris on June 30, 2021

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