<p>To add complexity to this discussion, there are examples in some mitochondrial genomes where the stop point of a gene is based on the polyA-attached transcript, rather than the genomic sequence. I worked on a paper about <em>Nippostrongylus brasiliensis</em> mtDNA, and needed polyA completion to explain the transcript expression I observed:</p>
<p><a href="https://doi.org/10.12688/f1000research.10545.1" rel="nofollow noreferrer">https://doi.org/10.12688/f1000research.10545.1</a></p>
<p>There are plenty of other examples of gene transcription happening in a situation other than one-exon-per-fragment: transcription that's on <a href="https://dx.doi.org/10.1101%2Fgr.1590904" rel="nofollow noreferrer">both sides of the DNA</a>, exon sharing for different genes present on the same strand (they're usually <a href="https://doi.org/10.1006/geno.1999.6112" rel="nofollow noreferrer">in the same frame</a>, but there's the MT-ATP6/MT-ATP8 example that @Nuclear_Hoagie pointed out), <a href="https://doi.org/10.1371/journal.pgen.1007764" rel="nofollow noreferrer">micropeptide</a> expression from smaller chunks of genes. Some also have some degree of <a href="https://doi.org/10.7554/eLife.01179.001" rel="nofollow noreferrer">stop-codon read-through</a>, so the stop codons are not a strict stop in all cases. Some viruses are also <a href="https://doi.org/10.1016/0042-6822(86)90011-5" rel="nofollow noreferrer">particularly good</a> at exploiting transcription / translation complexity.</p>

CC BY-SA 4.0
2020-10-26T22:12:16.323Z
Thank you for opening me up to a whole new world of information.  This is all very interesting, and there is a lot to learn.
Jonathan Charlton
CC BY-SA 4.0
2020-10-26T21:48:05.927Z
2020-10-27T02:25:36.890Z
2020-10-27T02:25:36.890Z
gringer
<p>This relates to the concept of the <em><strong>reading frame</strong></em>, which is the point at which you start dividing 3-letter sequences into codons. As you point out, there are multiple ways to divide a string of amino acids into triplets - in fact, there are six unique ways, found by shifting the start letter by one three times, and doing the same but reading in reverse.</p>
<p>Typically, there is one commonly used frame which can be transcribed and turned into protein, called the open reading frame. But it is not unheard of for a single piece of DNA to encode multiple, overlapping genes, depending on where you start reading it. So, the sequence you show cannot encode 13 amino acids in a single string, but it can encode three different strings, one of which has 5 amino acids and the other two which have 4 amino acids each.</p>
<p>See <a href="https://en.wikipedia.org/wiki/Reading_frame#Multiple_reading_frames" rel="nofollow noreferrer">Multiple Reading Frames</a> at Wikipedia, which shows the following example of a single piece of human DNA which encodes two different genes, MT-ATP6 and MT-ATP8.</p>
<p><a href="https://i.sstatic.net/UKklY.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/UKklY.png" alt="enter image description here" /></a></p>

CC BY-SA 4.0
2020-10-26T16:44:24.387Z
This is an awesome answer!  Thank you.
Jonathan Charlton
CC BY-SA 4.0
2020-10-26T16:41:48.117Z
2020-10-26T16:41:48.117Z
Nuclear Hoagie
<p>I am analyzing nucleotide base-pair patterns in RNA and DNA, and had a thought about RNA and DNA (Let me first state though, I am not a biologist; I am an algorithmatician, employing a sort of recursive sequential neural network).</p>
<p>In any event, I was wondering if we are misinterpreting the way that we look at codons in RNA.  Are we?  Are we missing something when we interpret them the way that we do?  A picture is worth a thousand words, so I made a powerpoint slide of my question and screen captured it.  It highlights the specific question I am asking, which is: are codons layered?</p>
<p>Why is this important to me?  When I look at patterns, I know for a fact that unless it is the end of the sequence (a stop codon) that if I have a U-nucleotide, then the next two nucleotides cannot be AA, AG, nor GA.  Additionally, I know that unless there is a U-nucleotide, the sequence will definitely not end in two or less nucleotides.  This is what got me to wondering if there indeed is layered information in the combination of nucleotides.  Please see the picture.</p>
<p>So if we have (as in the picture) an RNA sequence:
AUGGUCAGUCCAUAA</p>
<p>We might interpret that as 5 codons {Methionine, Valine, Serine, Proline, STOP}</p>
<p>But what if there are actually 13 codons: {Methionine, Tryptophan, Glycine, Valine, Serine, Glutamine, Serine, Valine, Serine, Proline, Histidine, Isoleucine, STOP}</p>
<p><a href="https://i.sstatic.net/wpXID.jpg" rel="nofollow noreferrer"><img src="https://i.sstatic.net/wpXID.jpg" alt="What we might be misintepreting about RNA and DNA codons" /></a></p>

CC BY-SA 4.0
2020-10-26T16:52:39.787Z
Read up on "reading frames" - that concept addresses the scenario you bring up here. Every coding sequence has 3 frames: 123 456 789, xx1 234 567 89x and x12 345 678 9xx. Usually, the one producing the longest product is chosen as the "correct" reading frame.
Ram RS
CC BY-SA 4.0
2020-10-26T17:09:02.740Z
They know it's this way through experimentation. They can identify proteins and they have found proteins corresponding to coding using 3 non-overlapped letters and not the other way. It's not interpretation but observation.
juanjo75es
CC BY-SA 4.0
2020-10-26T21:06:54.360Z
Thank you Ram (that's really insightful), and thank you juanjo because that was another question I had about where the 3 comes from.  Your response is helpful because one of the difficulties in researching it beyond assigning 1's and 0's is language that helps you research prior patterns.
Jonathan Charlton
<phylogenetics><sequence-analysis><rna><computational-biochemistry><codon>
Are codons in RNA layered? Are we misinterpreting RNA codons?
# Are codons in RNA layered? Are we misinterpreting RNA codons?

(Asked by: username_0 on 2020-10-26)

I am analyzing nucleotide base-pair patterns in RNA and DNA, and had a thought about RNA and DNA (Let me first state though, I am not a biologist; I am an algorithmatician, employing a sort of recursive sequential neural network).

In any event, I was wondering if we are misinterpreting the way that we look at codons in RNA. Are we? Are we missing something when we interpret them the way that we do? A picture is worth a thousand words, so I made a powerpoint slide of my question and screen captured it. It highlights the specific question I am asking, which is: are codons layered?

Why is this important to me? When I look at patterns, I know for a fact that unless it is the end of the sequence (a stop codon) that if I have a U-nucleotide, then the next two nucleotides cannot be AA, AG, nor GA. Additionally, I know that unless there is a U-nucleotide, the sequence will definitely not end in two or less nucleotides. This is what got me to wondering if there indeed is layered information in the combination of nucleotides. Please see the picture.

So if we have (as in the picture) an RNA sequence:
AUGGUCAGUCCAUAA

We might interpret that as 5 codons {Methionine, Valine, Serine, Proline, STOP}

But what if there are actually 13 codons: {Methionine, Tryptophan, Glycine, Valine, Serine, Glutamine, Serine, Valine, Serine, Proline, Histidine, Isoleucine, STOP}

[![What we might be misintepreting about RNA and DNA codons](https://i.sstatic.net/wpXID.jpg)](https://i.sstatic.net/wpXID.jpg)

**Tags:** phylogenetics, sequence-analysis, rna, computational-biochemistry, codon
> **Comments:**
> **username_1**: Read up on "reading frames" - that concept addresses the scenario you bring up here. Every coding sequence has 3 frames: 123 456 789, xx1 234 567 89x and x12 345 678 9xx. Usually, the one producing the longest product is chosen as the "correct" reading frame.  
> **username_2**: They know it's this way through experimentation. They can identify proteins and they have found proteins corresponding to coding using 3 non-overlapped letters and not the other way. It's not interpretation but observation.  
> **username_0**: Thank you Ram (that's really insightful), and thank you juanjo because that was another question I had about where the 3 comes from.  Your response is helpful because one of the difficulties in researching it beyond assigning 1's and 0's is language that helps you research prior patterns.  

---

## 2 answers

### Answer by username_4 on 2020-10-26. Score: 3 | Accepted answer

This relates to the concept of the ***reading frame***, which is the point at which you start dividing 3-letter sequences into codons. As you point out, there are multiple ways to divide a string of amino acids into triplets - in fact, there are six unique ways, found by shifting the start letter by one three times, and doing the same but reading in reverse.

Typically, there is one commonly used frame which can be transcribed and turned into protein, called the open reading frame. But it is not unheard of for a single piece of DNA to encode multiple, overlapping genes, depending on where you start reading it. So, the sequence you show cannot encode 13 amino acids in a single string, but it can encode three different strings, one of which has 5 amino acids and the other two which have 4 amino acids each.

See [Multiple Reading Frames](https://en.wikipedia.org/wiki/Reading_frame#Multiple_reading_frames) at Wikipedia, which shows the following example of a single piece of human DNA which encodes two different genes, MT-ATP6 and MT-ATP8.

[![enter image description here](https://i.sstatic.net/UKklY.png)](https://i.sstatic.net/UKklY.png)

> **Comments:**
> **username_0**: This is an awesome answer!  Thank you.  

---

### Answer by username_3 on 2020-10-26. Score: 1

To add complexity to this discussion, there are examples in some mitochondrial genomes where the stop point of a gene is based on the polyA-attached transcript, rather than the genomic sequence. I worked on a paper about *Nippostrongylus brasiliensis* mtDNA, and needed polyA completion to explain the transcript expression I observed:

<https://doi.org/10.12688/f1000research.10545.1>

There are plenty of other examples of gene transcription happening in a situation other than one-exon-per-fragment: transcription that's on [both sides of the DNA](https://dx.doi.org/10.1101%2Fgr.1590904), exon sharing for different genes present on the same strand (they're usually [in the same frame](https://doi.org/10.1006/geno.1999.6112), but there's the MT-ATP6/MT-ATP8 example that @Nuclear\_Hoagie pointed out), [micropeptide](https://doi.org/10.1371/journal.pgen.1007764) expression from smaller chunks of genes. Some also have some degree of [stop-codon read-through](https://doi.org/10.7554/eLife.01179.001), so the stop codons are not a strict stop in all cases. Some viruses are also [particularly good](https://doi.org/10.1016/0042-6822(86)90011-5) at exploiting transcription / translation complexity.

> **Comments:**
> **username_0**: Thank you for opening me up to a whole new world of information.  This is all very interesting, and there is a lot to learn.  

---

