THREE TRANSLATION READING FRAMES 

In both DNA (and the resulting mRNA), three nucleotides code for one amino acid. This is necessary because 20 different amino acid variations are derived from only four bases. Three different peptides can be formed from any sequence depending on the reading frame. To illustrate this, in today's example, we will be looking at the gene SNAPC1, a small RNA activating complex located on Chromosome 14.

In Figure 1, the highlighted section on the main page of the gene is where we will be focusing our attention today. Figure 2 is the zoomed-in section of the highlighted exon within SNAPC1 with individual amino acids visible. In Figure 2, we see that the exon starts with a methionine (ATG codon) and the amino acids are numbered in that frame. The other two frames show the amino acids that would be encoded if the DNA and mRNA were translated beginning with a different nucleotide. This is because the Browser will display the frame beginning with methionine because it actually codes for the protein. This is known as an "open reading frame" and will have no stop codons in the frame.

Figure 1. Main page for the SNAPC1 gene on the hg38 Genome Browser. Highlighted in orange is the example exon we will use to explain reading frames.
https://genome.ucsc.edu/s/education/3frame_fig1

Figure 2. Zoomed-in section of the orange highlighted exon from Figure 1. Here we can see the start codon (methionine) highlighted and green and marked with the number 1 — indicating that the gene starts here. Above are the three different possible reading frames one of which matches the GENCODE V39 track.
https://genome.ucsc.edu/s/education/3frame_fig2

To see the codon numbering for the gene, right-click on the grey bar next to the "GENCODE" track and click "Configure". From here, check the box titled: "Show codon numbering" and click on "Apply". This is shown in Figure 3. To see the other reading frames, click on "Configure" under the "Genome Browser" tab, set "Base Position" to "Full", and finally click "Submit. This is shown in Figure 4.

Figure 3a Right-clicking on the gray bar to the left of the "GENCODE" track will reveal this drop-down menu. From here click "Configure".

Figure 3b "GENCODE" track configuration settings. Here, click the "Show codon numbering" checkbox to show the numbering for the codons.

Figure 4. Track configuration page. At the bottom of the image, we can see the "Base Position" option (red box) where we can set the track to full (then "submit"). In Figures 2 and 5 we can see the results and all three frames.

We can see in Figure 2 that the two other reading frames are different translations of the same nucleotide bases. Which nucleotide base we start with will determine the frame and the corresponding amino acids we will read. Typically, there is only one "correct" frame that gets encoded for the gene SNAPC1, but the other two frames are possible if mutations occur within the exon.

In Figure 5, we can directly observe the other possible amino acid arrangements had we started reading our nucleotides one or two bases downstream. As we already know, ATG codes for methionine, which is the start codon, thus the translation of this gene starts here and is aligned according to this frame. However, had we started creating amino acids a nucleotide before, we would've gotten H or histidine, followed by GDSS etc. The same logic applies if we started two nucleotides back, we would've gotten P or Proline, followed by WGLL etc — totally different proteins.

Figure 5. A close-up example of the three separate reading frames. As stated in the text, which nucleotide you choose to start reading from will determine the amino acids that follow.

Written by Mateo Etcheveste, UCSC.  Major:  BS, Biomolecular Engineering