From wikipedia, in the section on the RNA codon table, I see a mapping between codons and amino acids. There, Valine is related to GUU, GUA, GUG, GUC.

Does it mean in the same context that these four codons are interchangeable? Could one replace GUU with GUG?

  • 2
    $\begingroup$ Yes, those codons can be exchanged to get the same amino acid, but it might affect how much protein is made, see codon usage bias $\endgroup$
    – user137
    Jan 28, 2015 at 0:17
  • $\begingroup$ There are some subtle nuances, as well: ncbi.nlm.nih.gov/pubmed/11943474 $\endgroup$
    – canadianer
    Jan 28, 2015 at 0:30
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    $\begingroup$ You seem to have read the table a little wrong: T doesn't appear in RNA. Probably you meant GUG, not GUT. $\endgroup$
    – Leon Avery
    Jan 28, 2015 at 2:11
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    $\begingroup$ @LeonAvery - yes - I read it wrong. thanks for the correction. Corrected in question. $\endgroup$
    – Yehosef
    Jan 28, 2015 at 7:49
  • $\begingroup$ In Spinal Muscular Atrophy (SMA) a single nucleotide C to T transition mutation occurs in SMN2 gene sequence at 840 that produces the same phenylalanine but it gives rise to some translational enhancer/silencer interactions, so intended final protein lacks exon7, gets unstable and shortlived and patients suffer from lack of motor-neuron functions which lead to paralysis. $\endgroup$
    – kenn
    Feb 17, 2019 at 11:46

2 Answers 2


I think given that you're just getting started with genetics, you can say that the codons are interchangeable. This is generally true, though not technically correct. Here are a few reasons for why this is the case, though there's probably more:

  • Specific organisms use specific codons with different frequencies. This is usually related to the tRNA abundance in the cell. Using a codon for which there is relatively less tRNA available would be expected to lead to a decreased protein synthesis rate.
  • Using different codons can affect mRNA secondary structure, which could affect expression.
  • Some codons, especially stop codons, can influence translation contextually through a process called recoding. This can include frame-shifting, read-throughs, cleavage or, perhaps most famously, coding for the amino acid selenocysteine and much more. See here.
  • Different codons can also influence translation contextually through pausing. This affects the rate of protein synthesis as well as its folding. See here.
  • Changing codons can affect regulatory sequences such as miRNA binding sites. Though these are usually present in the UTRs, they can also occur in the CDS.
  • 3
    $\begingroup$ Nice answer - I was considering posting another but it would be better if you just added this as another bullet point, as it is not mutually exclusive to your suggestions; this paper describes translational pausing of different lengths for different codons, even for the same amino acid, which affects protein 3D structure as well - so it would appear that codons in the DNA have another layer of information beyond that of simply saying which amino acid to add to the protein next! $\endgroup$
    – Luke
    Jan 30, 2015 at 13:21
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    $\begingroup$ In addition, changing the codons could affect silencing or modifications by siRNA, miRNA etc. $\endgroup$
    – suvidu
    Feb 4, 2015 at 14:21

A good answer is already provided by @canadianer, but as with many things in biology it is important to keep in mind what organism and/or cell type we are talking about. Because the nuances of the answer to a question about a seemingly universal process sometimes actually depend on whether we want to know about bacteria, or fungi, or mammalian stem cells, etc.

So I think the answer to your question is that synonymous codons are not always interchangeable because of what @canadianer described, but regulation of codon usage is probably more relevant in context of prokaryotes.

For example, for sure availability of a particular synonymous tRNA can be rate limiting in protein synthesis in prokaryotes, but I actually haven't heard of this happening in a eukaryotic system. If there are demonstrated examples, please paste it in the comment..

Also, the secondary structure of the coding part of mRNA is probably less important in eukaryotes, since they have a multitude of ubiquitous RNA-binding proteins that practically coat mRNA (e.g. hnRNP in the nucleus, and probably something similar in the cytoplasm, too)


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