DNA is made of 4 unique nucleotides. When coding for a protein, a sequence of 3 nucleotides is used to code for each amino acid. Why are codons 3 nucleotides in length?

A related question can be found here: why-are-there-exactly-four-nucleobases-in-dna

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    $\begingroup$ I have asked and answered this here because I had posted this answer to the linked question, but that was not truely answering it. There are now much better alternative answers, so I have asked the question I actually answered here! $\endgroup$
    – Luke
    Commented Jan 26, 2013 at 11:56
  • $\begingroup$ Your question should be more properly (or rather for clarificational purposes) as nitrogenous bases. I think your query confused me a bit. An article I found online explains this in a more-or-less feasible way: biologie.uni-hamburg.de/b-online/e21/21a.htm $\endgroup$
    – user6641
    Commented May 7, 2014 at 4:54

4 Answers 4


The central dogma of molecular biology: DNA makes RNA makes Protein

DNA is a reference for proteins*, which are the functional molecules in cells. These are comprised of 20 unique amino acids, and each is coded for by a stretch of DNA known as a codon. Codons are always 3 base-pairs (nucleotides) in length.

DNA is made of 4 unique nucleotides; (A)denine, (G)uanine, (C)ytosine and (T)hymine. This means that there are 64 unique codons that can be made with these 4 bases (4*4*4).

Theory One - evolvability

If codons were only 2 bases in length then the variety of codons that could be created would be less (only 16 unique sequences if there are still 4 nucleotides). More unique nucleotides would be required to get enough unique sequences to code for the 20 amino acids (as well as the STOP codons). For instance, to get 64 unique sequences using a 2-bases-per-codon system there would need to be 8 unique nucleotides.

We cannot ever 'know' what happened in evolutionary terms, but it seems likely that the 3-base (nucleotide) codon system would have arisen after a period of a 2-base system, as the biological systems became more complex. This would have allowed a lot more variation in the amino-acids used, and thus more "evolvability", which would have been very advantageous to early organisms.

However as the 4-unique-nucleotide/3-codon system is ubiquitous to all life we have discovered on earth, it seems likely that, back at the start of DNA (in fact probably RNA), this was the system that worked, or at least, this is the one that survived (although as Kevin rightly points out, we don't know whether there ever were any other systems). Variations may have arisen over the years, but it is this 1 system that has prevailed here on Earth.

See this question for some more interesting info: why-20-amino-acids-instead-of-64?

Theory Two - "redundancy" of codons conveys additional information

This theory is not mutually exclusive to the one described above. In a recent paper D'Onofrio and Abel [1] state that ribosomes pause for different lengths of time at different codons (even if the codon codes for the same amino acid), and that this pausing affects the 3-dimensional structure of the final protein.

Therefore the nucleotide sequence contains at least two "layers" of information: firstly which amino-acid should be added, and second the specific codon used for that amino acid can impact on the final structure of the protein. This could not be done with fewer nucleotides, but arguably even more control could be exerted with more nucleotides, but perhaps this comes back to my first point that this system evolved such a long time ago that more nucleotides were not necessary for life to "work" and proliferate into everything we see today.

  1. D'Onofrio and Abel, 2014. Frontiers in Genetics. Redundancy of the genetic code enables translational pausing

*only around 1% of our genome is actually protein-coding, and many non-protein-coding RNA products have very important functions, but I won't go into this here. Suffice it to say I am referring to the protein-coding regions of the DNA.

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    $\begingroup$ Overall, this is a good answer. I take issue though with saying "determined that the most efficient". We have no idea that other combinations ever existed. 4 nucleotides in combinations of 3 did not not work. That's all we know. $\endgroup$
    – kmm
    Commented Jan 26, 2013 at 14:24
  • $\begingroup$ @Kevin thanks, and you are absolutely right. I have given the answer a general re-work because I don't think it flowed properly having been adapted from a different question, and have taken your comment into account. Many thanks. $\endgroup$
    – Luke
    Commented Jan 26, 2013 at 16:30
  • $\begingroup$ The comment is NOT a criticism toward the answer. I know everybody is talking about the central dogma of molecular biology but it is such a bad name. Dogma has no place in science. Moreover, we now know that retrotranscription exist and therefore the central dogma of molecular biology not always true. $\endgroup$
    – Remi.b
    Commented Apr 6, 2015 at 19:37
  • $\begingroup$ Thank you for posting the theory two part. I've always wondered why CAG trinucleotide repeat in HTT can cause Huntington's, but CAACAG doesn't seem to. $\endgroup$ Commented Apr 7, 2016 at 5:13
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    $\begingroup$ Man, my BSc thesis (8 years ago) was based on the idea of different codons causing conformational change. I compared the codons of structured-regions in proteins with unstructured and found that codon usage was different when coding for the same amino-acid. The guy who marked it gave me 20%. Led to me getting a low final grade. Required I got my masters before my PhD. Probably set me back 2 years. And now it's published in Frontiers in Genetics -_- Academia sucks when you're small-fry. $\endgroup$
    – J.J
    Commented Nov 22, 2016 at 16:52

I think a strong case can be made for three nt codons existing already in the primordial genetic code, which included only eight abiotic amino acids (this is still clearly seen today in translation tables where most abiotic amino acids are defined by four or more codons). However, in this primordial genetic code, the last nt was likely meaningless (this has been reinvented in many mitochondrial genomes where a single tRNA, usually thanks to a modified U in the anticodon wobble position, recognizes up to 4 codons). Assuming the three nt codon primordial genetic code existed, we see that the reason for the three nt codon structure was not that two nt codon structure was not enough for coding everything (4^2 > 9, it would have sufficed), but something else. So what could it be? My educated guess is that it has to do with the A,P,E-site structure of the ribosome not fitting into a smaller molecular configuration (i.e. you couldn't have the adjacent A,P,E-sites within the space limited by just five phosphodiester bonds (six nt, three two nt codons) vs. eight phosphodiester bonds (nine nt, three three nt codons)). So in short, my view is that the primordial ribosomal structure was the key factor to the three nt codon structure of the genetic code, it couldn't have worked with anything less and anything more would have been a waste.

  • $\begingroup$ This is very interesting information (sorry for delay in commenting). Could you provide any references/additional reading? $\endgroup$
    – Luke
    Commented Jan 14, 2015 at 11:32

Might I suggest you go directly to the source? Here is a link to a paper published by Francis Crick (et al) in 1957 entitled: 'Codes Without Commas' http://www.ncbi.nlm.nih.gov/pmc/articles/PMC528468/

  • $\begingroup$ The source you linked is really good, but simple linking is not exactly what this site is about. Of course it's easier, but please take time and elaborate your answer, explain, interpret the sources you use. $\endgroup$ Commented Apr 6, 2015 at 19:13
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    $\begingroup$ Welcome to Biology.SE. A link only is not sufficient for an answer. Either take time to elaborate your answer or convert your answer to a comment. $\endgroup$
    – Remi.b
    Commented Apr 6, 2015 at 19:35

For the same reason there are 8 bits in a regular character datatype in old-school programming languages (before internationalization and Unicode).

In modern ASCII interpretations, you have a certain number of characters that need to be encoded, somewhere between 128 and 256. 8 bits would be the minimum sufficient for (modern extended) ASCII encoding. (Unrelated to the question: in computing, it often helps to have the number of bits in various operations be a power of 2. Also, the original versions of ASCII specified 7-bit encoding before it was extended to a full byte in an early internationalization support effort.)

Getting back to nucleotides, there are 20 amino acids. Think of a codon as the equivalent of a "byte" and a base (nucleotide) as the equivalent of a "bit". 2-codon sets would be insufficient except if you plan to custom-build a compact-genome life-form that only supports 15 amino acids, a stop codon, and no wobbles.

Supporting all amino acids plus a stop codon requires at least 21 distinct codon values. In particular, find the smallest power of 4 >= 21, which turns out to be 3.

An added bonus: the number of codon values is roughly triple the number or amino acids (plus a stop codon), allowing for redundancy: some amino acids are encoded by more than one codon, which acts as a buffer against mutations.


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