How did the genetic code evolve?

Question

The genetic code is redundant, there are 20 amino acids for 64 possible nucleotide combinations (triplet codons). Therefore some amino acid are coded by several different codons. While leucine is coded by 6 codons, tryptophan is coded only by one codon.

[I am aware that the set of codons that code for one given amino acid tend to look alike each other more than random. Usually it is only the last base that does not affect the amino-acid that is encoded.]

I therefore do not think that the genetic code can be entirely be explained by “it happened to occur that way the first time” (at the origin of life or in the last universal common ancestor) “and it never changed”.

So, my questions are:

• Why are some amino acids coded by a several codons while others are coded only by one or two?

• Specifically, why is methionine coded by only one codon — AUG — which has also to serve as a start signal?

• In general, how (by what mechanisms, selective pressures) has the genetic code evolved to give this pattern of redundancies?

Answer 1

This question is closely related, and the fascinating link posted by @JohnSmith is a good read.

In short, with a four-base system, and a codon size of 1, you get four possible amino acids. Silly system. A codon size of 2 gives 16. Not too shabby, but not a lot of room for growth, and not enough for those 20 amino acids. Codons of size 3 gives 64 - plenty of room to work with and it covers all your forseeable amino acids, and then some, without being too wasteful.

The redundancy, known as degeneracy, is pretty straightforward. There's room to expand, and any redundancy/degeneracy will only reduce the likelihood of errors. That's a huge benefit. For some amino acids, the first two bases are enough. That third position can be quite tolerant to mutation, which is very beneficial to organisms. It appears to be even more fine-tuned, to the degree that redundancy often not only reduces the likelihood of mutation but also reduces the damage caused when a base does mutate. Swapping a hydrophobic AA for another hydrophobic one is less likely to cause aberrant protein function, and anything with a U in the middle is probably hydrophobic. Convenient! I'll also note that, while it's not perfect or even a significant correlation, the more popular amino acids tend to get more redundancy; tryptophan is traditionally the least common AA.

Finally, there are a few non-proteinogenic amino acids, so, as the linked question/answer above points out, maybe in the future there will be more amino acids.

Answer 2

It seems that duplicate codons make translation more robust and resistant to translational misreading. There are four theories that explain existence of duplicate codons:

• Stereochemical theory
• Coevolution theory
• Error minimization theory
• Frozen accident hypothesis

They are not mutually exclusive and “Origin and evolution of the genetic code: the universal enigma” paper attempts to reconcile them:

Mathematical analysis of the structure and possible evolutionary trajectories of the code shows that it is highly robust to translational misreading but there are numerous more robust codes, so the standard code potentially could evolve from a random code via a short sequence of codon series reassignments. Thus, much of the evolution that led to the standard code could be a combination of frozen accident with selection for error minimization although contributions from coevolution of the code with metabolic pathways and weak affinities between amino acids and nucleotide triplets cannot be ruled out. However, such scenarios for the code evolution are based on formal schemes whose relevance to the actual primordial evolution is uncertain. A real understanding of the code origin and evolution is likely to be attainable only in conjunction with a credible scenario for the evolution of the coding principle itself and the translation system.

From my understanding the idea is that codons are grouped by selection for physico-chemical properties of corresponding amino-acids so a random one nucleotide mutation wouldn't change properties or a corresponding amino-acids too dramatic.

Answer 3

Some elements of response to your question.

First, something about tRNA frequency. Even if there are six codons for a given amino acid, they are not equivalent because some will correspond to abundant tRNA, while others correspond to very minor tRNA. This has significant influence on the traduction speed, as the traduction will dramatically slow down on minor tRNA (while the ribosome waits for the proper tRNA). This may have very important impact on the folding of proteins (see for instance this paper: http://dx.doi.org/10.1371/journal.pone.0002189). Having several codons for common amino-acids may actually be a powerful fine-tuning too for the folding of proteins.

Second, as in some cases (splicing, selenocysteine insertion, what else ?), the secondary structure of the mRNA produced is extremely important, the organisms must be able to tweak the sequence of RNA to leave room for that to happen, and that can only happen if there are lots of amino acids for which there is latitude to tweak the produced mRNA sequence.

Third, it is false that the genetic code is universal. There are some evolutions of the genetic code, see for instance the specific case of methionine in mitochondria: http://dx.doi.org/10.1073/pnas.0802779105.