Evolution of the Redundancy of the Genetic Code

In short

Looking at the genetic code, it appears that most redundancy is on the third letter rather than on the first or the second letter of the codon. Why has it evolved this way?

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Longer version

In order to compare the relative redundancy accounted by each letter of the codon, let's assume that that every codon occurs at equal frequency. It is probably wrong but useful for the sake of the calculations. Using observed frequencies of codon usage in a given population would change the following probabilities but the question of why some positions in the codon has more redundancy than some others still hold.

A substitution of the first letter of the codon has a probability of $\frac{1}{2048}≈0.00005$ (Stop codon) to be synonymous. A substitution of the second letter of the codon has a probability $\frac{3}{256}≈0.012$ (nucleobases U and G) to be synonymous. A substitution of the third letter has a probability of exactly $\frac{2}{3}$ to be synonymous.

Probability of a substitution to be synonymous given that it occurred on the...

• First letter: $\frac{1}{2048}≈0.00005$


• Second letter: $\frac{3}{256}≈0.012$


• Third letter: $\frac{2}{3}$

Why are there more redundancy on the third position than on the second (which has more redundancy than the first position) in the codon?

Answer

To fully comprehend the concept of wobble base-pairing we need to consider the nucleotide sequences of the anti-codons in the tRNAs that have to "read" the genetic code when the mRNA is being translated on the ribosome. The nucleotide in the anti-codon's wobble position is, for example, often inosine. Under the rules for wobble base-pairing an Inosine can potentially base-pair with three other nucleotides.

In real terms that means a cell can use less than 63 unique tRNA genes to decode mRNAs carrying messages made of the 63 different "words" (codons).

In an active cell the Ribosome's A-site, where the charged tRNA binds, is occupied by the incorrect tRNA most of the time (based on the law of mass action where any charged tRNA can randomly diffuse into the binding site). With tRNAs that can recognize multiple codons (which is what the wobble hypothesis gets us), any given protein can be translated faster (assuming that correct charged tRNAs are limiting for the polypeptide polymerization reaction).

So those are the practical ramifications of the table that you presented, but the explanation, as for most why based questions about biological evolution, is a retrofit. Natural selection can only work with the materials at hand, and so we can infer that during the period when this genetic code was finalized that the organisms who used it were more successful than the others. And the current code is based on whatever the previous one looked like. "Descent by modification" is the original description.

[whoops, sorry about the pedantic voice on the "how selection works" bit, I just looked at your profile and realized you can likely teach me on this subject]