Polynucleotide phosphorylase

Inference of the Universal Genetic Code from "spiked" monomeric syntheses

    Inferences from assembly of repeating RNA monomers and dimers allow decoding of 16 codons. The monomer synthesis reactions (UUU CCC AAA GGG) can be 'spiked' by adding a small fraction of each of the other three bases in separate reactions. For example, the experiment on the first line in the top box shows that introduction of a small amount of C into a poly-U mix will create a few CUU UCU and UUC codons at random in a predominantly UUU message. UUU produces F (phe) as previously shown, and two of the other three produce L and S as well. The coding arrangement is not obvious. However, given a hypothesis that changing the first or second letter of a codon changes the amino acid, but changing the third doesn't, perhaps UUU and UUC both code for F.

    Working in the same lab at the next bench on the experiment shown on the third line of the second box, introduction of a U spike into a poly-C mix produces UCC, CUC and CCU, and L and S, along with the expected P. Comparison of the two experiments at the next lab meeting shows that both spiked reactions produce L and S, along with P. Given a third-position hypothesis from the first experiment, CCC and CCU probably produce P, and someone will notice that the pairs CUU and CUC, and UCU and UCC, fit this pattern. So, CUN and UCN code for L and S, but which is which is still uncertain.

    Folks working on the experiment on the third line in the third box shows that introduction of a small amount of G into a poly-A mix will create a few GAA, AGA and AAG codons at random in a predominantly AAA message. AAA produces K (xxx) as previously shown, and two of the other three produce E and R as well. Given "Wobble", perhaps AAA and AAG both code for K.

    Workers on a fourth bench on the experiment shown on the third line of the fourth box, find that introduction of an A spike into a poly-G mix produces AGG, GAG, and GGA codons, and amino acids E and R, along with the expected amino acid G. Comparison of the third and fourth experiments over coffee shows that both spiked reactions produce R and E. The "Wobble" hypothesis, as everyone now calls it, predicts GGG and GGA produce amino acid G. Then, the pairs GAA and GAG, and AGA and AGG, also fit the wobble pattern. So, AGN and AGN code for R and E, but which is which is still uncertain.

     Proceed in this fashion to see how many of the codons you can 'crack'. Hint: Among all twelve experimental outcomes, what's unusual about amino acids W and T ?