The aim of the CODEKILLER project was to investigate a possible mechanism by which the genetic code can change during evolution. The genetic code is the set of rules that determine how the 64 different codons in mRNA are translated into the 20 different amino acids in protein molecules, for example the codon AUG is translated into methionine. In the cell, the genetic code is physically implemented by tRNA molecules, which are covalently attached to an amino acid at one end and make basepairs with codons in mRNA at the other end. The genetic code is often considered to be universal because it is the same in the nuclear genomes of most species, but in 2018 we discovered that the genetic code has changed several times during the evolution of budding yeast species. Specifically, the codon CUG, which is translated as leucine in most species, is translated as serine or alanine in some groups of yeasts. Because this change is almost the only evolutionary change in the genetic code that has ever happened during the evolution of nuclear genomes, our goal was to understand how it happened. Our hypothesis was that the evolutionary reassignment of the codon CUG was caused by natural selection imposed by a killer toxin, specifically a ribonuclease toxin that cleaves and destroys tRNA-Leu molecules with the anticodon CAG, which translate CUG codons as leucine. We postulated that many different killer toxins that cleave specific tRNAs may exist in yeasts, even though such toxins are rare and only 4 of them were known at the outset of the CODEKILLER project.
