RT Journal Article SR Electronic T1 A novel nuclear genetic code alteration in yeasts and the evolution of codon reassignment in eukaryotes JF bioRxiv FD Cold Spring Harbor Laboratory SP 037226 DO 10.1101/037226 A1 Stefanie Mühlhausen A1 Peggy Findeisen A1 Uwe Plessmann A1 Henning Urlaub A1 Martin Kollmar YR 2016 UL http://biorxiv.org/content/early/2016/01/19/037226.abstract AB The genetic code is the universal cellular translation table to convert nucleotide into amino acid sequences. Changes to sense codons are expected to be highly detrimental. However, reassignments of single or multiple codons in mitochondria and nuclear genomes demonstrated that the code can evolve. Still, alterations of nuclear genetic codes are extremely rare leaving hypotheses to explain these variations, such as the ‘codon capture’, the ‘genome streamlining’ and the ‘ambiguous intermediate’ theory, in strong debate. Here, we report on a novel sense codon reassignment in Pachysolen tannophilus, a yeast related to the Pichiaceae. By generating proteomics data and using tRNA sequence comparisons we show that in Pachysolen CUG codons are translated as alanine and not as the universal leucine. The polyphyly of the CUG-decoding tRNAs in yeasts is best explained by a tRNA loss driven codon reassignment mechanism. Loss of the CUG-tRNA in the ancient yeast is followed by gradual decrease of respective codons and subsequent codon capture by tRNAs whose anticodon is outside the aminoacyl-tRNA synthetase recognition region. Our hypothesis applies to all nuclear genetic code alterations and provides several testable predictions. We anticipate more codon reassignments to be uncovered in existing and upcoming genome projects.