A limited number of non-canonical genetic codes have been described in eukaryotic nuclear genomes. Most involve reassignment of one or two termination codons as sense ones [1-4], but no code variant is known that would have reassigned all three termination codons. Here, we describe such a variant that we discovered in a clade of trypanosomatids comprising nominal Blastocrithidia species. In these protists, UGA has been reassigned to encode tryptophan, while UAG and UAA (UAR) have become glutamate encoding. Strikingly, UAA and, less frequently, UAG also serve as bona fide termination codons. The release factor eRF1 in Blastocrithidia contains a substitution of a conserved serine residue predicted to decrease its affinity to UGA, which explains why this triplet can be read as a sense codon. However, the molecular basis for the dual interpretation of UAR codons remains elusive. Our findings expand the limits of comprehension of one of the fundamental processes in molecular biology.

Institute of Environmental Technologies Faculty of Science University of Ostrava Chittussiho 10 710 00 Ostrava Czech Republic

Institute of Parasitology Czech Academy of Sciences Branišovská 31 370 05 České Budějovice Czech Republic

Life Science Research Centre Department of Biology and Ecology Faculty of Science University of Ostrava Chittussiho 10 710 00 Ostrava Czech Republic

Zoological Institute of the Russian Academy of Sciences Universitetskaya nab 1 199034 Saint Petersburg Russia

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