Dramatic events in ciliate evolution: alteration of UAA and UAG termination codons to glutamine codons due to anticodon mutations in two Tetrahymena tRNAs.

The three major glutamine tRNAs of Tetrahymena thermophila were isolated and their nucleotide sequences determined by post-labeling techniques. Two of these tRNAs show unusual codon recognition: a previously isolated tRNA(UmUA) and a second species with CUA in the anticodon (tRNA(CUA)). These two tRNAs recognize two of the three termination codons on natural mRNAs in a reticulocyte system. tRNA(UmUA) reads the UAA codon of alpha-globin mRNA and the UAG codon of tobacco mosaic virus (TMV) RNA, whereas tRNA(CUA) recognizes only UAG. This indicates that Tetrahymena uses UAA and UAG as glutamine codons and that UGA may be the only functional termination codon. A notable feature of these two tRNAs is their unusually strong readthrough efficiency, e.g. purified tRNA(CUA) achieves complete readthrough over the UAG stop codon of TMV RNA. The third major tRNA of Tetrahymena has a UmUG anticodon and presumably reads the two normal glutamine codons CAA and CAG. The sequence homology between tRNA(UmUG) and tRNA(UmUA) is 81%, whereas that between tRNA(CUA) and tRNA(UmUA) is 95%, indicating that the two unusual tRNAs evolved from the normal tRNA early in ciliate evolution. Possible events leading to an altered genetic code in ciliates are discussed.