Endogenous Stochastic Decoding of the CUG Codon by Competing Ser- and Leu-tRNAs in Ascoidea asiatica

Abstract

SummaryAlthough the “universal” genetic code is now known not to be universal, and stop codons can have multiple meanings, one regularity remains, namely that for a given sense codon there is a unique translation. Examining CUG usage in yeasts that have transferred CUG away from leucine, we here report the first example of dual coding: Ascoidea asiatica stochastically encodes CUG as both serine and leucine in approximately equal proportions. This is deleterious, as evidenced by CUG codons being rare, never at conserved serine or leucine residues, and predominantly in lowly expressed genes. Related yeasts solve the problem by loss of function of one of the two tRNAs. This dual coding is consistent with the tRNA-loss-driven codon reassignment hypothesis, and provides a unique example of a proteome that cannot be deterministically predicted.Video Abstract

Genomic and ecological factors shaping specialism and generalism across an entire subphylum

“…Despite a predicted CAG-tRNA with a valine isotype, a computational screen of gene sequences did not predict a novel reassignment. The diversity of tRNA species in the Ascoideales is consistent with previous findings that its member species may stochastically decode CUG as both leucine and serine ( 49 ).…”

Genomic and ecological factors shaping specialism and generalism across an entire subphylum

“…Despite a predicted CAG-tRNA with a valine isotype, a computational screen of gene sequences did not predict a novel reassignment. The diversity of tRNA species in the Ascoideales is consistent with previous findings that its member species may stochastically decode CUG as both leucine and serine ( 49 ).…”

A computational screen for alternative genetic codes in over 250,000 genomes

“…JCM 15000) could not be placed into a category and was excluded from the analysis. The expected CUG translation for each clade follows Shen et al, 2018 and is consistent with other studies of CUG translation ( Riley et al, 2016 ; Krassowski et al, 2018 ; Mühlhausen et al, 2018 ). Genetic codes were predicted by Codetta as described above.…”

Proteogenomics analysis of CUG codon translation in the human pathogen Candida albicans

“…Third, we found similar levels of ambiguity for other rare leucine and serine codons which indicates that the observed mistranslation level corresponds to the general ribosomal mistranslation rate. This is further supported by observation of similar mistranslation rates in other yeasts [ 3 , 4 ]. If the assumed 3–5% mistranslation of CUG codons by leucine were below the detection level of our approach, the background ambiguity by ribosomal mistranslation would be at an even higher level.…”

Genomic and ecological factors shaping specialism and generalism across an entire subphylum

“…Despite a predicted CAG-tRNA with a valine isotype, a computational screen of gene sequences did not predict a novel reassignment. The diversity of tRNA species in the Ascoideales is consistent with previous findings that its member species may stochastically decode CUG as both leucine and serine ( 49 ).…”

A computational screen for alternative genetic codes in over 250,000 genomes

“…JCM 15000) could not be placed into a category and was excluded from the analysis. The expected CUG translation for each clade follows Shen et al, 2018 and is consistent with other studies of CUG translation ( Riley et al, 2016 ; Krassowski et al, 2018 ; Mühlhausen et al, 2018 ). Genetic codes were predicted by Codetta as described above.…”

Proteogenomics analysis of CUG codon translation in the human pathogen Candida albicans

“…Third, we found similar levels of ambiguity for other rare leucine and serine codons which indicates that the observed mistranslation level corresponds to the general ribosomal mistranslation rate. This is further supported by observation of similar mistranslation rates in other yeasts [ 3 , 4 ]. If the assumed 3–5% mistranslation of CUG codons by leucine were below the detection level of our approach, the background ambiguity by ribosomal mistranslation would be at an even higher level.…”

Genomic and ecological factors shaping specialism and generalism across an entire subphylum

“…Despite a predicted CAG-tRNA with a valine isotype, a computational screen of gene sequences did not predict a novel reassignment. The diversity of tRNA species in the Ascoideales is consistent with previous findings that its member species may stochastically decode CUG as both leucine and serine ( 49 ).…”

A computational screen for alternative genetic codes in over 250,000 genomes

“…JCM 15000) could not be placed into a category and was excluded from the analysis. The expected CUG translation for each clade follows Shen et al, 2018 and is consistent with other studies of CUG translation ( Riley et al, 2016 ; Krassowski et al, 2018 ; Mühlhausen et al, 2018 ). Genetic codes were predicted by Codetta as described above.…”

Proteogenomics analysis of CUG codon translation in the human pathogen Candida albicans

“…Third, we found similar levels of ambiguity for other rare leucine and serine codons which indicates that the observed mistranslation level corresponds to the general ribosomal mistranslation rate. This is further supported by observation of similar mistranslation rates in other yeasts [ 3 , 4 ]. If the assumed 3–5% mistranslation of CUG codons by leucine were below the detection level of our approach, the background ambiguity by ribosomal mistranslation would be at an even higher level.…”