A novel nuclear genetic code alteration in yeasts and the evolution of codon reassignment in eukaryotes

Abstract

The genetic code is the cellular translation table for the conversion of nucleotide sequences into amino acid sequences. Changes to the meaning of sense codons would introduce errors into almost every translated message and are expected to be highly detrimental. However, reassignment of single or multiple codons in mitochondria and nuclear genomes, although extremely rare, demonstrates that the code can evolve. Several models for the mechanism of alteration of nuclear genetic codes have been proposed (including "codon capture," "genome streamlining," and "ambiguous intermediate" theories), but with little resolution. Here, we report 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 Pachysolen translates CUG codons as alanine and not as the more usual leucine. The Pachysolen tRNA CAG is an anticodon-mutated tRNA Ala containing all major alanine tRNA recognition sites. 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 not part of 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.

Genome Diversity and Evolution in the Budding Yeasts (Saccharomycotina)

“…It has occurred several times during yeast evolution as a result of distinct mechanisms (Mühlhausen et al 2016). In P. tannophilus , representing a basal lineage to the methylotroph clade, as well as in A. rubescens , a member of the Ascoidaceae family, the CUG codon specifies alanine instead of leucine or serine (Riley et al 2016).…”

“…In P. tannophilus , representing a basal lineage to the methylotroph clade, as well as in A. rubescens , a member of the Ascoidaceae family, the CUG codon specifies alanine instead of leucine or serine (Riley et al 2016). In P. tannophilus , reassignment followed tRNA loss (Mühlhausen et al 2016). Several different sense-to-sense codon reassignments are also observed in the mitochondrial genetic code of the Saccharomycetaceae yeasts (Ling et al 2014, for a recent overview).…”

Why mitochondria need a genome revisited

“…In effect, several protein‐coding genes are overlapping and termination codons are added after transcription. Moreover, the genetic code has been altered in response to the reductive forces such that it can be read with only 22 tRNA, whereas a minimum of 24 tRNA is required to read the standard genetic code . However, the mitochondrial genome in other organismal groups has not evolved under the same constraints on genome size.…”

Rewriting the Genetic Code

“…Given the vast amount of new genomic and metagenomic DNA sequence information generated in the past few years, we document here the current knowledge of natural deviations from the standard genetic code (45, 61, 79, 92, 94, 98, 115, 125, 134, 157) (Figure 2) (Supplemental Figure 1). Previously, it was well known that Candida yeast reassigns the CUG codon from leucine (Leu) to serine (Ser) (60) and that many ciliates reassign either the UGA stop codon or both the UAA and the UAG stop codons to a canonical amino acid (12, 61, 88, 119) (Figure 2).…”