Nuclear genetic codes with a different meaning of the UAG and the UAA codon

Abstract

BackgroundDepartures from the standard genetic code in eukaryotic nuclear genomes are known for only a handful of lineages and only a few genetic code variants seem to exist outside the ciliates, the most creative group in this regard. Most frequent code modifications entail reassignment of the UAG and UAA codons, with evidence for at least 13 independent cases of a coordinated change in the meaning of both codons. However, no change affecting each of the two codons separately has been documented, suggesting the existence of underlying evolutionary or mechanistic constraints.ResultsHere, we present the discovery of two new variants of the nuclear genetic code, in which UAG is translated as an amino acid while UAA is kept as a termination codon (along with UGA). The first variant occurs in an organism noticed in a (meta)transcriptome from the heteropteran Lygus hesperus and demonstrated to be a novel insect-dwelling member of Rhizaria (specifically Sainouroidea). This first documented case of a rhizarian with a non-canonical genetic code employs UAG to encode leucine and represents an unprecedented change among nuclear codon reassignments. The second code variant was found in the recently described anaerobic flagellate Iotanema spirale (Metamonada: Fornicata). Analyses of transcriptomic data revealed that I. spirale uses UAG to encode glutamine, similarly to the most common variant of a non-canonical code known from several unrelated eukaryotic groups, including hexamitin diplomonads (also a lineage of fornicates). However, in these organisms, UAA also encodes glutamine, whereas it is the primary termination codon in I. spirale. Along with phylogenetic evidence for distant relationship of I. spirale and hexamitins, this indicates two independent genetic code changes in fornicates.ConclusionsOur study documents, for the first time, that evolutionary changes of the meaning of UAG and UAA codons in nuclear genomes can be decoupled and that the interpretation of the two codons by the cytoplasmic translation apparatus is mechanistically separable. The latter conclusion has interesting implications for possibilities of genetic code engineering in eukaryotes. We also present a newly developed generally applicable phylogeny-informed method for inferring the meaning of reassigned codons.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-017-0353-y) contains supplementary material, which is available to authorized users.

Translation Termination and Ribosome Recycling in Eukaryotes

“…The canonical genetic code has three stop codons (UAA, UAG, and UGA), and the efficiency of termination is enhanced by a purine residue in the +4 position and by a +5 purine if the +4 residue is a pyrimidine (McCaughan et al 1995). In a few organisms, including some ciliate protists, green algae, and diplomonads, UGA is reassigned as a sense codon and UAA and UAG are retained as stop codons, UAA and UAG are reassigned as sense codons with UGA as the sole termination codon, or UAG is reassigned as a sense codon and UAA and UGA function as stop codons (Keeling 2016;Pánek et al 2017).…”

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).…”

“…Recent eukaryotic genome/transcriptome analyses identified that ( a ) Pachysolen tannophilus , a yeast species distinct from Candida spp., reassigns CUG to alanine (Ala; 92, 125) (Figure 2); ( b ) diverse single-celled eukaryotes that are nonciliate also reassign stop codons to amino acids (17, 19, 59, 62, 63, 115, 157) (Figure 2); ( c ) not only Gln but also Leu, tyrosine (Tyr), and glutamic acid (Glu) are assigned to UAR [R denotes adenosine (A) and guanine (G)] (45, 134) or to UAG (115) (Figure 2); and ( d ) ciliates Parduczia sp. and Condylostoma magnum and trypanosomatids Blastocrithidia spp.…”

Visual mate preference evolution during butterfly speciation is linked to neural processing genes

“…Changes in sensory perception or other neural systems must underlie differences in innate behaviours between species, and will ultimately have a genetic basis. Although the significance of behavioural barriers for speciation has been recognized since the Modern Synthesis 3 , we know little of the genes underlying changes in mating preferences, or variation in behaviours across natural populations more broadly 4 . Identifying these genes will provide an important route towards understanding how behavioural differences are generated, both during development and across evolutionary time.…”