Evolution of non-standard genetic codes in single-celled eukaryotes

What is it about?

This study explores the evolution of the genetic code in ciliates, a lineage of single-celled protists. The genetic code dictates the translation of nucleotide sequences into amino acids. Most organisms use the “standard genetic code”, which has three stop codons (UAA, UAG, and UGA) to signal the end of genes during translation of mRNA to proteins. Here, we report multiple instances where the UAG stop codon has been reassigned to function as a sense codon to encode amino acids. Analysing marine metagenomic data from the TARA Oceans Project, we identified three species from an uncultivated lineage of phyllopharyngean ciliates that use the UAG codon to encode leucine. Extending our analysis to include other genomes from the Phyllopharyngea class, we identified further changes in Hartmannula sinica and Trochilia petrani, where the UAG codon has been reassigned to encode glutamine. Using phylogenomic approaches, we show that three lineages within Phyllopharyngea independently reassigned the UAG stop codon to encode amino acids.

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Photo by Sangharsh Lohakare on Unsplash

Photo by Sangharsh Lohakare on Unsplash

Why is it important?

The "standard genetic code" was once thought to be immutable given its near universality across the tree of life. The discovery of alternative genetic codes over the last five decades has shown that this is not the case. Our work shows that there are still unexplored genetic code reassignments awaiting discovery in poorly sampled environments and branches of the tree of life. Our discovery of three independent genetic code change events within a single ciliate lineage highlights the evolvability of the genetic code. In most reported variants of the genetic code, the function of the UAA and UAG codons are coupled. Here, we show that UAG has evolved as a sense codon independently of the UAA codon which is retained as a stop codon. These findings broaden our understanding of genetic code evolution and expand the remarkable diversity of genetic codes employed by ciliates. Understanding how non-standard genetic codes evolve in nature is essential to be able to engineer efficient and stable synthetic genomes with altered genetic codes.

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