Evolution of Eukaryal and Archaeal Pseudouridine Synthase Pus10

Abstract

In archaea, pseudouridine (Ψ) synthase Pus10 modifies uridine (U) to Ψ at positions 54 and 55 of tRNA. In contrast, Pus10 is not found in bacteria, where modifications at those two positions are carried out by TrmA (U54 to mU54) and TruB (U55 to Ψ55). Many eukaryotes have an apparent redundancy; their genomes contain orthologs of archaeal Pus10 and bacterial TrmA and TruB. Although eukaryal Pus10 genes share a conserved catalytic domain with archaeal Pus10 genes, their biological roles are not clear for the two reasons. First, experimental evidence suggests that human Pus10 participates in apoptosis induced by the tumor necrosis factor-related apoptosis-inducing ligand. Whether the function of human Pus10 is in place or in addition to of Ψ synthesis in tRNA is unknown. Second, Pus10 is found in earlier evolutionary branches of fungi (such as chytrid Batrachochytrium) but is absent in all dikaryon fungi surveyed (Ascomycetes and Basidiomycetes). We did a comprehensive analysis of sequenced genomes and found that orthologs of Pus10, TrmA, and TruB were present in all the animals, plants, and protozoa surveyed. This indicates that the common eukaryotic ancestor possesses all the three genes. Next, we examined 116 archaeal and eukaryotic Pus10 protein sequences to find that Pus10 existed as a single copy gene in all the surveyed genomes despite ancestral whole genome duplications had occurred. This indicates a possible deleterious gene dosage effect. Our results suggest that functional redundancy result in gene loss or neofunctionalization in different evolutionary lineages.

The human ortholog of archaeal Pus10 produces pseudouridine 54 in select tRNAs where its recognition sequence contains a modified residue

“…Orthologs of archaeal Pus10 are present in most eukaryotes, but not in bacteria and dikaryon fungi including yeast (Watanabe and Gray 2000;Roovers et al 2006;Gurha and Gupta 2008;Fitzek et al 2018). This coincides with the presence of Ψ54 in certain tRNAs of animals, and its absence from the tRNAs of bacteria and yeast (Jühling et al 2009).…”

“…Nuclear and cytoplasmic versions of the Pus10 protein are not the products of paralogous genes. We reported previously (Fitzek et al 2018) that only a single pus10 gene per genome is observed both in archaeal and eukaryotic genomes. This is despite the occurrence of many genome duplications that have occurred during evolution of several eukaryotic lines.…”

“…Previously done multiple sequence alignments (McCleverty et al 2007;Fitzek et al 2018) have shown that though eukaryotic Pus10 proteins are much larger than archaeal Pus10, they do contain the full set of five residues (catalytic Asp, an Arg/Lys, a Tyr/Phe, a hydrophobic residue and a Leu) that are conserved within the active sites of all Ψ synthases (McCleverty et al 2007;Mueller and Ferre-D'Amare 2009). In addition, both archaeal and eukaryotic Pus10 share two more conserved residues with several Ψ synthases: an Arg, two residues N-terminal, and an Asp, two residues C-terminal to the catalytic Asp, which have been shown to be important for the activity of archaeal Pus10 (Joardar et al 2013; Kamalampeta et al 2013;Fitzek et al 2018). The crystal structure of human Pus10 suggests that it is a bona fide Ψ synthase (McCleverty et al 2007).…”

The Emerging Field of Epitranscriptomics in Neurodevelopmental and Neuronal Disorders

“…Pus enzymes are present in all kingdoms of life, evolutionary conserved and are categorized into six families, based on their consensus sequences: TruA, TruB, TruD, RluA, and RsuA. The sixth family member, Pus10, is exclusive to eukaryotes and archaea (Koonin, 1996 ; Kaya and Ofengand, 2003 ; Fitzek et al, 2018 ).…”

Multi-Substrate Specificity and the Evolutionary Basis for Interdependence in tRNA Editing and Methylation Enzymes

“…In the following pages, we will discuss in greater detail both the nature and evolution of heteromultimeric enzymes, with a focus on methyltransferases and deaminases. A previous review touched on the topic of neofunctionalization in the context of pseudouridine synthases (Fitzek et al, 2018). Here neofunctionalization will be only discussed in passing.…”