Journal of Molecular Evolution

, Volume 86, Issue 1, pp 77–89 | Cite as

Evolution of Eukaryal and Archaeal Pseudouridine Synthase Pus10

  • Elisabeth Fitzek
  • Archi Joardar
  • Ramesh Gupta
  • Matt GeislerEmail author
Original Article


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 m5U54) 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.


Phylogeny Protein evolution Subfunctionalization Pseudogene Orthologs 



This work was supported by NIH Grant GM55045 to R.G.

Supplementary material

239_2018_9827_MOESM1_ESM.docx (51 kb)
Supplementary material 1 (DOCX 50 KB)
239_2018_9827_MOESM2_ESM.docx (17 kb)
Supplementary material 2 (DOCX 16 KB)
239_2018_9827_MOESM3_ESM.docx (75 kb)
Supplementary material 3 (DOCX 75 KB)
239_2018_9827_MOESM4_ESM.docx (90 kb)
Supplementary material 4 (DOCX 90 KB)


  1. Anderson FE, Swofford DL (2004) Should we be worried about long-branch attraction in real data sets? Investigations using metazoan 18S rDNA. Mol Phylogenet Evol 33:440CrossRefPubMedGoogle Scholar
  2. Aravind L, Koonin EV (2001) THUMP—a predicted RNA-binding domain shared by 4-thiouridine, pseudouridine synthases and RNA methylases. TRENDS Biochem Sci 26:215CrossRefPubMedGoogle Scholar
  3. Aza-Blanc P, Cooper CL, Wagner K, Batalov S, Deveraux QL, Cooke MP (2003) Identification of modulators of TRAIL-induced apoptosis via RNAi-based phenotypic screening. Mol Cell 12:627CrossRefPubMedGoogle Scholar
  4. Bates PA, Kelley LA, MacCallum RM, Sternberg MJE (2001) Enhancement of protein modeling by human intervention in applying the automatic programs 3D-JIGSAW and 3D-PSSM. Proteins 45:39CrossRefGoogle Scholar
  5. Becker HF, Motorin Y, Planta RJ, Grosjean H (1997) The yeast gene YNL292w encodes a pseudouridine synthase (Pus4) catalyzing the formation of Ψ55 in both mitochondrial and cytoplasmic tRNAs. Nucleic Acids Res 25:4493CrossRefPubMedPubMedCentralGoogle Scholar
  6. Blaby IK, Majumder M, Chatterjee K, Jana S, Grosjean H, De Crécy-Lagard V, Gupta R (2011) Pseudouridine formation in archaeal RNAs: the case of Haloferax volcanii. RNA 17:1367CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bombarely A, Menda N, Tecle IY, Buels RM, Strickler S, Fischer-York T, Pujar A, Leto J, Gosselin J, Mueller LA (2011) The sol genomics network ( growing tomatoes using Perl. Nucleic Acids Res 39:1149CrossRefGoogle Scholar
  8. Chan CM, Huang RH (2009) Enzymatic characterization and mutational studies of TruD—the fifth family of pseudouridine synthases. Arch Biochem Biophys 489:15CrossRefPubMedGoogle Scholar
  9. Coll NS, Vercammen D, Smidler A, Clover C, Van Breusegem F, Dangl JL, Epple P (2010) Arabidopsis type I metacaspases control cell death. Science 330:1393CrossRefPubMedGoogle Scholar
  10. Conrad J, Niu L, Rudd K, Lane BG, Ofengand J (1999) 16S ribosomal RNA pseudouridine synthase RsuA of Escherichia coli: deletion, mutation of the conserved Asp102 residue, and sequence comparison among all other pseudouridine synthases. RNA 5:751CrossRefPubMedPubMedCentralGoogle Scholar
  11. Foster PG, Huang L, Santi DV, Stroud RM (2000) The structural basis for tRNA recognition and pseudouridine formation by pseudouridine synthase I. Nat Struct Mol Biol 7:23CrossRefGoogle Scholar
  12. Guex N, Peitsch MC (1997) SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18:2714CrossRefPubMedGoogle Scholar
  13. Guex N, Peitsch MC, Schwede T (2009) Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: a historical perspective. Electrophoresis 30:162CrossRefGoogle Scholar
  14. Gurha P, Gupta R (2008) Archaeal Pus10 proteins can produce both pseudouridine 54 and 55 in tRNA. RNA 14:2521CrossRefPubMedPubMedCentralGoogle Scholar
  15. Hamilton CS, Spedaliere CJ, Ginter JM, Johnston MV, Mueller EG (2005) The roles of the essential Asp-48 and highly conserved His-43 elucidated by the pH dependence of the pseudouridine synthase TruB. Arch Biochem Biophys 433:322CrossRefPubMedGoogle Scholar
  16. Hamma T, Ferré-D’Amaré AR (2006) Pseudouridine synthases. Chem Biol 13:1125CrossRefPubMedGoogle Scholar
  17. Helm M (2006) Post-transcriptional nucleotide modification and alternative folding of RNA. Nucleic Acids Res 34:721CrossRefPubMedPubMedCentralGoogle Scholar
  18. Hoang C (2004) Crystal structure of the highly divergent pseudouridine synthase TruD reveals a circular permutation of a conserved fold. RNA 10:1026CrossRefPubMedPubMedCentralGoogle Scholar
  19. Hoang C, Ferré-D’Amaré AR (2001) Cocrystal structure of a tRNA55 pseudouridine synthase: nucleotide flipping by an RNA-modifying enzyme. Cell 107:929CrossRefPubMedGoogle Scholar
  20. Hoang C, Chen J, Vizthum CA, Kandel JM, Hamilton C, Mueller EG, Ferré-D’Amaré AR (2006) Crystal structure of pseudouridine synthase RluA: indirect sequence readout through protein-induced RNA structure. Mol Cell 24:535CrossRefPubMedGoogle Scholar
  21. Holm L, Rosenstrom R (2010) Dali server: conservation mapping in 3D. Nucleic Acids Res 38:W545CrossRefPubMedPubMedCentralGoogle Scholar
  22. Holm L, Kääriäinen S, Rosenström P, Schenkel A (2008) Searching protein structure databases with DaliLite v.3. Bioinformatics 24:2780CrossRefPubMedPubMedCentralGoogle Scholar
  23. Hubbard TJP, Aken BL, Ayling S, Ballester B, Beal K, Bragin E, Brent S, Chen Y, Clapham P, Clarke L, Coates G, Fairley S, Fitzgerald S, Fernandez-Banet J, Gordon L, Graf S, Haider S, Hammond M, Holland R, Howe K, Jenkinson A, Johnson N, Kahari A, Keefe D, Keenan S, Kinsella R, Kokocinski F, Kulesha E, Lawson D, Longden I, Megy K, Meidl P, Overduin B, Parker A, Pritchard B, Rios D, Schuster M, Slater G, Smedley D, Spooner W, Spudich G, Trevanion S, Vilella A, Vogel J, White S, Wilder S, Zadissa A, Birney E, Cunningham F, Curwen V, Durbin R, Fernandez-Suarez XM, Herrero J, Kasprzyk A, Proctor G, Smith J, Searle S, Flicek P (2009) Ensembl 2009. Nucleic Acids Res 37:D690CrossRefPubMedGoogle Scholar
  24. Hur S, Stroud RM (2007) How U38, 39, and 40 of many tRNAs become the targets for pseudouridylation by TruA. Mol Cell 26:189CrossRefPubMedPubMedCentralGoogle Scholar
  25. Jana S, Hsieh AC, Gupta R (2017) Reciprocal amplification of caspase-3 activity by nuclear export of a putative human RNA-modifying protein, PUS10 during TRAIL-induced apoptosis. Cell Death Dis 8:e3093CrossRefPubMedPubMedCentralGoogle Scholar
  26. Jiang W, Middelton K, Yoon H-J, Fouquet C, Carbon J (1993) An essential yeast protein, CBF5p, binds in vitro to centromeres and microtubules. Mol Cell Biol 13:4884CrossRefPubMedPubMedCentralGoogle Scholar
  27. Joardar A, Jana S, Fitzek E, Gurha P, Majumder M, Chatterjee K, Geisler M, Gupta R (2013) Role of forefinger and thumb loops in production of 54 and 55 in tRNAs by archaeal Pus10. RNA 19:1279CrossRefPubMedPubMedCentralGoogle Scholar
  28. Kamalampeta R, Keffer-Wilkes LC, Kothe U (2013) tRNA binding, positioning, and modification by the pseudouridine synthase Pus10. J Mol Biol 425:3863CrossRefPubMedGoogle Scholar
  29. Kaya Y, Ofengand J (2003) A novel unanticipated type of pseudouridine synthase with homologs in bacteria, archaea, and eukarya. RNA 9:711CrossRefPubMedPubMedCentralGoogle Scholar
  30. Koonin EV (2010) The origin and early evolution of eukaryotes in the light of phylogenomics. Genome Biol 11:209CrossRefPubMedPubMedCentralGoogle Scholar
  31. Koonin EV, Wolf YI (2010) Constraints and plasticity in genome and molecular-phenome evolution. Nat Rev Genet 11:487CrossRefPubMedPubMedCentralGoogle Scholar
  32. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG (2007) Clustal W and clustal X version 2.0. Bioinformatics 23:2947CrossRefPubMedGoogle Scholar
  33. Letunic I, Bork P (2011) Interactive Tree Of Life v2: online annotation and display of phylogenetic trees made easy. Nucleic Acids Res 39:W475CrossRefPubMedPubMedCentralGoogle Scholar
  34. Letunic I, Bork P (2016) Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res 44:W242CrossRefPubMedPubMedCentralGoogle Scholar
  35. McCleverty CJ, Hornsby M, Spraggon G, Kreusch A (2007) Crystal structure of human Pus10, A novel pseudouridine synthase. J Mol Biol 373:1243CrossRefPubMedGoogle Scholar
  36. McGinnis S, Madden TL (2004) BLAST: at the core of a powerful and diverse set of sequence analysis tools. Nucleic Acids Res 32:W20CrossRefPubMedPubMedCentralGoogle Scholar
  37. Mueller EG, Ferré-D’Amaré AR (2009) DNA and RNA modification enzymes. In: Grosjean H (ed) Pseudouridine formation the most common transglycosylation in RNA. Landes Bioscience, AustinGoogle Scholar
  38. Nordlund ME, Johansson JO, von Pawel-Rammingen U, Byström AS (2000) Identification of the TRM2 gene encoding the tRNA(m5U54)methyltransferase of Saccharomyces cerevisiae. RNA 6:844CrossRefPubMedPubMedCentralGoogle Scholar
  39. Nurse K, Wrzesinski J, Bakin A, Lane BG, Ofengand J (1995) Purification, cloning, and properties of the tRNA Ψ55 synthase from Escherichia coli. RNA 1:102PubMedPubMedCentralGoogle Scholar
  40. Ny T, Björk GR (1980) Cloning and restriction mapping of the trmA gene coding for transfer ribonucleic acid (5-methyluridine)-methyltransferase in Escherichia coli K-12. J Bacteriol 142:371PubMedPubMedCentralGoogle Scholar
  41. Pan H, Agarwalla S, Moustakas DT, Finer-Moore J, Stroud RM (2003) Structure of tRNA pseudouridine synthase TruB and its RNA complex: RNA recognition through a combination of rigid docking and induced fit. Proc Natl Acad Sci 100:12648CrossRefPubMedPubMedCentralGoogle Scholar
  42. Park S-Y, Shin JN, Woo HN, Piya S, Moon AR, Seo Y-W, Seol D-W, Kim T-H (2009) DOBI is cleaved by caspases during TRAIL-induced apoptotic cell death. BMB Rep 42:511CrossRefPubMedGoogle Scholar
  43. Proost S, Pattyn P, Gerats T, Van de Peer Y (2011) Journey through the past: 150 million years of plant genome evolution. Plant J 66:58CrossRefPubMedGoogle Scholar
  44. Rashid R, Liang B, Baker DL, Youssef OA, He Y, Phipps K, Terns RM, Terns MP, Li H (2006) Crystal structure of a Cbf5-Nop10-Gar1 complex and implications in RNA-guided pseudouridylation and dyskeratosis congenita. Mol Cell 21:249CrossRefPubMedGoogle Scholar
  45. Roe B, Tsen H-Y (1977) Role of ribothymidine in mammalian tRNAPhe. Proc Natl Acad Sci 74:3696CrossRefPubMedPubMedCentralGoogle Scholar
  46. Roovers M, Hale C, Tricot C, Terns MP, Terns RM, Grosjean H, Droogmans L (2006) Formation of the conserved pseudouridine at position 55 in archaeal tRNA. Nucleic Acids Res 34:4293CrossRefPubMedPubMedCentralGoogle Scholar
  47. Sémon M, Wolfe KH (2007) Consequences of genome duplication. Curr Opin Genet Dev 17:505CrossRefPubMedGoogle Scholar
  48. Sivaraman J, Sauvé V, Larocque R, Stura EA, Schrag JD, Cygler M, Matte A (2002) Structure of the 16S rRNA pseudouridine synthase RsuA bound to uracil and UMP. Nat Struct Biol 9:353PubMedGoogle Scholar
  49. Spedaliere CJ, Hamilton CS, Mueller EG (2000) Functional Importance of Motif I of pseudouridine synthases: mutagenesis of aligned lysine and proline residues. Biochemistry 39:9459CrossRefPubMedGoogle Scholar
  50. Stamatakis A (2006) RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics 22:2688CrossRefPubMedGoogle Scholar
  51. Thomas BC, Pedersen B, Freeling M (2006) Following tetraploidy in an Arabidopsis ancestor, genes were removed preferentially from one homeolog leaving clusters enriched in dose-sensitive genes. Genome Res 16:934CrossRefPubMedPubMedCentralGoogle Scholar
  52. Urbonavičius J, Auxilien S, Walbott H, Trachana K, Golinelli-Pimpaneau B, Brochier-Armanet C, Grosjean H (2008) Acquisition of a bacterial RumA-type tRNA(uracil-54, C5)-methyltransferase by Archaea through an ancient horizontal gene transfer. Mol Microbiol 67:323CrossRefPubMedGoogle Scholar
  53. Vercammen D (2004) Type II metacaspases Atmc4 and Atmc9 of Arabidopsis thaliana cleave substrates after arginine and lysine. J Biol Chem 279:45329CrossRefPubMedGoogle Scholar
  54. Vercammen D, Declercq W, Vandenabeele P, Van Breusegem F (2007) Are metacaspases caspases? J Cell Biol 179:375CrossRefPubMedPubMedCentralGoogle Scholar
  55. Whelan S, Goldman N (2001) A general empirical model of protein evolution derived from multiple protein families using a maximum-likelihood approach. Mol Biol Evol 18:691CrossRefPubMedGoogle Scholar
  56. Yu F, Liu X, Alsheikh M, Park S, Rodermel S (2008) Mutations in SUPPRESSOR OF VARIEGATION1, a factor required for normal chloroplast translation, suppress var2-mediated leaf variegation in Arabidopsis. Plant Cell Online 20:1786CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Plant BiologySouthern Illinois UniversityCarbondaleUSA
  2. 2.Department of Biochemistry and Molecular BiologySouthern Illinois UniversityCarbondaleUSA
  3. 3.Department of Biological SciencesNorthern Illinois UniversityDekalbUSA
  4. 4.Molecular and Cellular BiologyUniversity of ArizonaTucsonUSA

Personalised recommendations