Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Utilization of selenocysteine in early-branching fungal phyla

Abstract

Selenoproteins are a diverse group of proteins containing selenocysteine (Sec)—the twenty-first amino acid—incorporated during translation via a unique recoding mechanism1,2. Selenoproteins fulfil essential roles in many organisms1, yet are not ubiquitous across the tree of life3,4,5,6,7. In particular, fungi were deemed devoid of selenoproteins4,5,8. However, we show here that Sec is utilized by nine species belonging to diverse early-branching fungal phyla, as evidenced by the genomic presence of both Sec machinery and selenoproteins. Most fungal selenoproteins lack consensus Sec recoding signals (SECIS elements9) but exhibit other RNA structures, suggesting altered mechanisms of Sec insertion in fungi. Phylogenetic analyses support a scenario of vertical inheritance of the Sec trait within eukaryotes and fungi. Sec was then lost in numerous independent events in various fungal lineages. Notably, Sec was lost at the base of Dikarya, resulting in the absence of selenoproteins in Saccharomyces cerevisiae and other well-studied fungi. Our results indicate that, despite scattered occurrence, selenoproteins are found in all kingdoms of life.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Sec machinery genes in fungal genome assemblies.
Fig. 2: Selenoproteins and Sec machinery in Sec-utilizing fungi.
Fig. 3: Reconstructed phylogenetic tree of SPS proteins.

Similar content being viewed by others

Code availability

The latest version of the selenoprotein gene finder software Selenoprofiles is available at https://github.com/marco-mariotti/selenoprofiles. The script ncbi_assembly, used to download NCBI assemblies in batch, is available at https://github.com/marco-mariotti/ncbi_db.

Data availability

A list of the fungal species and corresponding genomes (NCBI assembly accession IDs) used in this study is provided in Supplementary Table 1. Supplementary Data 1 contains the sequences of all of the genes and RNA elements mentioned in this work, as well as their genomic coordinates to derive these sequences from genomes. For each species, coordinates are mapped to GenBank nucleotide entries (contigs or scaffolds) found within their corresponding genome. Our re-annotated open reading frames are in the process of being assigned GenBank IDs.

References

  1. Labunskyy, V. M., Hatfield, D. L. & Gladyshev, V. N. Selenoproteins: molecular pathways and physiological roles. Physiol. Rev. 94, 739–777 (2014).

    Article  CAS  Google Scholar 

  2. Xu, X. M. et al. Biosynthesis of selenocysteine on its tRNA in eukaryotes. PLoS Biol. 5, e4 (2007).

    Article  Google Scholar 

  3. Zhang, Y., Romero, H., Salinas, G. & Gladyshev, V. Dynamic evolution of selenocysteine utilization in bacteria: a balance between selenoprotein loss and evolution of selenocysteine from redox active cysteine residues. Genome Biol. 7, R94 (2006).

    Article  Google Scholar 

  4. Mariotti, M. et al. Evolution of selenophosphate synthetases: emergence and relocation of function through independent duplications and recurrent subfunctionalization. Genome Res. 25, 1256–1267 (2015).

    Article  CAS  Google Scholar 

  5. Lobanov, A. V., Hatfield, D. L. & Gladyshev, V. N. Eukaryotic selenoproteins and selenoproteomes. Biochim. Biophys. Acta 1790, 1424–1428 (2009).

    Article  CAS  Google Scholar 

  6. Chapple, C. E. & Guigó, R. Relaxation of selective constraints causes independent selenoprotein extinction in insect genomes.PLoS ONE 13, e2968 (2008).

    Article  Google Scholar 

  7. Otero, L. et al. Adjustments, extinction, and remains of selenocysteine incorporation machinery in the nematode lineage. RNA 20, 1023–1034 (2014).

    Article  CAS  Google Scholar 

  8. Jiang, L. et al. Evolution of selenoproteins in the metazoan. BMC Genomics 13, 446 (2012).

    Article  CAS  Google Scholar 

  9. Krol, A. Evolutionarily different RNA motifs and RNA–protein complexes to achieve selenoprotein synthesis. Biochimie 84, 765–774 (2002).

    Article  CAS  Google Scholar 

  10. Gupta, N., DeMong, L. W., Banda, S. & Copeland, P. R. Reconstitution of selenocysteine incorporation reveals intrinsic regulation by SECIS elements. J. Mol. Biol. 425, 2415–2422 (2013).

    Article  CAS  Google Scholar 

  11. Castellano, S. et al. Low exchangeability of selenocysteine, the 21st amino acid, in vertebrate proteins. Mol. Biol. Evol. 26, 2031–2040 (2009).

    Article  CAS  Google Scholar 

  12. Reich, H. J. & Hondal, R. J. Why nature chose selenium. ACS Chem. Biol. 11, 821–841 (2016).

    Article  CAS  Google Scholar 

  13. Lin, J. et al. Comparative genomics reveals new candidate genes involved in selenium metabolism in prokaryotes. Genome Biol. Evol. 7, 664–676 (2015).

    Article  CAS  Google Scholar 

  14. Mariotti, M. et al. Lokiarchaeota marks the transition between the archaeal and eukaryotic selenocysteine encoding systems. Mol. Biol. Evol. 33, 2441–2453 (2016).

    Article  CAS  Google Scholar 

  15. Mariotti, M. et al. Composition and evolution of the vertebrate and mammalian selenoproteomes. PLoS ONE 7, e33066 (2012).

    Article  CAS  Google Scholar 

  16. Lobanov, A. V. et al. Evolutionary dynamics of eukaryotic selenoproteomes: large selenoproteomes may associate with aquatic life and small with terrestrial life. Genome Biol. 8, R198 (2007).

    Article  Google Scholar 

  17. Mariotti, M. & Guigó, R. Selenoprofiles: profile-based scanning of eukaryotic genome sequences for selenoprotein genes. Bioinformatics 26, 2656–2663 (2010).

    Article  CAS  Google Scholar 

  18. Santesmasses, D., Mariotti, M. & Guigó, R. Computational identification of the selenocysteine tRNA (tRNASec) in genomes. PLoS Comput. Biol. 13, e1005383 (2017).

    Article  Google Scholar 

  19. Cox, A. G. et al. Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis. Proc. Natl Acad. Sci. USA 113, E5562–E5571 (2016).

    Article  CAS  Google Scholar 

  20. Castellano, S. et al. Reconsidering the evolution of eukaryotic selenoproteins: a novel nonmammalian family with scattered phylogenetic distribution. EMBO Rep. 5, 71–77 (2004).

    Article  CAS  Google Scholar 

  21. Mariotti, M., Lobanov, A. V., Guigo, R. & Gladyshev, V. N. SECISearch3 and Seblastian: new tools for prediction of SECIS elements and selenoproteins. Nucleic Acids Res. 41, e149 (2013).

    Article  CAS  Google Scholar 

  22. Lee, B. C., Dikiy, A., Kim, H.-Y. & Gladyshev, V. N. Functions and evolution of selenoprotein methionine sulfoxide reductases. Biochim. Biophys. Acta 1790, 1471–1477 (2009).

    Article  CAS  Google Scholar 

  23. Darras, V. M. & Van Herck, S. L. J. Iodothyronine deiodinase structure and function: from ascidians to humans. J. Endocrinol. 215, 189–206 (2012).

    Article  CAS  Google Scholar 

  24. Arnér, E. S. & Holmgren, A. Physiological functions of thioredoxin and thioredoxin reductase. Eur. J. Biochem. 267, 6102–6109 (2000).

    Article  Google Scholar 

  25. Gruber, A. R., Findeiß, S., Washietl, S., Hofacker, I. L. & Stadler, P. F. RNAz 2.0: improved noncoding RNA detection.Pac. Symp. Biocomput. 15, 69–79 (2010).

    Google Scholar 

  26. Lorenz, R. et al. ViennaRNA package 2.0. Algorithms Mol. Biol. 6, 26 (2011).

    Article  Google Scholar 

  27. Pellegrini, M., Marcotte, E. M., Thompson, M. J., Eisenberg, D. & Yeates, T. O. Assigning protein functions by comparative genome analysis: protein phylogenetic profiles. Proc. Natl Acad. Sci. USA 96, 4285–4288 (1999).

    Article  CAS  Google Scholar 

  28. Spatafora, J. W. et al. A phylum-level phylogenetic classification of zygomycete fungi based on genome-scale data. Mycologia 108, 1028–1046 (2016).

    Article  CAS  Google Scholar 

  29. Howard, M. T. et al. Recoding elements located adjacent to a subset of eukaryal selenocysteine-specifying UGA codons. EMBO J. 24, 1596–1607 (2005).

    Article  CAS  Google Scholar 

  30. Labunskyy, V. M. et al. The insertion Green Monster (iGM) method for expression of multiple exogenous genes in yeast. G3 (Bethesda) 4, 1183–1191 (2014).

    Article  CAS  Google Scholar 

  31. Slater, G. S. C. & Birney, E. Automated generation of heuristics for biological sequence comparison. BMC Bioinformatics 6, 31 (2005).

    Article  Google Scholar 

  32. Birney, E., Clamp, M. & Durbin, R. GeneWise and Genomewise. Genome Res. 14, 988–995 (2004).

    Article  CAS  Google Scholar 

  33. Gladyshev, V. N. in Selenium 127–139 (Springer International Publishing, New York, 2016).

  34. Zhang, Y. in Selenium 141–150 (Springer International Publishing, New York, 2016).

  35. Camacho, C. et al. BLAST+: architecture and applications. BMC Bioinformatics 10, 421 (2009).

    Article  Google Scholar 

  36. NCBI Resource Coordinators. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. 45, D12–D17 (2017).

    Article  Google Scholar 

  37. Katoh, K. & Standley, D. M. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol. Biol. Evol. 30, 772–780 (2013).

    Article  CAS  Google Scholar 

  38. Capella-Gutiérrez, S., Silla-Martínez, J. M. & Gabaldón, T. trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics 25, 1972–1973 (2009).

    Article  Google Scholar 

  39. Huerta-Cepas, J., Serra, F. & Bork, P. ETE 3: reconstruction, analysis, and visualization of phylogenomic data. Mol. Biol. Evol. 33, 1635–1638 (2016).

    Article  CAS  Google Scholar 

  40. Huerta-Cepas, J., Capella-Gutiérrez, S., Pryszcz, L. P., Marcet-Houben, M. & Gabaldón, T. PhylomeDB v4: zooming into the plurality of evolutionary histories of a genome. Nucleic Acids Res. 42, D897–D902 (2014).

    Article  CAS  Google Scholar 

  41. Wallace, I. M., O’Sullivan, O., Higgins, D. G. & Notredame, C. M-Coffee: combining multiple sequence alignment methods with T-Coffee. Nucleic Acids Res. 34, 1692–1699 (2006).

    Article  CAS  Google Scholar 

  42. Guindon, S. et al. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst. Biol. 59, 307–321 (2010).

    Article  CAS  Google Scholar 

  43. Wang, Y. et al. Comparative genomics reveals the core gene toolbox for the fungus–insect symbiosis.mBio 9, e00636-18 (2018).

    Article  Google Scholar 

  44. Nawrocki, E. P., Kolbe, D. L. & Eddy, S. R. Infernal 1.0: inference of RNA alignments. Bioinformatics 25, 1335–1337 (2009).

    Article  CAS  Google Scholar 

  45. Sievers, F. et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539 (2011).

    Article  Google Scholar 

  46. Waterhouse, A. M., Procter, J. B., Martin, D. M. A., Clamp, M. & Barton, G. J. Jalview Version 2—a multiple sequence alignment editor and analysis workbench. Bioinformatics 25, 1189–1191 (2009).

    Article  CAS  Google Scholar 

  47. Griffiths-Jones, S. RALEE—RNA alignment editor in Emacs. Bioinformatics 21, 257–259 (2005).

    Article  CAS  Google Scholar 

  48. Waterhouse, R. M. et al. BUSCO applications from quality assessments to gene prediction and phylogenomics. Mol. Biol. Evol. 35, 543–548 (2017).

    Article  Google Scholar 

  49. Nordberg, H. et al. The genome portal of the Department of Energy Joint Genome Institute: 2014 updates. Nucleic Acids Res. 42, D26–D31 (2014).

    Article  CAS  Google Scholar 

  50. Laslett, D. & Canback, B. ARAGORN, a program to detect tRNA genes and tmRNA genes in nucleotide sequences. Nucleic Acids Res. 32, 11–16 (2004).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by National Institutes of Health grants DK117149, AG021518 and CA080946. Funding for the open access charge was provided by the National Institutes of Health.

Author information

Authors and Affiliations

Authors

Contributions

G.S. first noted Sec machinery in a fungal genome and initiated this study. M.M. designed and performed the data analyses and wrote the manuscript. G.S., T.G. and V.N.G. participated in critical discussion and revised the manuscript.

Corresponding authors

Correspondence to Marco Mariotti or Vadim N. Gladyshev.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Figures 1–26 and Supplementary Notes.

Reporting Summary

Supplementary Table 1

Species names, assembly identifiers and taxonomic annotation of all fungal genomes analysed in this study.

Supplementary Table 2

Results of phylogenetic profiling to detect proteins related to Sec.

Supplementary Data 1 and 2

Sequences and genomic coordinates of Sec machinery, selenoproteins and RNA structures described in this work, and reconstructed phylogenetic trees of Sec machinery and selenoproteins (the same as in Fig. 3 and in Supplementary Figures 2–10) with branch support values.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mariotti, M., Salinas, G., Gabaldón, T. et al. Utilization of selenocysteine in early-branching fungal phyla. Nat Microbiol 4, 759–765 (2019). https://doi.org/10.1038/s41564-018-0354-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41564-018-0354-9

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing