Skip to main content
SpringerLink
Log in

The functional study of human proteins using humanized yeast

  • Minireview
  • Published:
Journal of Microbiology Aims and scope Submit manuscript

Abstract

The functional and optimal expression of genes is crucial for survival of all living organisms. Numerous experiments and efforts have been performed to reveal the mechanisms required for the functional and optimal expression of human genes. The yeast Saccharomyces cerevisiae has evolved independently of humans for billions of years. Nevertheless, S. cerevisiae has many conserved genes and expression mechanisms that are similar to those in humans. Yeast is the most commonly used model organism for studying the function and expression mechanisms of human genes because it has a relatively simple genome structure, which is easy to manipulate. Many previous studies have focused on understanding the functions and mechanisms of human proteins using orthologous genes and biological systems of yeast. In this review, we mainly introduce two recent studies that replaced human genes and nucleosomes with those of yeast. Here, we suggest that, although yeast is a relatively small eukaryotic cell, its humanization is useful for the direct study of human proteins. In addition, yeast can be used as a model organism in a broader range of studies, including drug screening.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ben Yehuda, S., Dix, I., Russell, C.S., Levy, S., Beggs, J.D., and Ku-piec, M. 1998. Identification and functional analysis of hPRP17, the human homologue of the PRP17/CDC40 yeast gene involved in splicing and cell cycle control. RNA4, 1304–1312.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boger-Nadjar, E., Vaisman, N., Ben-Yehuda, S., Kassir, Y., and Ku-piec, M. 1998. Efficient initiation of S-phase in yeast requires Cdc40p, a protein involved in pre-mRNA splicing. Mol. Gen. Genet.260, 232–241.

    Article  CAS  PubMed  Google Scholar 

  • Byrne, K.P. and Wolfe, K.H. 2005. The yeast gene order browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res.15, 1456–1461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, X. and Zhang, J. 2012. The ortholog conjecture is untestable by the current gene ontology but is supported by RNA sequencing data. PLoS Comput. Biol.8, e1002784.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Embley, T.M. and Martin, W. 2006. Eukaryotic evolution, changes and challenges. Nature440, 623–630.

    Article  CAS  PubMed  Google Scholar 

  • Eriksson, P.R., Ganguli, D., Nagarajavel, V., and Clark, D.J. 2012. Regulation of histone gene expression in budding yeast. Genetics191, 7–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frost, A., Elgort, M.G., Brandman, O., Ives, C., Collins, S.R., Miller-Vedam, L., Weibezahn, J., Hein, M.Y., Poser, I., Mann, M., et al. 2012. Functional repurposing revealed by comparing S. pombe and S. cerevisiae genetic interactions. Cell149, 1339–1352.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gabaldon, T. and Koonin, E.V. 2013. Functional and evolutionary implications of gene orthology. Nat. Rev. Genet.14, 360–366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hardy, J. and Selkoe, D.J. 2002. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science297, 353–356.

    Article  CAS  PubMed  Google Scholar 

  • Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Ham-shere, M.L., Pahwa, J.S., Moskvina, V., Dowzell, K., Williams, A., et al. 2009. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat. Genet.41, 1088–1093.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Howman, E.V., Fowler, K.J., Newson, A.J., Redward, S., MacDonald, A.C., Kalitsis, P., and Choo, K.H. 2000. Early disruption of centromeric chromatin organization in centromere protein A (Cenpa) null mice. Proc. Natl. Acad. Sci. USA97, 1148–1153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kachroo, A.H., Laurent, J.M., Yellman, C.M., Meyer, A.G., Wilke, C.O., and Marcotte, E.M. 2015. Evolution. Systematic humani-zation of yeast genes reveals conserved functions and genetic modularity. Science348, 921–925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kataoka, T., Powers, S., Cameron, S., Fasano, O., Goldfarb, M., Broach, J., and Wigler, M. 1985. Functional homology of mammalian and yeast RAS genes. Cell40, 19–26.

    Article  CAS  PubMed  Google Scholar 

  • Koonin, E.V. 2005. Orthologs, paralogs, and evolutionary genomics. Annu. Rev. Genet.39, 309–338.

    Article  CAS  PubMed  Google Scholar 

  • Kupfer, D.M., Drabenstot, S.D., Buchanan, K.L., Lai, H., Zhu, H., Dyer, D.W., Roe, B.A., and Murphy, J.W. 2004. Introns and splicing elements of five diverse fungi. Eukaryot. Cell3, 1088–1100.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lambert, J.C., Heath, S., Even, G., Campion, D., Sleegers, K., Hiltunen, M., Combarros, O., Zelenika, D., Bullido, M.J., Tavernier, B., et al. 2009. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat. Genet.41, 1094–1099.

    Article  CAS  PubMed  Google Scholar 

  • Lander, E.S., Linton, L.M., Birren, B., Nusbaum, C., Zody, M.C., Baldwin, J., Devon, K., Dewar, K., Doyle, M., FitzHugh, W., et al. 2001. Initial sequencing and analysis of the human genome. Nature409, 860–921.

    Article  CAS  PubMed  Google Scholar 

  • Laurent, J.M., Young, J.H., Kachroo, A.H., and Marcotte, E.M. 2016. Efforts to make and apply humanized yeast. Brief. Funct. Geno-mics15, 155–163.

    Article  CAS  Google Scholar 

  • Lee, S.W. and Oh, M.K. 2015. A synthetic suicide riboswitch for the high-throughput screening of metabolite production in Saccha-romyces cerevisiae. Metab. Eng.28, 143–150.

    Article  CAS  PubMed  Google Scholar 

  • Lowary, P.T. and Widom, J. 1998. New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning. J. Mol. Biol.276, 19–42.

    Article  CAS  PubMed  Google Scholar 

  • McBurney, K.L., Leung, A., Choi, J.K., Martin, B.J., Irwin, N.A., Bartke, T., Nelson, C.J., and Howe, L.J. 2016. Divergent residues within histone H3 dictate a unique chromatin structure in Sac-charomyces cerevisiae. Genetics202, 341–349.

    Article  CAS  PubMed  Google Scholar 

  • Nash, R.S., Volpe, T., and Futcher, B. 2001. Isolation and characterization of WHI3, a size-control gene of Saccharomyces cerevisiae. Genetics157, 1469–1480.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nehrt, N.L., Clark, W.T., Radivojac, P., and Hahn, M.W. 2011. Testing the ortholog conjecture with comparative functional genomic data from mammals. PLoS Comput. Biol.7, e1002073.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Osborn, M.J. and Miller, J.R. 2007. Rescuing yeast mutants with human genes. Brief. Funct. Genomic Proteomic6, 104–111.

    Article  CAS  PubMed  Google Scholar 

  • Pausch, M.H. 1997. G-protein-coupled receptors in Saccharomyces cerevisiae: high-throughput screening assays for drug discovery. Trends Biotechnol.15, 487–494.

    Article  CAS  PubMed  Google Scholar 

  • Rando, O.J. and Winston, F. 2012. Chromatin and transcription in yeast. Genetics190, 351–387.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ryan, C.J., Roguev, A., Patrick, K., Xu, J., Jahari, H., Tong, Z., Beltrao, P., Shales, M., Qu, H., Collins, S.R., et al. 2012. Hierarchical modularity and the evolution of genetic interactomes across species. Mol. Cell46, 691–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Segal, E. and Widom, J. 2009. What controls nucleosome positions? Trends Genet.25, 335–343.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sogin, M.L. 1991. Early evolution and the origin of eukaryotes. Curr. Opin. Genet. Dev.1, 457–463.

    Article  CAS  PubMed  Google Scholar 

  • Sonnhammer, E.L. and Koonin, E.V. 2002. Orthology, paralogy and proposed classification for paralog subtypes. Trends Genet.18, 619–620.

    Article  CAS  PubMed  Google Scholar 

  • Stoler, S., Keith, K.C., Curnick, K.E., and Fitzgerald-Hayes, M. 1995. A mutation in CSE4, an essential gene encoding a novel chro-matin-associated protein in yeast, causes chromosome nondis-junction and cell cycle arrest at mitosis. Genes Dev.9, 573–586.

    Article  CAS  PubMed  Google Scholar 

  • Theissen, G. 2002. Secret life of genes. Nature415, 741.

    Article  PubMed  Google Scholar 

  • Tong, A.H., Evangelista, M., Parsons, A.B., Xu, H., Bader, G.D., Pagé, N., Robinson, M., Raghibizadeh, S., Hogue, C.W., Bussey, H., et al. 2001. Systematic genetic analysis with ordered arrays of yeast deletion mutants. Science294, 2364–2368.

    Article  CAS  PubMed  Google Scholar 

  • Treusch, S., Hamamichi, S., Goodman, J.L., Matlack, K.E., Chung, C.Y., Baru, V., Shulman, J.M., Parrado, A., Bevis, B.J., Valastyan, J.S., et al. 2011. Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer’s disease risk factors in yeast. Science334, 1241–1245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Truong, D.M. and Boeke, J.D. 2017. Resetting the yeast epigenome with human nucleosomes. Cell171, 1508–1519.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tugendreich, S., Perkins, E., Couto, J., Barthmaier, P., Sun, D., Tang, S., Tulac, S., Nguyen, A., Yeh, E., Mays, A., et al. 2001. A streamlined process to phenotypically profile heterologous cDNAs in parallel using yeast cell-based assays. Genome Res.11, 1899–1912.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Velours, J., Vaillier, J., Paumard, P., Soubannier, V., Lai-Zhang, J., and Mueller, D.M. 2001. Bovine coupling factor 6, with just 14.5% shared identity, replaces subunit h in the yeast ATP syn-thase. J. Biol. Chem.276, 8602–8607.

    Article  CAS  PubMed  Google Scholar 

  • Wang, X., Dalkic, E., Wu, M., and Chan, C. 2008. Gene module level analysis: Identification to networks and dynamics. Curr. Opin. Biotechnol.19, 482–491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • White, C.L., Suto, R.K., and Luger, K.B. 2001. Structure of the yeast nucleosome core particle reveals fundamental changes in inter-nucleosome interactions. EMBO J.20, 5207–5218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wieland, G., Orthaus, S., Ohndorf, S., Diekmann, S., and Hemmerich, P. 2004. Functional complementation of human centromere protein A (CENP-A) by Cse4p from Saccharomyces cere-visiae. Mol. Cell. Biol.24, 6620–6630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, N., Osborn, M., Gitsham, P., Yen, K., Miller, J.R., and Oliver, S.G. 2003. Using yeast to place human genes in functional categories. Gene303, 121–129.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Research Foundation of Korea grants (No. NRF-2015R1A4A1041105, NRF-2015R1D1A1A02061743, NRF-2018R1D1A1A02048280, and NRF-2019R1G1A1100730), and Pusan National University Research Grant, 2019.

Author information

Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon, 24341, Republic of Korea

    Seho Kim, Juhee Park & Jung-Shin Lee

  2. Department of Biology Education, Pusan National University, Busan, 26241, Republic of Korea

    Taekyung Kim

Authors
  1. Seho Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juhee Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Taekyung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jung-Shin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Taekyung Kim or Jung-Shin Lee.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, S., Park, J., Kim, T. et al. The functional study of human proteins using humanized yeast. J Microbiol. 58, 343–349 (2020). https://doi.org/10.1007/s12275-020-0136-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12275-020-0136-y

Keywords

Search

Navigation