Abstract
Transmissible spongiform encephalopathies (TSEs) are currently incurable, always fatal, and have the potential to cross species boundaries. The expression of TSEs is thought to be influenced by genetic variation at the prion protein gene (PRNP). Although a wide range of mammals exhibit TSEs, it is currently unclear whether they are evolutionarily clustered or if TSE+ species are randomly distributed phylogenetically. We tested whether mammalian species with TSEs are phylogenetically underdispersed on three phylogenetic trees, one constructed from 20 aligned gene sequences for 102 taxa (a species tree), and PRNP gene trees from nucleotide and from amino acid sequence variation. TSEs were present in a variety of orders excluding Chiroptera, Eulipotyphyla, and Lagomorpha, and cetaceans. The occurrence of TSEs on the PRNP and species trees is non-random (Species tree D-value = 0.291; PRNP tree D-value = 0.273; PRNP amino acid tree D-value = 0.238), and TSEs appears to have arisen independently in the recent history of different mammalian groups. We found no evidence that particular protein motifs segregated between species with or without TSEs. Our findings suggest that the evolution of TSEs develops in groups of species irrespective of PRNP genotype.
Similar content being viewed by others
Availability of Data and Material
The datasets generated and/or analyzed during the current study are available in the Dryad repository, https://datadryad.org/stash/share/btwuVNlLidALaoreOtCIWbimNRphvOPAh0l5vLSfR8Q
Code Availability
All code and corresponding data used to produce presented results are available in the article and supplementary information files.
References
Acín C, Martín-Burriel I, Monleón E, Lyahyai J, Pitarch JL, Serrano C, Monzón M, Zaragoza P, Badiola JJ (2013) Prion protein gene variability in Spanish goats. Inference through susceptibility to classical scrapie strains and pathogenic distribution of peripheral PrPsc. PLoS ONE 8:e61118
Aguilar-Calvo P, Espinosa JC, Pintado B, Gutierrez-Adan A, Alamillo E, Miranda A, Prieto I, Bossers A, Andreoletti O, Torres JM, Caughey BW (2014) Role of the goat K222-PrPC polymorphic variant in prion infection resistance. J Virol 88:2670–2676
Aguilar-Calvo P, García C, Espinosa JC, Andreoletti O, Torres JM (2015) Prion and prion-like diseases in animals. Virus Res 207:82–93
Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L, Ren J, Li WW, Noble WS (2009) MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res 37:W202–W208
Bailey TL, Elkan C (1994) Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc Int Conf Intell Syst Mol Biol 2:28-36
Bailey TL, Gribskov M (1998) Combining evidence using p-values: application to sequence homology searches. Bioinformatics 14(1):48–54
Bouckaert R, Heled J, Kühnert D, Vaughan T, Wu C.-H, Xie D, Suchard MA, Rambaut A, Drummond AJ (2014) BEAST 2: a software platform for Bayesian evolutionary analysis. PLoS Comput Biol 10:1–6
Burbrink FT, Lorch JM, Lips KR (2017) Host susceptibility to snake fungal disease is highly dispersed across phylogenetic and functional trait space. Sci Adv 3:e1701387
Castresana J (2000) Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol Biol Evol 17:540–552
Cavender-Bares J, Kozak KH, Fine PVA, Kembel SW (2009) The merging of community ecology and phylogenetic biology. Ecol Lett 12:693–715
Collinge J, Clarke AR (2007) A general model of prion strains and their pathogenicity. Science 318:930–936
Collinge J, Whittington MA, Sidle KCL, Smith CJ, Palmer MS, Clarke AR, Jefferys JGR (1994) Prion protein is necessary for normal synaptic function. Nature 370:295–297
Cullingham CI, Peery RM, Dao A, McKenzie DI, Coltman DW (2020) Predicting the spread-risk potential of chronic wasting disease to sympatric ungulate species. Prion 14(1):56-66
Dinkel H, Michael S, Weatheritt RJ, Davey NE, Van Roey K, Altenberg B, Toedt G, Uyar B, Seiler M, Budd A, Jödicke L, Dammert MA, Schroeter C, Hammer M, Schmidt T, Jehl P, McGuigan C, Dymecka M, Chica C, Luck K, Via A, Chatr-Aryamontri A, Haslam N, Grebnev G, Edwards RJ, Steinmetz MO, Meiselbach H, Diella F, Gibson TJ (2011) ELM--the database of eukaryotic linear motifs. Nucleic Acids Res 40(D1), D242–D251
Drummond AJ, Rambaut A (2007) BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 7(1):214
Eilebrecht S, Hotz-Wagenblatt A, Sarachaga V, Burk A, Falida K, Chakraborty D, Nikitina E, Tessmer C, Whitley C, Sauerland C, Gunst K, Grewe I, Bund T (2018) Expression and replication of virus-like circular DNA in human cells. Sci Rep 8:1-15
Esselstyn JA, Oliveros CH, Swanson MT, Faircloth BC (2017) Investigating difficult nodes in the placental mammal tree with expanded taxon sampling and thousands of ultraconserved elements. Genome Biol Evol 9:2308–2321
Fernández-Borges N, Chianini F, Eraña H, Vidal E, Eaton SL, Pintado B, Finlayson J, Dagleish MP, Castilla J (2012) Naturally prion resistant mammals. Prion 6:425–429
Fritz SA, Purvis A (2010) Selectivity in mammalian extinction risk and threat types: a new measure of phylogenetic signal strength in binary traits: selectivity in extinction risk. Conserv Biol 24:1042–1051
Goldfarb LG, Brown P, McCombie WR, Goldgaber D, Swergold GD, Wills PR, Cervenakova L, Baron H, Gibbs CJ, Gajdusek DC (1991) Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene. Proc Natl Acad Sci USA 88:10926–10930
Gupta S, Stamatoyannopoulos JA, Bailey TL, Noble W (2007) Quantifying similarity between motifs. Genome Biol 8:R24
Hagenaars TJ, Melchior MB, Windig JJ, Bossers A, Davidse A, van Zijderveld FG (2018) Modelling of strategies for genetic control of scrapie in sheep: the importance of population structure. PLoS ONE 13:e0195009
Harrison PM, Khachane A, Kumar M (2010) Genomic assessment of the evolution of the prion protein gene family in vertebrates. Genomics 95:268–277
Heckeberg NS, Erpenbeck D, Wörheide G, Rössner GE (2016) Systematic relationships of five newly sequenced cervid species. PeerJ 4:e2307
Hou F, Sun L, Zheng H, Skaug B, Jiang Q-X, Chen ZJ (2011) MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell 146:448–461
Huelsenbeck JP, Nielsen R, Bollback JP (2003) Stochastic mapping of morphological characters. Syst Biol 52:131–158
Imran M, Mahmood S (2011) An overview of animal prion diseases. Virology J 8:559
Johnson CJ, Herbst A, Duque-Velasquez C, Vanderloo JP, Bochsler P, Chappell R, McKenzie D (2011) Prion protein polymorphisms affect chronic wasting disease progression. PLoS ONE 6:e17450
Kumar S, Stecher G, Li M, Knyaz C, Tamura K (2018) MEGA X: molecular evolutionary genetics analysis across computing platforms. Mole Biol Evol 35:1547–1549
Liu L, Zhang J, Rheindt FE, Lei F, Qu Y, Wang Y, Zhang Y, Sullivan C, Nie W, Wang J, Yang F, Chen J, Edwards SV, Meng J, Wu S (2017) Genomic evidence reveals a radiation of placental mammals uninterrupted by the KPg boundary. Proc Natl Acad Sci USA 114:E7282–E7290
Mawdsley JR (2020) Phylogenetic patterns suggest broad susceptibility to chronic wasting disease across Cervidae. Wildl Soc Bull. doi: https://doi.org/10.1002/wsb.1059
Mead S, Shah P, Al-Dujaily H, Hummerich H, Mein CA, Alpers MP (2009) A novel protective prion protein variant that colocalizes with kuru exposure. N Engl J Med 361:2056-2065
Memon S, Li G, Xiong H, Wang L, Liu X, Yuan M, Deng W, Xi D (2018) Deletion / insertion polymorphisms of the prion protein gene (PRNP) in gayal (Bos frontalis). J Genet 97:1131–1138
Mouillet-Richard S (2000) Signal transduction through prion protein. Science 289:1925–1928
Murphy WJ, Pevzner PA, O’Brien SJ (2004) Mammalian phylogenomics comes of age. Trends Genet 20:631–639
Osterholm MT, Anderson CJ, Zabel MD, Scheftel JM, Moore KA, Appleby BS (2019) Chronic wasting disease in cervids: implications for prion transmission to humans and other animal species. MBio 10(4):e01091-19
Prasad AB, Allard MW, NISC Comparative Sequencing Program, Green ED (2008) Confirming the phylogeny of mammals by use of large comparative sequence data sets. Mol Biol Evol 25:1795–1808
R Core Team (2018) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/
Ranwez V, Delsuc F, Ranwez S, Belkhir K, Tilak M-K, Douzery EJ (2007) OrthoMaM: a database of orthologous genomic markers for placental mammal phylogenetics. BMC Evol Biol 7:241
Revell LJ (2012) phytools: an R package for phylogenetic comparative biology (and other things). Methods Ecol Evol 3:217–223
Robinson DF, Foulds LR (1981) Comparison of phylogenetic trees. Math Biosci 53:131–147
Romiguier J, Ranwez V, Delsuc F, Galtier N, Douzery EJP (2013) Less is more in mammalian phylogenomics: AT-rich genes minimize tree conflicts and unravel the root of placental mammals. Mol Biol Evol 30:2134–2144
Rongyan Z, Xianglong L, Lanhui L, Xiangyun L, Fujun F (2008) Evolution and differentiation of the prion protein gene (PRNP) among species. J Hered 99:647–652
Roucou X, LeBlanc AC (2005) Cellular prion protein neuroprotective function: implications in prion diseases. J Mol Med 83:3–11
Salzano G, Giachin G, Legname G (2019) Structural consequences of copper binding to the prion protein. Cells 8:770
Seabury CM, Honeycutt RL, Rooney AP, Halbert ND, Derr JN (2004) Prion protein gene (PRNP) variants and evidence for strong purifying selection in functionally important regions of bovine exon 3. Proc Natl Acad Sci USA 101:15142–15147
Seabury CM, Oldeschulte DL, Bhattarai EK, Legare D, Ferro PJ, Metz RP, Johnson CD, Lockwood MA, Nichols TA (2020) Accurate genomic predictions for chronic wasting disease in US white-tailed deer. G3-Genes Genom Genet 10:1433-1441
Sigurdson CJ (2008) A prion disease of cervids: chronic wasting disease. Vet Res 39:41
Sigurdson CJ, Nilsson KPR, Hornemann S, Heikenwalder M, Manco G, Schwarz P, Ott D, Rulicke T, Liberski PP, Julius C, Falsig J, Stitz L, Wuthrich K, Aguzzi A (2009) De novo generation of a transmissible spongiform encephalopathy by mouse transgenesis. Proc Natl Acad Sci USA 106:304–309
Slate J (2005) Molecular evolution of the sheep prion protein gene. Proc R Soc B: Biol Sci 272:2371–2377
Stevens DJ, Walter ED, Rodríguez A, Draper D, Davies P, Brown DR, Millhauser GL (2009) Early onset prion disease from octarepeat expansion correlates with copper binding properties. PLoS Pathogens 5:e1000390
Swofford DL (2020) PAUP*4.0a168 (Phylogenetic analysis using PAUP). https://paup.phylosolutions.com/ - accessed 17 September 2020
Szigeti‐Buck K, Manuelidis L (2019) Prokaryotic SPHINX replication sequences are conserved in mammalian brain and participate in neurodegeneration. J Cell Biochem 120:17687–17698
Tajima F (1989) Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123:585-595
Talavera G, Castresana J (2007) Improvement of phylogenies after removing divergent and ambiguously aligned blocks from protein sequence alignments. Syst Biol 56:564–577
Teferedegn EY, Yaman Y, Ün C (2020) Novel variations in native Ethiopian goat breeds pRnp gene and their potential effect on prion protein stability. Sci Rep 10(1):1-10
Vassallo N, Herms J (2003) Cellular prion protein function in copper homeostasis and redox signalling at the synapse: cellular prion protein function. J Neurochem 86:538–544
Vázquez-Miranda H, Zink RM (2020) Geographic distribution of chronic wasting disease resistant alleles in Nebraska, with comments on the evolution of resistance. J Fish Wildl Manag 11:46-55
Zink RM, Najar N, Vázquez-Miranda H, Buchanan BL, Loy D, Brodersen BW (2020) Geographic variation in the PRNP gene and its promoter, and their relationship to chronic wasting disease in North American deer. Prion 14:185-192
Acknowledgments
We thank H. Vázquez-Miranda for help in conceptualizing this project and advice on phylogenetic methods, along with C. Chizinski and J. Lusk for their insight and helpful comments.
Funding
The authors received no specific funding for this work.
Author information
Authors and Affiliations
Contributions
Conceptualization: Brittaney L. Buchanan & Robert M. Zink, Data Curation: Brittaney L. Buchanan, Formal Analysis: Brittaney L. Buchanan, Funding Acquisition: N/A, no funding, Investigation: Brittaney L. Buchanan, Methodology: Brittaney L. Buchanan & Robert M. Zink, Project Administration: Brittaney L. Buchanan & Robert M. Zink, Resources: Robert M. Zink, Software: Brittaney L. Buchanan, Supervision: Brittaney L. Buchanan & Robert M. Zink, Validation: Brittaney L. Buchanan, Visualization: Brittaney L. Buchanan, Writing-Original Draft Preparation: Brittaney L. Buchanan, Writing-Review & Editing: Brittaney L. Buchanan & Robert M. Zink
Corresponding author
Ethics declarations
Ethics Approval
This study contains no studies of human participants or animals performed by any of the authors. This article is also not in consideration for or published at any other journal.
Consent to Participate
This study contains no human participants
Consent for Publication
No materials or figures have been published elsewhere
Conflict of Interest
The authors declare that they have no known competing financial interests.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Buchanan, B.L., Zink, R.M. Evolution of Transmissible Spongiform Encephalopathies and the Prion Protein Gene (PRNP) in Mammals. J Mammal Evol 28, 573–582 (2021). https://doi.org/10.1007/s10914-021-09557-6
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10914-021-09557-6