Skip to main content

Telomere Length is a Susceptibility Marker for Tasmanian Devil Facial Tumor Disease

EcoHealth volume 17, pages 280–291 (2020)Cite this article

Abstract

Telomeres protect chromosomes from degradation during cellular replication. In humans, it is well-documented that excessive telomere degradation is one mechanism by which cells can become cancerous. Increasing evidence from wildlife studies suggests that telomere length is positively correlated with survival and health and negatively correlated with disease infection intensity. The recently emerged devil facial tumor disease (DFTD) has led to dramatic and rapid population declines of the Tasmanian devil throughout its geographic range. Here, we tested the hypothesis that susceptibility to DFTD is negatively correlated with telomere length in devils across three populations with different infection histories. Our findings suggest telomere length is correlated with DFTD resistance in three ways. First, devils from a population with the slowest recorded increase in DFTD prevalence (West Pencil Pine) have significantly longer telomeres than those from two populations with rapid and exponential increases in prevalence (Freycinet and Narawantapu). Second, using extensive mark-recapture data obtained from a long-term demographic study, we found that individuals with relatively long telomeres tend to be infected at a significantly later age than those with shorter telomeres. Third, a hazard model showed devils with longer telomeres tended to become infected at a lower rate than those with shorter telomeres. This research provides a rare study of telomere length variation and its association with disease in a wildlife population. Our results suggest that telomere length may be a reliable marker of susceptibility to DFTD and assist with future management of this endangered species.

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

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

References

  • Angelier F, Vleck CM, Holberton RL, Marra PP (2013) Telomere length, non-breeding habitat and return rate in male American redstarts. Functional Ecology 27: 342–350

    Google Scholar 

  • Asghar M, Hasselquist D, Hansson B, Zehtindjiev P, Westerdahl H, Bensch S (2015) Chronic infection. Hidden costs of infection: chronic malaria accelerates telomere degradation and senescence in wild birds. Science 347: 436–8

    CAS  PubMed  Google Scholar 

  • Barton K (2016) MuMIn: Multi-Model Inference. R package version 1.15.6. URL https://CRAN.R-project.org/package=MuMIn

  • Beirne C, Delahay R, Hares M, Young A (2014) Age-related declines and disease-associated variation in immune cell telomere length in a wild mammal. PLoS One 9: e108964.

    PubMed  PubMed Central  Google Scholar 

  • Bender HS, Murchison EP, Pickett HA, Deakin JE, Strong MA, Conlan C, McMillan DA, Neumann AA, Greider CW, Hannon GJ, Reddel RR, Graves JAM (2012) Extreme telomere length dimorphism in the Tasmanian devil and related marsupials suggests parental control of telomere length. PLoS One 7: e46195

    CAS  PubMed  PubMed Central  Google Scholar 

  • Blackburn EH (1991) Structure and function of telomeres. Nature 350: 569–573

    CAS  PubMed  Google Scholar 

  • Campisi J, Kim S, Lim C, Rubio M (2001) Cellular senescence, cancer and aging: the telomere connection. Experimental Gerontology 36: 1619–1637

    CAS  PubMed  Google Scholar 

  • Cattan V, Mercier N, Gardner JP, Regnault V, Labat C, Maki-Jouppila J, Nzietchueng R, Benetos A, Kimura M, Aviv A, Lacolley P (2008) Chronic oxidative stress induces a tissue-specific reduction in telomere length in CAST/Ei mice. Free Radical Biology and Medicine 8: 1592-8.

    Google Scholar 

  • Chan SRWL, and Blackburn EH, (2004) Telomeres and telomerase. Philosophical Transactions of the Royal Society B: Biological Sciences 359: 109–21

    CAS  Google Scholar 

  • Constantini D, Marasco V, Moller AP (2011) A meta-analysis of glucocorticoids as modulators of oxidative stress in vertebrates. Journal of Comparative Physiology B 181: 447–56

    Google Scholar 

  • Coppé JP, Kauser K, Campisi J, Beausejour CM (2006) Secretion of vascular endothelial growth factor by primary human fibroblasts at senescence. Journal of Biological Chemistry28: 29568–29574

    Google Scholar 

  • Ducray C, Pommier JP, Martins L, Boussin FD, Sabatier L (1999) Telomere dynamics, end-to-end fusions and telomerase activation during the human fibroblast immortalization process. Oncogene 18(29): 4211-4223

    CAS  PubMed  Google Scholar 

  • Ganem NJ and Pellman D (2007) Limiting the proliferation of polyploid cells. Cell131:437–440

    CAS  PubMed  Google Scholar 

  • Glaser R and Kiecolt-glaser JK (2005) Stress-induced immune dysfunction: implications for health.Nature Reviews Immunology 5: 243-251

    CAS  PubMed  Google Scholar 

  • Glei D, Goldman N, Risques RA, Rehkopf DH, Dow WH, Rosero-Bixby L, Weinstein M (2016) Predicting Survival from telomere length versus conventional

    PubMed  PubMed Central  Google Scholar 

  • Gomes NM (2011) Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination. Aging Cell 10: 761-8

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hackett JA and Greider CW (2002) Balancing instability: dual roles for telomerase and telomere dysfunction in tumorigenesis. Oncogene 21: 619–626

    CAS  PubMed  Google Scholar 

  • Hamede R, Lachish S, Belov K, Woods G, Kreiss A, Pearse AM, Lazenby B, Jones M, McCallum H (2012) Reduced effect of Tasmanian devil facial tumor disease at the disease front. Conservation Biology 26: 124–34

    PubMed  Google Scholar 

  • Hamede R, McCallum H, Jones, M (2013). Biting injuries and transmission of Tasmanian devil

    PubMed  Google Scholar 

  • Hamede R, Pearse AM, Swift K, Barmuta LA, Murchison EP, Jones ME (2015) Transmissible cancer in Tasmanian devils: localized lineage replacement and host population response. Proceedings of the Royal Society B: Biological Sciences282: 20151468

    PubMed  Google Scholar 

  • Haussmann MF, Winkler DW, Vleck CM (2005) Longer telomeres associated with higher survival in birds. Biology Letters 1: 212–4

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hawkins CE, Baars C, Hesterman H, Hocking GJ, Jones ME, Lazenby B, Mann D, Mooney N, Pemberton D, Pyecroft S, Restani M, Wiersma J (2006) Emerging disease and population decline of an island endemic, the Tasmanian devil Sarcophilus harrisii. Biological Conservation 131: 307–324

    Google Scholar 

  • Heidinger BJ, Blount JD, Boner W, Griffiths K, Metcalfe NB, Monaghan P (2012) Telomere length in early life predicts lifespan. Proceedings of the National Academy of Sciences, USA 109: 1743–8

    CAS  Google Scholar 

  • Joeng KS, Song EJ, Lee K, Lee J (2004) Long lifespan in worms with long telomeric DNA. Nature Genetics 36: 607–611

    CAS  PubMed  Google Scholar 

  • Jones ME, Cockburn A, Hamede R, Hawkins C, Hesterman H, Lachish S, Mann D, McCallum H, Pemberton D (2008) Life history change in disease-ravaged Tasmanian devil populations. Proceedings of the National Academy of Sciences, USA 105: 10023–10027

    CAS  Google Scholar 

  • Krtolica A, Parrinello S, Lockett S, Desprez PY, Campisi J (2001) Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proceedings of the National Academy of Sciences, USA98: 12072–7

    CAS  Google Scholar 

  • Kwon YM, Stammnitz MR, Wang J, Swift K, Knowles GW, Pye RJ, Kreiss A, Peck S, Fox S, Pemberton D, Jones ME, Hamede R, Murchison MP (2018) Tasman-PCR: a genetic diagnostic assay for Tasmanian devil facial tumour diseases. Royal Society Open Interface5: 180070.

    Google Scholar 

  • Ma, H, Zhou Z, Wei S, Liu Z, Pooley K, Dunning A, Svenson U, Roos G, Hosgood III D, Shen M, Wei Q (2011) Shortened telomere length is associated with increased risk of cancer: a meta-analysis. PLoS One 6: e20466

    CAS  PubMed  PubMed Central  Google Scholar 

  • Martin-Ruiz C, Baird D, Roger L, Boukamp P, Krunic D, Cawthon R, Dokter M, Harst PVD, Bekaert S, Meyer TD, Roos G, Svenson U, Codd V, Samani NJ, McGlynn L, Shiels PG, Pooley KA, Dunning AM, Cooper R, Wong A, Kingston A, Zglinicki TV (2015) Reproducibility of telomere length assessment: an international collaborative study. International Journal of Epidemiology 44: 1673-83

    PubMed  Google Scholar 

  • McCallum H, Jones ME, Hawkins C, Hamede R, Lachish S, Sinn D, Beeton N, Lazenby B (2009) Transmission dynamics of Tasmanian devil facial tumor disease may lead to disease-induced extinction. Ecology 90: 3379–3392

    PubMed  Google Scholar 

  • Miller W, Hayes VM, Ratan A, et al (2011) Genetic diversity and population structure of the endangered marsupial Sarcophilus harrisii (Tasmanian devil). Proceedings of the National Academy of Sciences, USA 108:12348–12353

    Google Scholar 

  • Mizutani Y, Tomita N, Niizuma Y, Yoda K (2013) Environmental perturbations influence telomere dynamics in long-lived birds in their natural habitat. Biology Letters9: 20130511

    PubMed  PubMed Central  Google Scholar 

  • Monaghan P and Haussmann MF (2006) Do telomere dynamics link lifestyle and lifespan? Trends in Ecology and Evolution 21: 47–53

    PubMed  Google Scholar 

  • Pearse AM, Swift K, Hodson P, Hua B, McCallum H, Pyecroft S, Taylor R, Eldridge MDB, Belov K (2012) Evolution in a transmissible cancer: A study of the chromosomal changes in devil facial tumor (DFT) as it spreads through the wild Tasmanian devil population. Cancer Genetics 205:101–102

    CAS  PubMed  Google Scholar 

  • Pye R, Hamede R, Siddle HV, Caldwell A, Knowles GW, Swift K, Kreiss A, Jones ME, Lyons AB, Woods GM (2016) Demonstration of immune responses against devil facial tumour disease in wild Tasmanian devils. Biology Letters 12: 20160553

    PubMed  PubMed Central  Google Scholar 

  • R Core Team (2015) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/

  • Richter T and von Zglinicki T (2007) A continuous correlation between oxidative stress and telomere shortening in fibroblasts. Experimental Gerontology 42: 1039–42

    CAS  PubMed  Google Scholar 

  • Romano GH, Harari Y, Yehuda T, Podhorzer A, Rubinstein L, Shamir R, Gottlieb A, Silberberg Y, Pe’er D, Ruppin E, Sharan R, Kupiec M (2013) Environmental stresses disrupt telomere length homeostasis. PLoS Genetics 9: e1003721

    CAS  PubMed  PubMed Central  Google Scholar 

  • Siddle HV, Kreiss A, Tovar C, Yuen CK, Cheng Y, Belov K, Swift K, Pearse AM, Hamede R, Jones ME, Skjodt K, Woods GM, Kaufman J (2013) Reversible epigenetic down-regulation of MHC molecules by devil facial tumour disease illustrates immune escape by a contagious cancer. Proceedings of the National Academy of Sciences, USA 110: 5103–8

    CAS  Google Scholar 

  • Symonds MRE and Moussalli A (2010) A brief guide to model selection, multimodel inference and model averaging in behavioural ecology using Akaike’s information criterion. Behavioral Ecology and Sociobiology65: 13–21

    Google Scholar 

  • Therneau T (2015) A Package for Survival Analysis in S. version 2.38 URL https://CRAN.R-project.org/package=survival

  • Ujvari B, Pearse AM, Taylor R, Pyecroft S, Flanagan C, Gombert S, Papenfuss AT, Madsen T, Belov K (2012) Telomere dynamics and homeostasis in a transmissible cancer. PLoS One7: e44085

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang N-P (2012) Telomeres and immune competency. Current Opinion in Immunology24: 470-475

    Google Scholar 

  • Webb CJ, Wu Y, Zakian VA (2013) DNA repair at telomeres: Keeping the ends intact. Cold Spring Harbor Perspectives in Biology5:a012666

    PubMed  PubMed Central  Google Scholar 

  • Weischer M, Nordestgaard, BG, Cawthon RM, Freiberg JJ, Tybjaerg-Hansen A, Bojesen SE (2013) Short telomere length, cancer survival, and cancer risk in 47102 individuals. Journal of the National Cancer Institute105: 459–68

    CAS  PubMed  Google Scholar 

  • Wentzensen IM, Mirabello L, Pfeiffer RM, Savage SA (2011) The association of telomere length and cancer: a meta-analysis. Cancer Epidemiology, Biomarkers, and Prevention20: 1238–50

    CAS  Google Scholar 

  • Zhang C, Chen X, Ying Zhou LL, Wang C, Hou S (2015) The Association between telomere length and cancer prognosis: evidence from a meta-analysis. PLoS One 10: e0133174

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was funded under NSF Grant DEB 1316549 and NIH Grant R01-GM126563 to AS and MJ as part of the joint NSF-NIH-USDA Ecology and Evolution of Infectious Diseases program. Animal use was approved under IACUC protocol ASAF#04392 at Washington State University. Fieldwork was funded by grants from the Australian Research Council to MJ (A00000162, LP0561120, LP0989613, DP110102656), several Eric Guiler Tasmanian devil grants, through the Save the Tasmanian devil Appeal of the University of Tasmania Foundation to R.H and M.J., and grants from the Ian Potter Foundation, the Australian Academy of Science (Margaret Middleton Fund), Estate of WV Scott, the National Geographic Society, the Mohammed bin Zayed Conservation Fund, and the Holsworth Wildlife Trust to MJ. MJ received support from an ARC Future Fellowship (FT100100250) and a Fulbright Tasmania Senior Scholarship, and RH from an ARC DECRA (DE170101116). We are grateful to M & C Walsh from Discovery Holiday Parks at Cradle Mountain, and the Tasmanian Parks and Wildlife Service at Freycinet, Cradle Mountain and Narawntapu for providing accommodation and logistic support during fieldwork and a large number of volunteers who helped to collect data. Forico Pty Ltd. provided land access and logistic support during fieldwork. We thank Jesse Brunner for assistance with hazard model analyses. We also thank Austin Patton, Alexandra Fraik, Lauren Ricci, Omar Cornejo and Paul Hohenlohe for rich discussions that improved the quality of this work.

Author information

Affiliations

  1. School of Biological Sciences, Washington State University, Pullman, WA, 99164-4236, USA

    Lane E. Smith, Austin H. Patton, Patrick A. Carter & Andrew Storfer

  2. School of Biological Sciences, University of Tasmania, Private Bag 55, Hobart, TAS, 7001, Australia

    Menna E. Jones & Rodrigo Hamede

  3. Department of Pathology, University of Washington School of Medicine, 1959 NE Pacific St., Seattle, WA, 98195, USA

    Rosana Risques

Authors
  1. Lane E. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Menna E. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rodrigo Hamede
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rosana Risques
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Austin H. Patton
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Patrick A. Carter
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Andrew Storfer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrew Storfer.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Smith, L.E., Jones, M.E., Hamede, R. et al. Telomere Length is a Susceptibility Marker for Tasmanian Devil Facial Tumor Disease. EcoHealth 17, 280–291 (2020). https://doi.org/10.1007/s10393-020-01491-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10393-020-01491-y

Keywords

  • Telomeres
  • Infectious disease
  • Devil facial tumor disease
  • DFTD
  • Wildlife health