Chronic Wasting Disease is becoming increasingly prevalent in elk, deer, and reindeer populations in the Western and Midwestern United States. Some elk populations have shown increased frequency of alleles that allow for prolonged survival of the disease. 

What the media are calling “Zombie Deer Disease”1 is not, in fact, the zombie apocalypse feared by many around the world. In reality, the disease affecting numerous populations of deer, elk, and reindeer around the world is known as Chronic Wasting Disease (CWD). CWD is a form of Prion Disease, a class of fatal neurodegenerative diseases that affect many types of mammals, including humans, initially found in 1967.2 The foundation to understanding what is now known as Prion Disease came from many years of research on other forms of diseases like Kuru, which affected the Fore tribe in Papua, New Guinea,3 Scrapie, the sheep form, and Creutzfeld-Jakob disease, the human form. In the 1950’s, when much of this research was beginning, it was not known that these diseases were connected under the umbrella of Prion Disease. While some connections were made between the various diseases, the missing link that finally connected all of the puzzle pieces was Stanley Prusiner’s prion hypothesis, which named the prion protein (PrP) the infectious agent of the diseases.4 These proteins can misfold into harmful, pathogenic forms, ultimately leading to diseases such as Chronic Wasting Disease.

In CWD, the healthy prion protein, PrPC misfolds into the pathogenic PrPres, which is a form resistant to being broken down by the cell. CWD manifests itself in elk as loss of body weight, changes in behavior, and is always fatal.5 This form of Prion Disease is the only type to be seen in free-ranging populations which leads to the question of whether evolutionary adaptations related to disease are occurring. This type of selection for favorable alleles in a population over time due to a disease is known as pathogen-mediated selection.  Writing in the journal PNAS, Monello et al.6 examined whether this phenomenon occurs in wild elk populations in the Western United States.

In order to look into pathogen-mediated selection, the genotypes of the elk and which specific part influences CWD development must first be known. These questions have previously been answered. The gene sequence of the prion protein showed a polymorphism at codon 132 that results in a change in amino acids from Methionine (M) to Leucine (L).7 In populations of elk, the majority exhibit the MM genotype, indicating it is more common in both healthy and diseased populations than the L allele. It was also known that in populations exposed to CWD, elk with the MM genotype had a shorter incubation time for CWD while elk with the LL genotype had a longer incubation time.8 This means it took a longer amount of time for the disease to manifest in elk with the LL genotype than the MM genotype. This led researchers to believe the L allele may provide limited protection against CWD, as the elk survive longer but ultimately succumb to the fatality of CWD. Thus, researchers predicted that the frequency of the L allele may be growing, as the elk are able to reproduce before dying of CWD.

Monello et al. realized there had been no studies evaluating this selection for the L allele in free-ranging populations of elk. The researchers hypothesized that the frequency of the 132L allele increases in populations exposed to CWD for more than thirty years, and they found support for this prediction. Elk populations from Laramie Mountains (LARA), Rocky Mountain National Park (ROMO), Absaroka Range (ABSA), Theodore Roosevelt National Park (THRO), and Wind River Ranges (WIND) were studied. It was previously known that elk populations LARA and ROMO are affected by CWD, and this was confirmed by Monello et al. The other three elk populations studied have not been exposed to CWD.

The authors found LARA and ROMO populations expressed a L allele frequency two to three times larger than the frequency found in ABSA, THRO, and WIND populations. This higher allele frequency was found in concordance with a higher prevalence of CWD in the population. Monello et al. concluded that this evidence directly communicates pathogen-mediated selection in the elk populations exposed to CWD for thirty to fifty years or more. The frequency of the MM genotype was consistently greater than the ML or LL genotypes in all five populations, supporting the previous finding that the M allele is most commonly seen in wild elk populations. 

Monello et al. discuss the implications of pathogen-mediated selection in free ranging elk populations LARA and ROMO. While the authors are not certain whether this selection will continue, as there could be negative fitness costs associated with the L allele, they suggest that the L allele is not a permanent solution. Despite a longer survival rate, the elk with the L allele will still die from CWD. The authors also discuss the possibility of strains of the prion protein in CWD which could potentially overcome pathogen-mediated selection. Previous studies have identified strains of PrPSc in the sheep prion disease, Scrapie,9 which does not rule out strains of PrPres in elk. Moreover, elk with the L allele can give off PrPres before showing signs of CWD, which could lead to increased transmission of CWD to other elk in the population.10

The importance of this research comes from the potential for the spread of CWD to mammals other than the deer and elk populations. These infected animals are prevalent in many areas where hunting is more common. The fear associated with an increased prevalence of animals with CWD is that the disease could transmit to humans who eat infected meat, as with Mad Cow Disease in the 1990’s that came from eating beef infected with another type of prion disease called Bovine Spongiform Encephalopathy (BSE). Recent studies have found that the misfolded, pathogenic prion protein in CWD can potentially shift the healthy human PrPC to its misfolded and pathogenic form, PrPSc.11 Thus, if there is a chance elk are evolving to favor prolonged survival of CWD in their populations, it would be important to know and confirm with more research whether this form of prion disease can be transmitted to humans.

With this finding, the authors propose researchers can examine the type of selection occurring in wild populations, and whether it continues to select for the L allele, or a balancing effect takes place and either maintains or reduces the frequency of the L allele. On a different note, CWD has been found in places other then the Western United States. It has been observed in other parts of the USA, Canada, South Korea, and most recently in Europe. In order to better understand this disease and the problems that may arise from it for both animals and humans, continued studies in different geographical locations may be warranted. Even though the zombie deer apocalypse is not wreaking havoc upon humanity at the moment, precautions must be taken to ensure the disease is kept under control in wild populations and not spread to other species.

Figure 1. Methodology of pathogen-mediated selection in general populations. Elk with the different alleles shown above have relatively different life spans with chronic wasting disease, with L allele elk surviving the longest.

References

1. MacMillan, A. (2019). ‘Zombie Deer Disease’ Is Infecting Animals Across the Country—Are Humans at Risk? Health. Retrieved from www.health.com/condition/infectious-diseases/zombie-deer-chronic-wasting
2. Edmunds, D. R., Kauffman, M. J., Schumaker, B. A., Lindzey, F. G., Cook, W. E., Kreeger, T. J., … & Cornish, T. E. (2016). Chronic wasting disease drives population decline of white-tailed deer. PLoS One, 11, e0161127.
3. Zabel, M. D., & Reid, C. (2015). A brief history of prions. Pathogens and disease, 73(9). doi:10.1093/femspd/ftv087
4. Prusiner S. B. (1998). Prions. Proceedings of the National Academy of Sciences of the United States of America, 95(23), 13363–13383.
5. Williams, E.S., Miller, M.W. (2002). Chronic wasting disease in deer and elk in North America. Rev Sci Tech 21:305-316.
6. Monello, R.J., Galloway, N.L., Powers, J.G., Madsen-Bouterse, S.A., Edwards, W.H., Wood, M.E.,… Wild, M.A. (2017). Pathogen-mediated selection in free-ranging elk populations infected by chronic wasting disease. PNAS, 114(46), 12208-12212. doi.org/10.1073/pnas.1707807114
7. O’Rourke, K. I., Besser, T. E., Miller, M. W., Cline, T. F., Spraker, T. R., Jenny, A. L., … & Williams, E. S. (1999). PrP genotypes of captive and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease. Journal of General Virology, 80:2765-2679.
8. Williams, A. L., Kreeger, T. J., & Schumaker, B. A. (2014). Chronic wasting disease model of genetic selection favoring prolonged survival in Rocky Mountain elk (Cervus elaphus). Ecosphere, 5(5), 1-10.
9. Bruce M, Boyle A, Cousens S, McConnell I, Foster J, Goldmann W, Fraser H. J. (2002). Strain characterization of natural sheep scrapie and comparison with BSE. Gen. Virol. 83(3):695-704 doi:10.1099/
10. Cheng, Y. C., Hannaoui, S., John, T. R., Dudas, S., Czub, S., & Gilch, S. (2016). Early and non-invasive detection of chronic wasting disease prions in elk feces by real-time quaking induced conversion. PloS one, 11(11), e0166187.
11. Barria, M. A., Libori, A., Mitchell, G., & Head, M. W. (2018). Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions. Emerging Infectious Diseases, 24(8), 1482-1489. dx.doi.org/10.3201/eid2408.161888.