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Père David’s deer gene variants may ward off CWD

Père David’s deer gene variants may ward off CWD

By Buckmasters Online

It seems unlikely that an endangered Asian deer named for French priest and naturalist Armand David who first observed its existence, is the same deer species saved from extinction by a British duke, and the same deer species researchers have found has two gene variants with the potential to unlock part of the Chronic Wasting Disease mystery.

The story of Père David's deer jumps all over the world, from 19th century China and Europe to an English estate, to 21st century researchers in Illinois, and a multitude of zoos, parks and game reserves where the deer, now in the thousands, live. What a journey this deer species has taken.

Père David's deer is truly like no other. The only member of its genus, its only known population during the 19th century was found in the Emperor of China’s game park near Beijing. French naturalist Henri Milne-Edwards classified the deer.

Tragically, most of the Chinese herd died in a great flood in 1895, and many of the remaining deer were killed during the Boxer Rebellion in 1900. Of the few remaining deer transported to European zoos for breeding and exhibition, it was Herbrand Russell, the 11th Duke of Bedford, who saved the species. He searched for and acquired the last 11 captive deer and bred them on his Woburn Abbey estate.

A century later, the original group of Père David's deer are estimated now to number about 5,000 animals. The World Wildlife Fund reports a group of 38 deer reintroduced in the National Nature Reserve in central China have now expanded to 600.

Initially, the hope was simply that the number of deer in the small gene pool would survive, but scientists have noted the deer’s natural survival instincts appear reawakened when they returned to their ancestors’ place of origin in the Yangtze basin. In 2016, China’s Forestry Administration released 16 deer in an unfenced park near the Yangtze River, returning Père David’s deer to the wild for the first time since their near extinction a century ago.

Père David's deer are unique members of the Cervidae family. Fully grown, these sturdy, athletic animals can tip the scales between 400 and 550 pounds. They have long faces, small ears, large antlers, long and brushy tails and cow-shaped hooves they use as tools, with webbing between their toes for swimming.

But then a question raised about the future for the deer was troubling.

Despite a success story that spans centuries, Père David's deer would be vulnerable, should they become infected by Chronic Wasting Disease, the widespread, always fatal disease affecting North America’s cervids, now spreading across the world.

Wonderful discoveryThere are reasons to be optimistic, according to a University of Illinois study where researchers identified Père David’s deer as possessing gene variants that may naturally protect them from the threats of Chronic Wasting Disease.

“The gene variants we found in Père David’s deer have been linked to reduced susceptibility to CWD in other species. Studies would have to be done in this species to know if the gene variants really have the protective effect, but this is a good starting point to understand potential susceptibility,” according to Tolulope Perrin-Stowe, now a postdoctoral researcher at the University of Wisconsin-Madison. Perrin-Stowe led the research during her doctoral program at the University of Illinois.

“Infectious prions are such an odd biological entity, because every other infectious agent – viruses, bacteria – contains nucleic acids. Infectious prions are just proteins that are able to latch on to normal proteins and induce a conformation change that makes them infectious as well,” Perrin-Stowe says.

CWD is caused by infectious prions that trigger normal proteins in the brain to fold abnormally and clump together.

All mammals make normal prion proteins, believed to play a role in the brain’s biochemistry, and scientists know which gene codes for them. Things only go wrong when the gene mutates, as in certain forms of Creutzfeldt-Jakob disease, or when an infectious prion, the misfolded form of the normal protein, enters the host. That initiates a chain reaction causing normal prion proteins to change shape and go rogue.

The gene for prion protein synthesis, PRNP, is highly conserved (meaning it is nearly universal and unchanged after millions of years) across mammalian species. There is little variation in the gene among individuals, even across species or through evolutionary time. Highly conserved genes are usually important for basic biological functioning, but scientists still don’t have a clear understanding of the role prion proteins play in our brains.

It’s also important to consider the genetic implications of Père David’s deer’s near-extinction.

“When populations grow from very few founder individuals – in this case, the 11 deer that re-started the species – genetic diversity is typically much lower than in populations that avoid such bottleneck events,” says Alfred Roca, professor in the Department of Animal Sciences at U of I and study co-author.

Given this unique genetic scenario, it was a double surprise when the researchers found not one but two PRNP gene variants in Père David’s deer.

“We would assume because the current population is descended from only 11 founders that there wouldn't be much variation in the gene. It was surprising to find two variant forms, one of which is strongly associated with reduced CWD susceptibility in other deer species,” Perrin-Stowe says.

Wonderful discoveryPerrin-Stowe and her colleagues sequenced the coding region of the PRNP gene in 27 Père David’s deer from zoos in Ohio, California and New York. Most of the 27 carried the gene variant previously found to be associated with lower CWD susceptibility in other deer species, but a few individuals had a variant never before described in deer. According to research in sheep, that variant may also provide a protective benefit against CWD.

Although the results are promising, researchers say the deer would have to be exposed to CWD to see if they’re really resistant. Natural exposure hasn’t happened so far, fortunately, and experimental exposure would be unrealistic in an endangered species.

For now, the genetic variants remain a good sign, not a guarantee.

“The genetic variations in the prion gene in this endangered species are analogous to some of the genetic variations we have found in the Illinois white-tailed deer. Studies under captive field conditions using natural mechanisms of exposure to CWD could provide further information about the ability of these variants to reduce the risk of infection to CWD, according to Nohra Mateus Pinilla, director of the veterinary epidemiology laboratory of the Illinois Natural History Survey and study co-author.

“Nevertheless, the findings in this study give us hope the Père David’s deer populations have something that may help them fight CWD if they become exposed.”

Resources: University of Illinois Department of Animal Science, College of Agriculture, Consumer and Environmental Sciences; World Wildlife Fund; the article, “Variation in the PRNP gene of Père David’s deer (Elaphurus davidianus) may impact genetic vulnerability to chronic wasting disease,” published in Conservation Genetics [DOI: 10.1007/s10592-021-01419-1]. Study authors: Tolulope Perrin-Stowe, Yasuko Ishida, Emily Terrill, Dan Beetem, Oliver Ryder, Jan Novakofski, Nohra Mateus-Pinilla, and Alfred Roca. This work was supported by the Cooperative State Research, Education, and Extension Service, U.S. Department of Agriculture, under project number ILLU 875-952 and ILLU 538-966, and by the Francis M. and Harlie M. Clark Research Support Grant.

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