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Sarcoptic mange severity is associated with reduced genomic variation and evidence of selection in Yellowstone National Park wolves (Canis lupus). DeCandia AL, Schrom EC, Brandell EE, Stahler DR, vonHoldt BM.Evolutionary Applications. 2020 Sep
Population genetic theory posits that molecular variation buffers against disease risk. Although this “monoculture effect” is well supported in agricultural settings, its applicability to wildlife populations remains in question. In the present study, we examined the genomics underlying individual‐level disease severity and population‐level consequences of sarcoptic mange infection in a wild population of canids. Using gray wolves (Canis lupus) reintroduced to Yellowstone National Park (YNP) as our focal system, we leveraged 25 years of observational data and biobanked blood and tissue to genotype 76,859 loci in over 400 wolves. At the individual level, we reported an inverse relationship between host genomic variation and infection severity. We additionally identified 410 loci significantly associated with mange severity, with annotations related to inflammation, immunity, and skin barrier integrity and disorders. We contextualized results within environmental, demographic, and behavioral variables, and confirmed that genetic variation was predictive of infection severity. At the population level, we reported decreased genome‐wide variation since the initial gray wolf reintroduction event and identified evidence of selection acting against alleles associated with mange infection severity. We concluded that genomic variation plays an important role in disease severity in YNP wolves. This role scales from individual to population levels, and includes patterns of genome‐wide variation in support of the monoculture effect and specific loci associated with the complex mange phenotype. Results yielded system‐specific insights, while also highlighting the relevance of genomic analyses to wildlife disease ecology, evolution, and conservation.
By Ivy Engel
Yellowstone’s gray wolf population was reintroduced in 1995. Those first 35 wolves were given vaccinations and treated for parasites to give them a better chance of survival. Since then, the packs have slowly come into contact with different diseases and parasites. In 2007, the first case of mange was reported in Yellowstone’s wolves and they’ve been dealing with it ever since.
Finding A Common Link
Mange is a fairly common mammalian disease caused by mites that results in itchy skin and can lead to hair loss from incessant scratching, as well as weight loss, secondary infections, and even death. But each animal deals with the disease in its own way, which led researchers to search for a commonality between wolves that beat the disease relatively easily.
“So we decided to look at the host genomics because we thought that could be a really fruitful part of the biology to look at because we do know that these wolves are being affected by the same mites. So it seems like the host immune response and differences therein might be causing these different phenotypes that we saw,” said Alexandra DeCandia, lead researcher on the study which was published in the journal Evolutionary Applications.
Yellowstone’s wolves made for a unique study population. Samples have been regularly gathered and stored since their reintroduction and the population has been heavily researched and monitored.
“We went freezer diving, which is as cold as it sounds!” laughed DeCandia.
Stored DNA samples allowed researchers to study wolves that are no longer alive.
Researchers were able to create detailed family trees including mange response using DNA from the decades old samples and recorded observations. This also meant that they had samples from over 400 wolves, even though the Yellowstone pack currently sits at around 100 individuals.
“So the real crux of this project is that it’s really interdisciplinary and really comprehensive and that we were able to combine genetic data, observational data, environmental data on these animals,” said DeCandia.
DeCandia and her team sequenced the genomes from each sample to pinpoint the genes associated with mange response. They were looking for different alleles, or variants of genes, that specify a certain response.
“And when we did this, we found that there were 410 variants that were significantly associated with severe mange. That was really exciting,” said DeCandia. “And when we looked into what those variants were, we found that a lot of them had a mutation of their genes, and had functions that were relating to immunity, relating to skin disorders – things like ichthyosis, where you have scaly skin, or alopecia, where you lose hair. These are things that we see in mange, things related to skin barrier integrity and related to autoimmunity and inflammation.”
Changing Genes Over Time
Yellowstone’s reintroduced pack has settled at around 100 individuals. The population serves as a source rather than a sink for surrounding areas, meaning that more wolves move out of the park than into it. Without new wolves bringing new genetics into the pack, there’s been some concern about inbreeding. Inbreeding lowers the genetic diversity of a population, which can cause health problems and increase susceptibility to disease.
“Wolves are really good at avoiding inbreeding, and so they’ve maintained really good levels of genetic diversity. But for a couple different reasons, we are still seeing some decreases in genetic diversity through time,” said DeCandia.
And, counterintuitively, this decrease in genetic diversity may be working in the wolves’ favor. Wolves with severe mange are less likely to breed.
“You tend to have worse mange symptoms, your body condition decreases. We also saw that, at the pack level, the breeding status of the pack was associated with mange,” said DeCandia. “Although here we think that it’s mainly decreasing the likelihood of breeding as opposed to the other way around because if you have poor body condition, you’re probably not going to be able to produce very healthy pups.”
While this decreases the gene pool, those alleles that DeCandia found that are linked to poor mange response are not passed on, making alleles linked to a better response more common in the pack. DeCandia and her team confirmed this by looking at how common they both were before and after mange entered Yellowstone.
“What we found is that since mange invaded the park in January 2007, those variants associated with severe mange are decreasing in the population, and in contrast, variants that are associated with mild mange are actually increasing in the population. And when you look before mange entered, when you look between 1995 and 2006, there’s no change in those variants in the population,” said DeCandia. “And so this is suggesting that mange is exerting a selective pressure on Yellowstone wolves, and is leading to genetic changes where we’re reducing the frequency of those harmful genetic variants through time.”
This combination makes it hard for researchers to predict how wolves in the future will handle diseases, especially mange.
“If wolves do continue to lose genetic diversity through time, eventually we might see individuals in the park exhibiting more severe symptoms. However, in addition to all of that going on, there is this other result where there is natural selection occurring where we do see a reduction of these harmful variants in the population. And so, if that happens through time, as we continue to see these reductions, then we would expect there to be milder mange as time goes on. And so what we’re left with are these two competing forces,” said DeCandia. “There’s some reductions in genetic diversity through time, but we’re also specifically reducing mange associated alleles through time, and so the speed of those processes is going to determine whether we see milder or more severe mange in the future.”