Sarcoptic mange severity is associated with reduced genomic variation and evidence of selection in Yellowstone National Park wolves (Canis lupus)

Abstract

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.

Keywords: RAD‐sequencing; ectoparasite; genetics; infection severity; mite infestations; natural selection; sarcoptic mange; wildlife disease.

FIGURE 1

Annual wolf counts recorded in December 1995 through 2019 with years of CDV outbreaks, mange invasion, and maximum mange burden indicated (figure adapted from Almberg et al., 2012). Large circles represent large‐scale CDV outbreaks, with smaller circles indicative of smaller outbreaks

FIGURE 2

Genetic diversity statistics for mange‐infected wolves grouped by mild (highest mange score 1), moderate (highest mange score 2), and severe (highest mange score 3) infection severity. Metrics include the following: (a) percentage polymorphic loci, (b) number of private alleles, (c) observed heterozygosity, (d) expected heterozygosity, (e) minor allele frequency, (f) nucleotide diversity, (g) rarefied mean allelic richness, and (h) rarefied mean private allelic richness

FIGURE 3

Rarefied private allelic richness shared between mange severity classes

FIGURE 4

Fixed effects included environmental, pack‐level, and individual‐level variables. Asterisks indicate variables included in the final model. Figure created with BioRender

FIGURE 5

Mean allelic richness rarefied to 20 individuals for all wolves (black solid line) and all known breeders (brown dashed line) alive in each year

FIGURE 6

Posterior predictions of the average changes in frequency through time for alleles not associated, positively associated, and negatively associated with mange severity, with 95% credible intervals surrounding the mean. Nonassociated alleles comprise a randomly selected subset of 500 loci. The same analysis was repeated to assess changes in allele frequency (a) after mange invasion of YNP and (b) before mange invasion of YNP

FIGURE 7

Sarcoptic mange was implicated in the dissolution of the Druid Peak pack in late 2009 and early 2010, when numerous pack members became infected. This pedigree contains a subset of Druid wolves shaded to indicate mange infection severity. Genotype at the mange‐associated locus contained in gene PTPN6 is indicated, when available, to illustrate how family‐based association links genotypes with phenotypes while controlling for relatedness. Similar analyses were conducted for all loci analyzed by GEMMA. Dashed lines connect the same individual to parentage events occurring in different parts of the pedigree