Patterns of MHC-DRB1 polymorphism in a post-glacial island canid, the Newfoundland red fox (Vulpes vulpes deletrix), suggest balancing selection at species and population timescales

Abstract

As the only native insular Newfoundland canid between the extinction of the wolf in the 1930s and the recent arrival of coyotes, the red fox (Vulpes vulpes deletrix Bangs 1898) poses interesting questions about genetic distinctiveness and the post-glacial colonization history of the island's depauperate mammalian fauna. Here, we characterized genetic variability at the major histocompatibility complex (MHC) class II DR β1 domain (DRB1) locus in 28 red foxes from six sampling localities island-wide and compared it with mitochondrial control region (CR) diversity and DRB1 diversity in other canids. Our goals were to describe novel DRB1 alleles in a new canid population and to make inferences about the role of selection in maintaining their diversity. As in numerous studies of vertebrates, we found an order-of-magnitude higher nucleotide diversity at the DRB1 locus compared with the CR and significantly positive nonsynonymous-to-synonymous substitution ratios, indicative of selection in the distant past. Although the evidence is weaker, the Ewens-Watterson test of neutrality and the geographical distribution of variation compared with the CR suggest a role for selection over the evolutionary timescale of populations. We report the first genetic data from the DRB1 locus in the red fox and establish baseline information regarding immunogenetic variation in this island canid population which should inform continued investigations of population demography, adaptive genetic diversity, and wildlife disease in red foxes and related species.

Keywords: Balancing selection; DRB1; Host immunogenetics; Major histocompatibility complex; Red fox; Tests of neutrality.

Fig. 1

Geographic location of the six sampled island Newfoundland red fox populations (Northeast Coast, Central Newfoundland, Avalon Peninsula, West Coast, South Coast, Northern Peninsula)

Fig. 2

Variable sites in eight DRB1 alleles identified among 28 red foxes from six Newfoundland island localities. Alleles are designated Vuvu DRB1-8, in order of frequency of occurrence. a Thirty-seven variable nucleotide sites, grouped according to codon membership. Second position sites are shown in bold; third position sites are italicized. b Twenty variable amino acid sites, aligned with respect to the appropriate nucleotide codon

Fig. 3

Neighbor-joining phylogenies among red fox DRB1 alleles and DRB1 alleles from other canids accessed from GenBank. Accession numbers are given with taxon name, and allele designations are as stated in the accession. Numbers above nodes are percentage support from 10,000 bootstrap replicates. The blocks to the right show the amino acid associated with each taxon at selected sites identified by HyPhy, as discussed in the text. These correspond to sites 64 (a) and 30, 56, and 67 (b) in Fig. 2b. a Vulpes only phylogeny: Vula = Vulpes lagopus and Vuvu DRB1-Vuvu DRB8 designate the Vulpes vulpes alleles. b Vulpes, Urocyon, and Canis lupus comprehensive phylogeny. Urli = Urocyon littoralis and Calu = Canis lupus. Due to the very large number of alleles available from Canis sp., Canis lupus was selected here to represent the lineage