Adult survival in migratory caribou is negatively associated with MHC functional diversity

Abstract

Genes of the major histocompatibility complex (MHC) are involved in acquired immunity in vertebrates. Only a few studies have investigated the fitness consequences of MHC gene diversity in wild populations. Here, we looked at the association between annual survival and body mass and MHC-DRB exon 2 (MHC-DRB) genetic diversity, obtained from highthroughput sequencing, in two declining migratory caribou (Rangifer tarandus) herds. To disentangle the potential direct and general effects of MHC-DRB genetic diversity, we compared different indices of diversity that were either based on DNAsequence variation or on physicochemical divergence of the translated peptides, thereby covering a gradient of allelic-tofunctional diversity. We found that (1) body mass was not related to MHC-DRB diversity or genotype, and (2) adult survival probability was negatively associated with point accepted mutation distance, a corrected distance that considers the likelihood of each amino acid substitution to be accepted by natural selection. In addition, we found no evidence of fluctuating selection over time on MHC-DRB diversity. We concluded that direct effects were involved in the negative relationship between MHC functional diversity and survival, although the mechanism underlying this result remains unclear. A possible explanation could be that individuals with higher MHC diversity suffer higher costs of immunity (immunopathology). Our results suggest that genetic diversity is not always beneficial even in genes that are likely to be strongly shaped by balancing selection.

Selection and demography drive range-wide patterns of MHC-DRB variation in mule deer

“…Heterozygote deficiencies at the MHC locus were found in 50% of the mule deer populations surveyed, whereas microsatellites were consistently in Hardy–Weinberg equilibrium (6 loci exhibited no deviations, and the other 3 loci exhibited heterozygote deficiencies in 1 or 2 populations). Other cervids also exhibit heterozygote deficiencies at the MHC DRB locus, including in white-tailed deer, caribou, and moose [ 58 , 66 , 69 , 76 ]. An observed heterozygosity excess would be expected if there were a fitness advantage for MHC heterozygotes, through either pathogen-mediated natural selection or sexual selection (MHC-disassortative mating).…”

“…Selection against heterozygotes is rare, but not unheard of. For example, in caribou, high heterozygosity is associated with decreased immunocompetence, offering a potential mechanism limiting excess heterozygosity in ungulates [ 76 ]. Further exploration of immunological costs associated with heterozygosity would help determine whether mule deer experience similar pressures.…”

“…Spatially heterogenous selection would be expected to maintain polymorphism and facilitate local adaptation [ 30 , 51 , 53 , 85 , 96 – 98 ]. High polymorphism across populations at MHC genes may help populations respond to a wide variety of pathogens and increase population fitness, though costs to maintain diversity may impose an upper limit [ 76 ]. In mule deer, low rates of gene duplication and allelic richness compared to other mammals suggest that such a trade-off may not be critical in ungulates [ 18 ].…”

Functional immune diversity in reindeer reveals a high Arctic population at risk

“…Such geographical changes in pathogen distribution could pose a future challenge to Norwegian reindeer. Previous studies on MHC diversity in reindeer investigated MHCII diversity using genomic DNA (Mikko et al, 1999;Kennedy et al, 2011;Taylor et al, 2012;Gagnon et al, 2020) and there have been no investigations of expressed MHCI or MHCII diversity. With the availability of reindeer genome sequences, we aim to define classical versus non-classical MHC genes and use these data to assess expressed MHC diversity in samples from semi-domesticated reindeer from Northern Norway, wild reindeer from Southern Norway and reindeer from the high Arctic Svalbard archipelago.…”

Adverse effects of Diptera flies on northern ungulates: Rangifer, Alces, and Bison

“…The major histocompatibility complex (MHC) is a large library of genes that code for antigens. High diversity of the MHC is associated with reduced survivorship in adult Rangifer tarandus (Gagnon et al 2020), which suggests that sustaining physiological resistance to pathogens and parasites is costly. Sociality also affects transmission of pathogens; low genetic diversity of MHC in Alces alces is consistent with a solitary lifestyle and a low risk of transmission within the species (Swialocka et al 2020).…”