The genes of the major histocompatibility complex (MHC) are involved in acquired, specific immunity in vertebrates. Yet, 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 high-throughput 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 DNA-sequence variation or on physicochemical divergence of the translated peptides, covering a gradient of allelic to functional diversity. We found that i) body mass was not related to MHC-DRB diversity or genotype and that ii) adult survival probability was negatively associated with PAM distance, a corrected distance that considers the likelihood of each amino acid substitution to be accepted by the processes of natural selection. In addition, we found no evidence of fluctuating selection in time on MHC-DRB. 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). Further studies are needed to investigate this hypothesis. Our results suggest that genetic diversity is not always beneficial even in genes that are supposed to be strongly shaped by balancing selection.

We sampled individuals from the two herds of migratory caribou in Northern Québec and Labrador (Canada): Rivière-George herd (RG) and Rivière-aux-Feuilles herd (RAF) between 1996 and 2016. Tissue samples were collected (biopsies, hair or blood) and DNA was isolated. We used Illumina MiSeq technology to sequence a 250 bp fragment of the exon 2 of MHC-DRB gene (complete exon has 267 bp in caribou; Kennedy et al., 2010). We amplified this locus with the LA31 and LA32 primer pair designed by Sigurdardóttir et al. (1991). Complete methods of MHC genotyping and assessing MHC diversity are presented in the associated manuscript or on demande to the authors. Genome-wide diversity was also assessed using a ddRadSeq protocol. Complete methods of SNPs genotyping and genome-wide diversity computing are presented in Gagnon et al. (2019) or on demand to the authors.

References : 

Gagnon M, Yannic G, Perrier C, Côté SD (2019). No evidence of inbreeding depression in fast declining herds of migratory caribou. J Evol Biol 32: 1368–1381.

Kennedy LJ, Modrell A, Groves P, Wei Z, Single RM, Happ GM (2010). Genetic diversity of the major histocompatibility complex class II in Alaskan caribou herds. Int J Immunogenet 38: 109–119.

Sigurdardóttir S, Borsch C, Gustafsson K, Andersson L (1991). Cloning and sequence analysis of 14 DRB alleles of the bovine major histocompatibility complex by using the polymerase chain reaction. Anim Genet 22: 199–209.

Body mass and survival data could be provided on demand . Please read the "READ_ME.txt" file.