Age-dependent selection on MHC class 2 variation in a free-living ruminant

Abstract

The major histocompatibility complex (MHC) is the most variable gene family known in vertebrates. Parasite-mediated selection (PMS) is believed to be the main force maintaining diversity at MHC genes, but it has proven hard to demonstrate the exact PMS regime that is acting in natural populations. Demonstrating contemporary selection on MHC alleles is not trivial, and previous work has been constrained by limited genetic tools, low sample sizes, short time scales and anticonservative statistical approaches. Here, we use a conservative statistical approach to examine associations between MHC genes and fitness components, using haplotypes of expressed MHC class II genes in a large sample of Soay sheep (Ovis aries) monitored over their lifetimes between 1989 and 2012. Of the eight MHC haplotypes (A-H) identified, we found that haplotype C was associated with decreased male breeding success, haplotype D was associated with increased female life span, and haplotype F was associated with decreased female life span. Consistent with the increased lifespan in females, haplotype D has increased in frequency throughout the study period. Our results suggest the existence of contemporary balancing selection on MHC class II genes in Soay sheep as might be expected under the hypotheses of rare allele advantage or fluctuating selection and do not support an effect of heterozygous advantage.

Associations between MHC class II variation and phenotypic traits in a free-living sheep population

“…First, we only found association between MHC heterozygosity or divergence and IgA level in lambs. This result is consistent with a previous study of MHC-fitness associations which identified a positive association between MHC divergence and juvenile survival (Huang, Dicks et al 2020) and indicates that there may be an age-dependent MHC heterozygote advantage or MHC divergent allele advantage in Soay sheep acting via IgA. However, the model including MHC heterozygosity, individual MHC haplotypes and MHC divergence showed neither MHC heterozygosity nor MHC divergence was significant (Supplementary 8).…”

“…In term of specific MHC haplotype, haplotype C was positively associated with both older IgE level but negatively associated with adult male breeding success (including both yearling and adult sheep). However, haplotype F was associated with decreased adult female life span but not associated with antibodies (Huang, Dicks et al 2020). Although lamb IgA level was not significantly associated with juvenile survival, there is a coherent pattern between lamb IgA level and FEC (Sparks, Watt et al 2018).…”

Associations between MHC class II variation and phenotypic traits in a free-living sheep population

“…We also found that a haplotype (C) is associated with decreased adult male breeding success while another haplotype (F) is associated with decreased adult female life span. In addition, the frequency of haplotype D has increased significantly through the study period more than expected by drift (Huang, Dicks et al 2020). These results indicate that there is contemporary selection on MHC class II variation in Soay sheep.…”

“…A previous study of Soay sheep alive between 1985 and 1994 found negative associations between two alleles at an MHC-linked microsatellite and a key parasite measurement, strongyle faecal egg count (FEC), and these two alleles were also positively associated with juvenile survival (Paterson, Wilson et al 1998). Recently, we reported associations between Soay sheep MHC class II variation and fitness measurements (Huang, Dicks et al 2020). These new findings were enabled by major advances in the characterisation of MHC variation in Soay sheep.…”

“…After quality control, which included pedigree checking, the diplotypes of 5349 individuals sampled between 1985 and 2012 were identified. For each individual successfully diplotyped, the functional divergence between an individual's two haplotypes (MHC divergence) was measured as the proportion of the amino acid sequence that differed between the two MHC haplotypes (p-distance) (Henikoff 1996, Huang, Dicks et al 2020.…”