Divergent allele advantage at MHC-DRB through direct and maternal genotypic effects and its consequences for allele pool composition and mating

Abstract

It is still debated whether main individual fitness differences in natural populations can be attributed to genome-wide effects or to particular loci of outstanding functional importance such as the major histocompatibility complex (MHC). In a long-term monitoring project on Galápagos sea lions (Zalophus wollebaeki), we collected comprehensive fitness and mating data for a total of 506 individuals. Controlling for genome-wide inbreeding, we find strong associations between the MHC locus and nearly all fitness traits. The effect was mainly attributable to MHC sequence divergence and could be decomposed into contributions of own and maternal genotypes. In consequence, the population seems to have evolved a pool of highly divergent alleles conveying near-optimal MHC divergence even by random mating. Our results demonstrate that a single locus can significantly contribute to fitness in the wild and provide conclusive evidence for the 'divergent allele advantage' hypothesis, a special form of balancing selection with interesting evolutionary implications.

Keywords: Galápagos sea lion; major histocompatibility complex; overdominance; reproductive success; sequence divergence; survival.

Figure 1.

Survival in juvenile Galápagos sea lions with respect to individual and maternal MHC genotype. MHC divergence is expressed as the number of different amino acids [aa] between an individual's two MHC-DRB alleles. The black line shows the effect of the individual genotype and the grey line corresponds to the effect of the maternal genotype. Dashed lines indicate 95% CIs.

Figure 2.

Reproductive success of female and male Galápagos sea lions with respect to their MHC divergence. MHC divergence is expressed as the number of different amino acids [aa] between an individual's two MHC-DRB alleles. (a) Female reproductive success is given as the cumulative number of offspring produced over at least 8 years that survive their first year. For better visualization, boxplots of MHC divergence are shown for each class of reproductive success. (b) Male reproductive success is defined as achieving paternity or not during a reproductive season. In each panel, predictions of the best model are presented as a black line, which corresponds well with the visual pattern inferred by non-parametric smoothing (grey line).

Figure 3.

Correlation between average pairwise allele divergence and allele frequency. For all 27 detected MHC-DRB alleles, their frequency in the population (log-transformed) is plotted against their average pairwise amino acid divergence to the ten most common MHC-DRB alleles (defined by a minimum allele frequency of 5%, see also electronic supplementary material, figure S3).