ALBERT

Description: In vertebrates, genes of the major histocompatibility complex (MHC), with their pronounced polymorphism, potentially represent outstanding examples for the selective advantages of genetic diversity (1). Theoretical models predicted that, within an individual, MHC alleles can be subjected to two opposing selective forces, resulting in an optimal number of genes at intermediate individual MHC diversity (2, 3). Diversifying selection increases heterozygosity and enables wider recognition of pathogens (4). This process is opposed by the need to delete T cells that react with self peptide–MHC combinations (5) from the repertoire, which has been proposed as a possible mechanism constraining expansion of MHC genes. Because too high MHC diversity might delimit T cell diversity, it might also impose limitations on the efficiency of pathogen recognition. However, empirical evidence demonstrating fitness benefits in terms of parasite resistance caused by this type of optimal MHC diversity has been lacking. Therefore, we tested whether three-spined sticklebacks (Gasterosteus aculeatus L.) carrying an intermediate level of individual MHC diversity also displayed the strongest level of resistance against parasite infection. Sticklebacks are particularly suited to test MHC optimality, because MHC class II genotypes can differ markedly in the number of MHC class IIB alleles (6). We caught fish from an outbred population and used these to breed six sibships of immunologically naïve fish (i.e., they had no previous contact to parasites). Immunogenetic diversity ranged from three to nine MHC class IIB alleles found in reverse-transcribed messenger RNA (mRNA) [see (6) for details on genotyping]. The MHC genotypes within these sibships segregated above and below the hypothesized optimal number of ∼5 MHC class IIB alleles, which had previously been estimated in an epidemiological field survey (7). In individual infection treatments, fish from all sibships were simultaneously exposed to three of the most abundant parasite species identified in the field (Fig. 1A) (8). After two rounds of infection, separated by an interval of 8 weeks, we found a significant minimal mean infection rate at an intermediate number of individual MHC class IIB variants [i.e., 5.82 expressed alleles (Fig. 1B)]. This result was also confirmed when sibships were considered separately [i.e., 4.96 alleles (Fig. 1C)] (9). The strong pattern only appeared when infection with all three parasites was accounted for simultaneously. This may not be surprising, because single alleles are expected to correlate with single diseases and multiple alleles can contribute to resistance against several infectious agents (2).

Description: Genetic variability of marine fish species is much higher than in most other vertebrates. Nevertheless, some species with large population sizes including flatfish such as European plaice Pleuronectes platessa show signs of population collapse and inbreeding. Taking plaice as a flagship example for fisheries-induced genetic changes also affecting the Wadden Sea, we determined the amount of genetic variability at antigen-presenting genes of the Major Histocompatibility Complex (MHC) and its potential interaction with the microbiota associated to gill tissue using a next-generation parallel tag sequencing approach. Genetic variation at MHC class IIB genes was extremely large, with 97 alleles found in 40 fish from different age cohorts. Although a strong signal of positive selection was present (dN/dS = 4.01) and we found significantly higher allelic diversity in 0+ fish than in older age classes, the amount of genetic variation maintained within the population may not have exceeded neutral expectations derived from mitochondrial markers. Associated microbes revealed significant spatiotemporal structure with 0+ fish displaying the highest microbial diversity as well as the highest diversity of potentially pathogenic genera. Overall the correlation between MHC genotypes and bacterial abundance was weak, and only few alleles significantly correlated with certain bacterial genera. These associations all conferred susceptibility (i.e. presence of an allele correlated to higher number of bacteria), either suggesting age-dependent selection on common alleles or weak selection on resistance against these bacterial genera. Taken together, our data suggest that selection coefficients of balancing selection maintaining immunogenetic diversity may be relatively small in large marine populations. However, if population sizes are further reduced by overharvesting, the response to increasing balancing selection coefficients will be largely unpredictable and may also negatively influence the adaptive potential of populations.