Contrasting epidemic histories reveal pathogen-mediated balancing selection on class II MHC diversity in a wild songbird

Abstract

The extent to which pathogens maintain the extraordinary polymorphism at vertebrate Major Histocompatibility Complex (MHC) genes via balancing selection has intrigued evolutionary biologists for over half a century, but direct tests remain challenging. Here we examine whether a well-characterized epidemic of Mycoplasmal conjunctivitis resulted in balancing selection on class II MHC in a wild songbird host, the house finch (Carpodacus mexicanus). First, we confirmed the potential for pathogen-mediated balancing selection by experimentally demonstrating that house finches with intermediate to high multi-locus MHC diversity are more resistant to challenge with Mycoplasma gallisepticum. Second, we documented sequence and diversity-based signatures of pathogen-mediated balancing selection at class II MHC in exposed host populations that were absent in unexposed, control populations across an equivalent time period. Multi-locus MHC diversity significantly increased in exposed host populations following the epidemic despite initial compromised diversity levels from a recent introduction bottleneck in the exposed host range. We did not observe equivalent changes in allelic diversity or heterozygosity across eight neutral microsatellite loci, suggesting that the observations reflect selection rather than neutral demographic processes. Our results indicate that a virulent pathogen can exert sufficient balancing selection on class II MHC to rescue compromised levels of genetic variation for host resistance in a recently bottlenecked population. These results provide evidence for Haldane's long-standing hypothesis that pathogens directly contribute to the maintenance of the tremendous levels of genetic variation detected in natural populations of vertebrates.

Figure 1. Multi-locus class II major histocompatibility complex (MHC) diversity and house finch disease resistance.

MHC class II diversity as measured by single strand nuclear polymorphism predicts the severity of house finch (Carpodacus mexicanus) conjunctivitis in response to experimental infection with Mycoplasma gallisepticum (MG). All bars indicate one standard error around the mean.

Figure 2. Epidemic associated changes in functional and neutral genetic diversity in house finches (Carpodacus mexicanus).

Red indicates “pre” and yellow “post” values for control, western (left) and exposed, eastern (right) house finch populations across equivalent time periods. A) Tajima's D calculated from a portion of exon 2 of the class II Major Histocompability Complex (MHC) B) individual-level diversity amplified from multi-locus MHC class II, and C) microsatellite allelic diversity. Inset map shows the native (left) and introduced (right) range of the house finch. All bars indicate one standard error (s.e.m.) around the mean (*p<0.05; **p<0.01).