Data from: Parasite-mediated selection drives an immunogenetic tradeoff in plains zebras (Equus quagga)

Pathogen evasion of the host immune system is a key force driving extreme polymorphism in genes of the major histocompatibility complex (MHC). Although this gene family is well characterized in structure and function, there is still much debate surrounding the mechanisms by which MHC diversity is selectively maintained. Many studies have investigated relationships between MHC variation and specific pathogens, and have found mixed support for and against the hypotheses of heterozygote advantage, frequency-dependent or fluctuating selection. Few, however, have focused on the selective effects of multiple parasite types on host immunogenetic patterns. Here, we examined relationships between variation in the equine MHC gene, ELA-DRA, and both gastrointestinal (GI) and ectoparasitism in plains zebras (Equus quagga). Specific alleles present at opposing population frequencies had antagonistic effects, with rare alleles associated with increased GI parasitism and common alleles with increased tick burdens. These results support a frequency-dependent mechanism, but are also consistent with fluctuating selection. Maladaptive GI parasite 'susceptibility alleles' were reduced in frequency, suggesting that these parasites may play a greater selective role at this locus. Heterozygote advantage, in terms of allele mutational divergence, also predicted decreased GI parasite burden in genotypes with a common allele. We conclude that an immunogenetic trade-off affects resistance/susceptibility to parasites in this system. Because GI and ectoparasites do not directly interact within hosts, our results uniquely show that antagonistic parasite interactions can be indirectly modulated through the host immune system. This study highlights the importance of investigating the role of multiple parasites in shaping patterns of host immunogenetic variation.病原体逃逸宿主免疫系统是驱动主要组织相容性复合体（MHC）基因极端多态性的关键选择压力。尽管该基因家族的结构与功能已得到充分解析，但围绕MHC多样性如何通过选择得以维持的分子机制，学界仍存在诸多争议。诸多研究已探讨MHC变异与特定病原体间的关联，并对杂合子优势（heterozygote advantage）、频率依赖选择（frequency-dependent selection）及波动选择（fluctuating selection）等假说给出了混杂的验证结果，既有支持也有质疑。然而，鲜有研究聚焦于多种寄生虫类型对宿主免疫遗传模式的选择效应。本研究以平原斑马（Equus quagga）为研究对象，探究其马MHC基因ELA-DRA的变异与胃肠道（GI）寄生及体外寄生的关联。研究发现，在种群中频率分布对立的特定等位基因呈现拮抗效应：稀有等位基因与更高的胃肠道寄生虫负荷相关，而常见等位基因则伴随更高的蜱虫寄生量。上述结果支持频率依赖选择机制，但也与波动选择假说相符。不利于宿主的胃肠道寄生虫‘易感等位基因’频率偏低，提示这类寄生虫在该基因座上可能发挥了更强的选择作用。就等位基因突变分化程度而言，携带常见等位基因的杂合子基因型的胃肠道寄生虫负荷更低，这一结果也印证了杂合子优势效应。综上，本研究系统中存在一种免疫遗传权衡机制，影响宿主对寄生虫的抗性与易感性。由于胃肠道寄生虫与体外寄生虫不会在宿主体内直接发生相互作用，我们的研究首次表明，拮抗的寄生虫间相互作用可通过宿主免疫系统实现间接调控。本研究凸显了探究多种寄生虫在塑造宿主免疫遗传变异模式中作用的重要性。