Major Histocompatibility Complex (MHC) genes code for proteins that recognize foreign protein antigens to initiate T‐cell‐mediated adaptive immune responses. They are often the most polymorphic genes in vertebrate genomes. How evolution maintains this diversity remains of debate. Three main hypotheses seek to explain the maintenance of MHC diversity by invoking pathogen‐mediated selection: heterozygote advantage, frequency‐dependent selection, and fluctuating selection across landscapes or through time. Here, we use a large‐scale field parasite survey in a stickleback metapopulation to test predictions derived from each of these hypotheses. We identify over 1000 MHC IIβ variants (alleles spanning paralogous genes) and find that many of them covary positively or negatively with parasite load, suggesting that these genes contribute to resistance or susceptibility. However, despite our large sample‐size, we find no evidence for the widely cited stabilizing selection on MHC heterozygosity, in which individuals with an intermediate number of MHC variants have the lowest parasite burden. Nor do we observe a rare‐variant advantage, or widespread fluctuating selection across populations. In contrast, we find that MHC diversity is best predicted by neutral genome‐wide heterozygosity and between‐population genomic divergence, suggesting neutral processes are important in shaping the pattern of metapopulation MHC diversity. Thus, although MHC IIβ is highly diverse and relevant to the type and intensity of macroparasite infection in these populations of stickleback, the main models of MHC evolution still provide little explanatory power in this system.

中文翻译：

---

哪些进化过程维持了刺鱼种群内部和种群之间的 MHC IIꞵ 多样性？


主要组织相容性复合体 (MHC) 基因编码的蛋白质可识别外来蛋白质抗原，从而启动 T 细胞介导的适应性免疫反应。它们通常是脊椎动物基因组中最多态性的基因。进化如何维持这种多样性仍然存在争议。三个主要假设试图通过病原体介导的选择来解释 MHC 多样性的维持：杂合子优势、频率依赖性选择以及跨景观或时间的波动选择。在这里，我们对刺鱼集合种群进行了大规模的现场寄生虫调查，以测试从每个假设得出的预测。我们鉴定了超过 1000 个 MHC IIβ 变体（跨越旁系同源基因的等位基因），并发现其中许多与寄生虫负载呈正向或负向共变，这表明这些基因有助于抵抗或易感。然而，尽管我们的样本量很大，但我们没有发现广泛引用的 MHC 杂合性稳定选择的证据，其中具有中等数量 MHC 变异的个体具有最低的寄生虫负担。我们也没有观察到稀有变异的优势，或者人群中广泛的波动选择。相比之下，我们发现 MHC 多样性最好是通过中性全基因组杂合性和群体间基因组差异来预测，这表明中性过程对于塑造亚群体 MHC 多样性模式很重要。因此，尽管 MHC IIβ 具有高度多样性，并且与这些刺鱼种群中大型寄生虫感染的类型和强度相关，但 MHC 进化的主要模型仍然对该系统提供很少的解释力。