Department of Ecology and Evolutionary Biology, University of Connecticut, Storrs, CT, USA.
Department of Ecology and Evolutionary Biology, University of California, Santa Cruz, CA, USA.
Mol Ecol. 2021 Apr;30(7):1659-1671. doi: 10.1111/mec.15840. Epub 2021 Feb 25.
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.
主要组织相容性复合体（MHC）基因编码识别外来蛋白抗原的蛋白质，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多态性最高的基因。进化如何维持这种多样性仍然存在争议。有三个主要假说试图通过病原体介导的选择来解释 MHC 多样性的维持：杂合优势、频率依赖选择和跨越景观或随时间变化的波动选择。在这里，我们使用刺鱼的一个大规模野外寄生虫调查的元种群来检验这些假说中的每一个预测。我们鉴定了超过 1000 种 MHC IIβ 变体（跨越同源基因的等位基因），并发现它们中的许多与寄生虫负荷呈正相关或负相关，这表明这些基因有助于抵抗或易感性。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，即在具有中等数量 MHC 变体的个体中，寄生虫负担最低。我们也没有观察到稀有变异优势或在种群间广泛波动的选择。相比之下，我们发现 MHC 多样性最好由中性全基因组杂合性和种群间基因组分化来预测，这表明中性过程在塑造刺鱼元种群 MHC 多样性模式方面很重要。因此，尽管 MHC IIβ 高度多样化，与这些刺鱼种群中宏观寄生虫感染的类型和强度相关，但 MHC 进化的主要模型在这个系统中仍然提供了很少的解释力。
