Harbor Branch Oceanographic Institute, Florida Atlantic University, Fort Pierce, FL, United States of America.
PLoS One. 2018 Sep 25;13(9):e0203450. doi: 10.1371/journal.pone.0203450. eCollection 2018.
The vertebrate immune response is mediated through highly adaptive, quickly evolving cell surface receptors, the major histocompatibility complex (MHC). MHC molecules bind and present a diverse array of pathogenic molecules and trigger a cascade of defenses. Use of MHC variation as a marker for population health has also evolved quickly following advances in sequencing methods. We applied a combination of traditional and next generation sequencing methodology to characterize coding (peptide binding region) and regulatory (proximal promoter) sequence variation in MHC Class II DQA and DQB genes between estuarine and coastal populations of the bottlenose dolphin, Tursiops truncatus, an apex predator whose health status is indicative of anthropogenic impacts on the ecosystem. The coding regions had 10 alleles each at DQA and DQB; the promoters had 6 and 7 alleles at DQA and DQB, respectively with variation within key regulatory motifs. Positive selection was observed for the coding regions of both genes while both coding and promoter regions exhibited geographic differences in allele composition that likely indicates diversifying selection across habitats. Most notable was the discovery of a complete duplication of a 14-bp T-box motif in the DQA promoter. Four class II promoter regions (DQA, DQB, DRA, DRB) were characterized in species from four cetacean families (Delphinidae, Monodontidae, Lipotidae, and Physeteridae) and revealed substantial promoter structural diversity across this order. Peptide binding regions may not be the only source of adaptive potential within cetacean MHC for responding to pathogenic threats. These findings are the first analysis of cetacean MHC regulatory motifs, which may divulge unique immunogenetic strategies among cetaceans and reveal how MHC transcriptional control continues to evolve. The combined MHC regulatory and coding data provide new genetic context for distinct vulnerability profiles between coastal and estuarine populations, which are key concerns for health and risk management.
脊椎动物的免疫反应是通过高度适应、快速进化的细胞表面受体——主要组织相容性复合体（MHC）来介导的。MHC 分子结合并呈现出多种多样的病原体分子，并引发一系列防御反应。随着测序方法的进步，利用 MHC 变异作为种群健康的标志物也迅速发展起来。我们应用传统和下一代测序方法的组合，来描述宽吻海豚（Tursiops truncatus）的河口和沿海种群中 MHC II 类 DQA 和 DQB 基因的编码（肽结合区）和调控（近端启动子）序列变异，宽吻海豚是一种顶级掠食者，其健康状况表明了对生态系统的人为影响。DQA 和 DQB 的编码区各有 10 个等位基因；DQA 和 DQB 的启动子分别有 6 个和 7 个等位基因，关键调控基序内存在变异。两个基因的编码区都观察到正选择，而编码区和启动子区都表现出等位基因组成的地理差异，这可能表明在不同生境中存在多样化选择。最值得注意的是，在 DQA 启动子中发现了一个完整的 14 个碱基对 T 盒基序的重复。在四个鲸类家族（海豚科、喙鲸科、一角鲸科和抹香鲸科）的物种中，对四个 II 类基因的启动子区域（DQA、DQB、DRA 和 DRB）进行了特征描述，揭示了这个目内的大量启动子结构多样性。肽结合区可能不是鲸类 MHC 适应潜在性的唯一来源，用于应对致病威胁。这些发现是对鲸类 MHC 调控基序的首次分析，这可能揭示了鲸类之间独特的免疫遗传策略，并揭示了 MHC 转录控制如何继续进化。结合的 MHC 调控和编码数据为沿海和河口种群之间的不同脆弱性特征提供了新的遗传背景，这是健康和风险管理的关键关注点。
