Signals of heterogeneous selection at an MHC locus in geographically proximate ecotypes of sockeye salmon

The genes of the major histocompatibility complex (MHC) are an important component of the vertebrate immune system and can provide insights into the role of pathogen-mediated selection in wild populations. Here we examined variation at the MHC class II peptide binding region in 27 populations of sockeye salmon (Oncorhynchus nerka), distributed among three distinct spawning ecotypes, from a complex of interconnected rivers and lakes in southwestern Alaska. We also obtained genotypes from 90 putatively neutral SNPs for each population to compare the relative roles of demography and selection in shaping the observed MHC variation. We found that MHC divergence was generally partitioned by spawning ecotype (lake beaches, rivers, and streams) and was 30 times greater than variation at neutral markers. Additionally, we observed substantial differences in modes of selection and diversity among ecotypes, with beach populations displaying higher levels of directional selection and lower MHC diversity than the other two ecotypes. Finally, the level of MHC differentiation in our study system was comparable to that observed over much larger geographic ranges, suggesting that MHC variation does not necessarily increase with increasing spatial scale and may instead be driven by fine-scale differences in pathogen communities or pathogen virulence. The low levels of neutral structure and spatial proximity of populations in our study system indicates that MHC differentiation can be maintained through strong selective pressure even when ample opportunities for gene flow exist.

主要组织相容性复合体（major histocompatibility complex，MHC）基因是脊椎动物免疫系统的重要组成部分，可为解析病原体介导的选择在野生种群中的作用提供研究视角。本研究针对阿拉斯加西南部一片互联河湖复合体中的27个红大麻哈鱼（Oncorhynchus nerka）种群，分析了其MHC II类肽结合区的遗传变异，这些种群分属3种截然不同的产卵生态型。我们还为每个种群获取了90个推定中性单核苷酸多态性（SNPs）的基因型，以比较种群统计学与选择在塑造观测到的MHC变异中的相对作用。研究发现，MHC分化整体上呈现出按产卵生态型（湖滩、河流与溪流）聚类的格局，其变异幅度较中性标记高出30倍。此外，我们还观测到不同生态型间的选择模式与多样性存在显著差异：湖滩种群相较于另外两种生态型，表现出更高水平的定向选择与更低的MHC多样性。最后，本研究体系中的MHC分化水平可与更大地理范围内观测到的分化水平相媲美，这表明MHC变异未必随空间尺度扩大而增加，反而可能由病原体群落或病原体毒力的精细尺度差异所驱动。本研究体系中中性遗传结构水平较低且种群空间距离较近，这说明即便存在充足的基因流动机会，强大的选择压力仍可维持MHC分化。