Digging for gold nuggets: uncovering novel candidate genes for variation in gastrointestinal nematode burden in a wild bird species

The extent to which genotypic variation at a priori identified candidate genes can explain variation in complex phenotypes is a major debate in evolutionary biology. Whereas some high-profile genes such as the MHC or MC1R clearly do account for variation in ecologically relevant characters, many complex phenotypes such as response to parasite infection may well be underpinned by a large number of genes, each of small and effectively undetectable effect. Here, we characterize a suite of novel candidate genes for variation in gastrointestinal nematode (Trichostrongylus tenuis) burden among red grouse (Lagopus lagopus scotica) individuals across a network of moors in north-east Scotland. We test for associations between parasite load and genotypic variation in twelve genes previously identified to be differentially expressed in experimentally infected red grouse or genetically differentiated among red grouse populations with overall different parasite loads. These genes are associated with a broad physiological response including immune system processes. Based on individual-level generalized linear models, genotypic variants in nine genes were significantly associated with parasite load, with effect sizes accounting for differences of 514–666 worms per bird. All but one of these variants were synonymous or untranslated, suggesting that these may be linked to protein-coding variants or affect regulatory processes. In contrast, population-level analyses revealed few and inconsistent associations with parasite load, and little evidence of signatures of natural selection. We discuss the broader significance of these contrasting results in the context of the utility of population genomics and landscape genomics approaches in detecting adaptive genomic signatures.

在进化生物学领域，经先验筛选的候选基因的基因型变异能够在多大程度上解释复杂表型的变异，是一个核心争议议题。诸如主要组织相容性复合体（Major Histocompatibility Complex, MHC）与黑皮质素1受体（Melanocortin 1 Receptor, MC1R）这类知名基因，显然确实能够解释与生态相关的性状变异，但诸多复杂表型——例如寄生虫感染应答——很可能由大量效应微弱且实际难以检测的基因共同支撑。
本研究针对苏格兰东北部高沼地采样网络中的红松鸡（*Lagopus lagopus scotica*）个体间的胃肠道线虫（*Trichostrongylus tenuis*）负荷变异，对一系列新型候选基因进行了特征分析。我们针对12个此前已被证实的基因，检测了寄生虫负荷与基因型变异之间的关联：这些基因或在实验感染的红松鸡中呈差异表达，或在寄生虫负荷整体存在差异的红松鸡种群间存在遗传分化。这些基因参与包括免疫应答在内的广泛生理反应。
基于个体水平的广义线性模型（Generalized Linear Model）分析，9个基因的基因型变异与寄生虫负荷存在显著关联，其效应量可导致每只宿主的线虫负荷相差514至666条。这些变异中除1个外，均为同义变异或非翻译区变异，提示它们可能与蛋白质编码变异相关，或对调控过程产生影响。
与之形成对比的是，种群水平的分析仅发现少量且不一致的寄生虫负荷关联，且几乎未检测到自然选择特征的相关证据。
我们结合种群基因组学与景观基因组学方法在检测适应性基因组特征方面的应用价值，探讨了这些对比结果的更广泛意义。