University of Missouri, 401 Tucker Hall, Columbia, MO, 65211, USA.
BMC Genomics. 2020 Jan 28;21(1):84. doi: 10.1186/s12864-020-6467-6.
Environmental variation in the amount of resources available to populations challenge individuals to optimize the allocation of those resources to key fitness functions. This coordination of resource allocation relative to resource availability is commonly attributed to key nutrient sensing gene pathways in laboratory model organisms, chiefly the insulin/TOR signaling pathway. However, the genetic basis of diet-induced variation in gene expression is less clear.
To describe the natural genetic variation underlying nutrient-dependent differences, we used an outbred panel derived from a multiparental population, the Drosophila Synthetic Population Resource. We analyzed RNA sequence data from multiple female tissue samples dissected from flies reared in three nutritional conditions: high sugar (HS), dietary restriction (DR), and control (C) diets. A large proportion of genes in the experiment (19.6% or 2471 genes) were significantly differentially expressed for the effect of diet, and 7.8% (978 genes) for the effect of the interaction between diet and tissue type (LRT, P < 0.05). Interestingly, we observed similar patterns of gene expression relative to the C diet, in the DR and HS treated flies, a response likely reflecting diet component ratios. Hierarchical clustering identified 21 robust gene modules showing intra-modularly similar patterns of expression across diets, all of which were highly significant for diet or diet-tissue interaction effects (FDR P < 0.05). Gene set enrichment analysis for different diet-tissue combinations revealed a diverse set of pathways and gene ontology (GO) terms (two-sample t-test, FDR < 0.05). GO analysis on individual co-expressed modules likewise showed a large number of terms encompassing many cellular and nuclear processes (Fisher exact test, P < 0.01). Although a handful of genes in the IIS/TOR pathway including Ilp5, Rheb, and Sirt2 showed significant elevation in expression, many key genes such as InR, chico, most insulin peptide genes, and the nutrient-sensing pathways were not observed.
Our results suggest that a more diverse network of pathways and gene networks mediate the diet response in our population. These results have important implications for future studies focusing on diet responses in natural populations.
种群可利用资源数量的环境变化促使个体优化资源分配以适应关键的适应度功能。这种资源分配与资源可用性的协调通常归因于实验室模式生物中关键营养感应基因途径，主要是胰岛素/TOR 信号通路。然而，饮食诱导的基因表达变化的遗传基础尚不清楚。
为了描述营养依赖差异的基础上的自然遗传变异，我们使用了源自多亲本群体的杂交群体，即果蝇合成种群资源。我们分析了从在三种营养条件下培养的雌性组织样本中分离出的 RNA 序列数据：高糖 (HS)、饮食限制 (DR) 和对照 (C) 饮食。实验中的很大一部分基因（19.6%或 2471 个基因）因饮食的影响而显著差异表达，7.8%（978 个基因）因饮食与组织类型之间的相互作用的影响而差异表达（LRT，P<0.05）。有趣的是，我们观察到在 DR 和 HS 处理的果蝇中，相对于 C 饮食的基因表达模式相似，这种反应可能反映了饮食成分的比例。层次聚类确定了 21 个稳健的基因模块，这些模块在不同饮食之间表现出模块内相似的表达模式，所有这些模块在饮食或饮食-组织相互作用的影响方面均具有高度显著性（FDR P<0.05）。不同饮食-组织组合的基因集富集分析揭示了一组多样化的途径和基因本体 (GO) 术语（双样本 t 检验，FDR<0.05）。对单个共表达模块的 GO 分析同样显示了许多包含许多细胞和核过程的术语（Fisher 精确检验，P<0.01）。尽管 IIS/TOR 途径中的少数基因，如 Ilp5、Rheb 和 Sirt2，表现出显著的上调表达，但许多关键基因，如 InR、chico、大多数胰岛素肽基因和营养感应途径，并没有观察到。
我们的结果表明，更广泛的途径和基因网络网络介导了我们群体中的饮食反应。这些结果对未来专注于自然种群饮食反应的研究具有重要意义。
