The underlying neurological events accompanying dog domestication remain elusive. To reconstruct the domestication process in an experimental setting, silver foxes (Vulpes vulpes) have been deliberately bred for tame vs aggressive behaviors for more than 50 generations at the Institute for Cytology and Genetics in Novosibirsk, Russia. The hypothalamus is an essential part of the hypothalamic-pituitary-adrenal axis and regulates the fight-or-flight response, and thus, we hypothesized that selective breeding for tameness/aggressiveness has shaped the hypothalamic transcriptomic profile. RNA-seq analysis identified 70 differentially expressed genes (DEGs). Seven of these genes, DKKL1, FBLN7, NPL, PRIMPOL, PTGRN, SHCBP1L and SKIV2L, showed the same direction expression differences in the hypothalamus, basal forebrain and prefrontal cortex. The genes differentially expressed across the three tissues are involved in cell division, differentiation, adhesion and carbohydrate processing, suggesting an association of these processes with selective breeding. Additionally, 159 transcripts from the hypothalamus demonstrated differences in the abundance of alternative spliced forms between the tame and aggressive foxes. Weighted gene coexpression network analyses also suggested that gene modules in hypothalamus were significantly associated with tame vs aggressive behavior. Pathways associated with these modules include signal transduction, interleukin signaling, cytokine-cytokine receptor interaction and peptide ligand-binding receptors (eg, G-protein coupled receptor [GPCR] ligand binding). Current studies show the selection for tameness vs aggressiveness in foxes is associated with unique hypothalamic gene profiles partly shared with other brain regions and highlight DEGs involved in biological processes such as development, differentiation and immunological responses. The role of these processes in fox and dog domestication remains to be determined.

中文翻译：

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下丘脑转录组的驯服和攻击性银狐（狐狸狐狸）识别基因表达差异在大脑区域之间共享。

伴随犬驯化的潜在神经系统事件仍然难以捉摸。为了在实验环境中重建驯化过程，银狐（Vulpes vulpes）在俄罗斯新西伯利亚的细胞学和遗传研究所被故意培育了50多个世代，以进行驯服和攻击行为。下丘脑是下丘脑-垂体-肾上腺轴的重要组成部分，并调节战斗或逃跑反应，因此，我们假设驯化/攻击性的选择性繁殖已塑造了下丘脑的转录组。RNA-seq分析鉴定出70个差异表达基因（DEG）。这些基因中的七个，DKKL1，FBLN7，NPL，PRIMPOL，PTGRN，SHCBP1L和SKIV2L，在下丘脑，基底前脑和前额叶皮层中显示相同的方向表达差异。在三个组织中差异表达的基因参与细胞分裂，分化，粘附和碳水化合物加工，表明这些过程与选择性育种相关。此外，下丘脑的159个转录本显示出驯服性狐狸和攻击性狐狸在其他剪接形式上的差异。加权基因共表达网络分析还表明，下丘脑中的基因模块与驯服与攻击行为显着相关。与这些模块相关的途径包括信号转导，白介素信号传导，细胞因子-细胞因子受体相互作用和肽配体结合受体（例如，G蛋白偶联受体[GPCR]配体结合）。目前的研究表明，对狐狸驯服与攻击性的选择与部分与其他大脑区域共享的下丘脑基因特征有关，并突显了参与生物过程（如发育，分化和免疫反应）的DEG。这些过程在狐狸和狗驯养中的作用尚待确定。