The biological basis of exercise behavior is increasingly relevant for maintaining healthy lifestyles. Various quantitative genetic studies and selection experiments have conclusively demonstrated substantial heritability for exercise behavior in both humans and laboratory rodents. In the "High Runner" selection experiment, 4 replicate lines of Mus domesticus were bred for high voluntary wheel running (HR), along with 4 non-selected control (C) lines. After 61 generations, the genomes of 79 mice (9-10 from each line) were fully sequenced and single nucleotide polymorphisms (SNPs) were identified. We used nested ANOVA with MIVQUE estimation and other approaches to compare allele frequencies between the HR and C lines for both SNPs and haplotypes. Approximately 61 genomic regions, across all somatic chromosomes, showed evidence of differentiation. Twelve of these regions were differentiated by all methods of analysis. Gene function was inferred largely using Panther gene ontology terms and KO phenotypes associated with genes of interest. Some of the differentiated genes are known to be associated with behavior/motivational systems and/or athletic ability, including Sorl1, Dach1, and Cdh10 Sorl1 is a sorting protein associated with cholinergic neuron morphology, vascular wound healing, and metabolism. Dach1 is associated with limb bud development and neural differentiation. Cdh10 is a calcium ion binding protein associated with phrenic neurons. Overall, these results indicate that selective breeding for high voluntary exercise has resulted in changes in allele frequencies for multiple genes associated with both motivation and ability for endurance exercise, providing candidate genes that may explain phenotypic changes observed in previous studies.

中文翻译：

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有氧支持的自愿运动的遗传基础：家鼠选择实验的结果。

运动行为的生物学基础与维持健康的生活方式越来越相关。各种定量遗传学研究和选择实验已最终证明人类和实验室啮齿动物的运动行为具有显着的遗传性。在“High Runner”选择实验中，培育了4 个家鼠复制品系用于高自愿轮跑（HR），以及 4 个未选择的对照（C）品系。61 代后，79 只小鼠（每系 9-10 只）的基因组被完全测序，并鉴定出单核苷酸多态性 (SNP)。我们使用嵌套方差分析与 MIVQUE 估计和其他方法来比较 HR 和 C 系之间 SNP 和单倍型的等位基因频率。所有体细胞染色体上大约 61 个基因组区域显示出分化的证据。通过所有分析方法区分了其中十二个区域。基因功能主要使用 Panther 基因本体论术语和与感兴趣基因相关的 KO 表型来推断。已知一些分化基因与行为/动机系统和/或运动能力相关，包括Sorl1、Dach1和Cdh10。 Sorl1 是一种与胆碱能神经元形态、血管伤口愈合和新陈代谢相关的分选蛋白。Dach1与肢芽发育和神经分化相关。Cdh10是一种与膈神经元相关的钙离子结合蛋白。总体而言，这些结果表明，高自愿运动的选择性育种导致了与耐力运动的动机和能力相关的多个基因的等位基因频率的变化，提供了可能解释先前研究中观察到的表型变化的候选基因。