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Demographic history and adaptation account for clock gene diversity in humans

机译:人口历史和适应因素说明了人类时钟基因的多样性

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Circadian clocks give rise to daily oscillations in behavior and physiological functions that often anticipate upcoming environmental changes generated by the Earth rotation. In model organisms a relationship exists between several genes affecting the circadian rhythms and latitude. We investigated the allele distributions at 116 000 single-nucleotide polymorphisms (SNPs) of 25 human clock and clock-related genes from the 1000Genomes Project, and at a reference data set of putatively neutral polymorphisms. The global genetic structure at the clock genes did not differ from that observed at the reference data set. We then tested for evidence of local adaptation searching for F-ST outliers under both an island and a hierarchical model, and for significant association between allele frequencies and environmental variables by a Bayesian approach. A total of 230 SNPs in 23 genes, or 84 SNPs in 19 genes, depending on the significance thresholds chosen, showed signs of local adaptation, whereas a maximum of 190 SNPs in 23 genes had significant covariance with one or more environmental variables. Only two SNPs from two genes (NPAS2 and AANAT) exhibit both elevated population differentiation and covariance with at least one environmental variable. We then checked whether the SNPs emerging from these analyses fall within a set of candidate SNPs associated with different chronotypes or sleep disorders. Correlation of five such SNPs with environmental variables supports a selective role of latitude or photoperiod, but certainly not a major one.
机译:昼夜节律时钟会引起行为和生理功能的日常振荡,这些振荡通常会预料到地球自转会导致即将发生的环境变化。在模型生物中,影响昼夜节律和纬度的几个基因之间存在关系。我们调查了1000个基因组计划中25个人类时钟和与时钟相关的基因在116 000个单核苷酸多态性(SNP)处的等位基因分布,以及推定的中性多态性的参考数据集。时钟基因处的全局遗传结构与参考数据集上观察到的无异。然后,我们测试了是否有局部适应性证据在岛和分层模型下搜索F-ST异常值,并通过贝叶斯方法对等位基因频率与环境变量之间的显着关联进行了测试。 23个基因中共有230个SNP,或者19个基因中有84个SNP,这取决于选择的显着性阈值,显示出局部适应的迹象,而23个基因中最多190个SNP具有一个或多个环境变量的显着协方差。来自两个基因(NPAS2和AANAT)的仅两个SNP表现出较高的群体分化和具有至少一个环境变量的协方差。然后,我们检查了从这些分析中得出的SNP是否属于与不同的表型或睡眠障碍相关的一组候选SNP。五个这样的SNP与环境变量的相关性支持纬度或光周期的选择性作用,但肯定不是主要的作用。

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