Data from: Demographic history and adaptation account for clock gene diversity in humans

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 FST 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.

昼夜节律钟（circadian clock）可驱动行为与生理功能产生每日振荡模式，此类振荡往往可预判地球自转所引发的周期性环境变化。在模式生物中，若干调控昼夜节律的基因与纬度之间存在关联。我们针对来自千人基因组计划（1000 Genomes Project）的25个人类昼夜节律钟基因及钟相关基因的116000个单核苷酸多态性（single-nucleotide polymorphism, SNP）位点，以及一组假定为中性多态性的参考数据集，分析了这些位点的等位基因分布情况。昼夜节律钟基因的全球遗传结构与参考数据集的观测结果并无显著差异。随后我们通过两种路径检测局部适应性的证据：一是在岛屿模型与层级模型下搜寻FST（固定分化指数）离群位点，二是采用贝叶斯方法探究等位基因频率与环境变量间的显著关联。根据选取的显著性阈值不同，共有23个基因中的230个SNP位点，或是19个基因中的84个SNP位点，表现出局部适应性特征；而最多有23个基因中的190个SNP位点与一种或多种环境变量存在显著协方差。仅有来自两个基因（NPAS2与AANAT）的两个SNP位点，同时表现出群体分化程度升高，且与至少一种环境变量存在协方差。随后我们验证了经上述分析得到的SNP位点是否属于与不同睡眠时型或睡眠障碍相关的候选SNP集合。其中五个此类SNP位点与环境变量的相关性，佐证了纬度或光周期所具备的选择作用，但该作用显然并非主导性的。