Genome-Wide Analysis of Cold Adaptation in Indigenous Siberian Populations

Following the dispersal out of Africa, where hominins evolved in warm environments for millions of years, our species has colonised different climate zones of the world, including high latitudes and cold environments. The extent to which human habitation in (sub-)Arctic regions has been enabled by cultural buffering, short-term acclimatization and genetic adaptations is not clearly understood. Present day indigenous populations of Siberia show a number of phenotypic features, such as increased basal metabolic rate, low serum lipid levels and increased blood pressure that have been attributed to adaptation to the extreme cold climate. In this study we introduce a dataset of 200 individuals from ten indigenous Siberian populations that were genotyped for 730,525 SNPs across the genome to identify genes and non-coding regions that have undergone unusually rapid allele frequency and long-range haplotype homozygosity change in the recent past. At least three distinct population clusters could be identified among the Siberians, each of which showed a number of unique signals of selection. A region on chromosome 11 (chr11:66–69 Mb) contained the largest amount of clustering of significant signals and also the strongest signals in all the different selection tests performed. We present a list of candidate cold adaption genes that showed significant signals of positive selection with our strongest signals associated with genes involved in energy regulation and metabolism (CPT1A, LRP5, THADA) and vascular smooth muscle contraction (PRKG1). By employing a new method that paints phased chromosome chunks by their ancestry we distinguish local Siberian-specific long-range haplotype signals from those introduced by admixture.在人亚族（hominin）于温暖环境中演化数百万年之后，我们的智人物种走出非洲，并随后拓殖了全球各类气候区域，涵盖高纬度地带与寒冷环境。目前学界尚未明确，人类在（亚）北极地区的定居，究竟在多大程度上依托文化缓冲、短期生理习服与遗传适应性得以实现。现今西伯利亚原住民群体展现出多项表型特征，例如基础代谢率升高、血清脂质水平偏低以及血压偏高，这些特征被认为是对极端寒冷气候的适应性演化结果。在本研究中，我们构建了一套数据集，涵盖西伯利亚10个原住民群体的200名个体，对其全基因组范围内的730525个单核苷酸多态性（Single Nucleotide Polymorphism，SNPs）进行了基因分型，旨在筛选近期经历了非同寻常的等位基因频率快速变化与长范围单倍型纯合性改变的基因与非编码区域。在西伯利亚原住民群体中，至少可区分出三个独立的种群聚类，每个聚类均展现出多项独特的选择信号。11号染色体（chr11:66–69 Mb）上的特定区域，不仅聚集了数量最多的显著选择信号，同时在所有已开展的选择检验中均呈现出最强的选择信号。我们筛选出了一批潜在的寒冷适应候选基因，这些基因均展现出显著的正选择信号，其中最强的信号涉及能量调控与代谢相关基因（CPT1A、LRP5、THADA）以及血管平滑肌收缩相关基因（PRKG1）。我们采用一种全新方法，依据祖先起源对已分相的染色体片段进行标记，借此将西伯利亚本土特异性的长范围单倍型信号与群体混合引入的信号区分开来。