Department of Molecular Bases of Human Genetics, Institute of Molecular Genetics of Russian Academy of Sciences, Moscow, Russia.
Department of Medicine, University of Toledo, Toledo, Ohio, United States of America.
PLoS One. 2020 Feb 5;15(2):e0228778. doi: 10.1371/journal.pone.0228778. eCollection 2020.
Natural selection of beneficial genetic variants played a critical role in human adaptation to a wide range of environmental conditions. Northern Eurasia, despite its severe climate, is home to lots of ethnically diverse populations. The genetic variants associated with the survival of these populations have hardly been analyzed. We searched for the genomic signatures of positive selection in (1) the genome-wide microarray data of 432 people from eight different northern Russian populations and (2) the whole-genome sequences of 250 people from Northern Eurasia from a public repository through testing the extended haplotype homozigosity (EHH) and direct comparison of allele frequency, respectively. The 20 loci with the strongest selection signals were characterized in detail. Among the top EHH hits were the NRG3 and NBEA genes, which are involved in the development and functioning of the neural system, the PTPRM gene, which mediates cell-cell interactions and adhesion, and a region on chromosome 4 (chr4:28.7-28.9 Mb) that contained several loci affiliated with different classes of non-coding RNAs (RN7SL101P, MIR4275, MESTP3, and LINC02364). NBEA and the region on chromosome 4 were novel selection targets that were identified for the first time in Western Siberian populations. Cross-population comparisons of EHH profiles suggested a particular role for the chr4:28.7-28.9 Mb region in the local adaptation of Western Siberians. The strongest selection signal identified in Siberian sequenced genomes was formed by six SNPs on chromosome 11 (chr11:124.9-125.2 Mb). This region included well-known genes SLC37A2 and PKNOX2. SLC37A2 is most-highly expressed in the gut. Its expression is regulated by vitamin D, which is often deficient in northern regions. The PKNOX2 gene is a transcription factor of the homeobox family that is expressed in the brain and many other tissues. This gene is associated with alcohol addiction, which is widespread in many Northern Eurasian populations.
自然选择有益的遗传变异在人类适应广泛的环境条件中发挥了关键作用。尽管北亚的气候恶劣，但它却是许多种族多样化的人口的家园。与这些人口的生存相关的遗传变异几乎没有被分析过。我们通过扩展的单倍型同质性（EHH）测试和等位基因频率的直接比较，分别在（1）来自八个不同俄罗斯北部人群的 432 人的全基因组微阵列数据和（2）来自公共存储库的北亚的 250 人的全基因组序列中，搜索了与正选择相关的基因组特征。详细描述了 20 个具有最强选择信号的基因座。在 EHH 命中的前 20 个基因中，包括参与神经系统发育和功能的 NRG3 和 NBEA 基因、介导细胞间相互作用和黏附的 PTPRM 基因，以及染色体 4 上的一个区域（chr4:28.7-28.9 Mb），该区域包含多个与不同非编码 RNA（RN7SL101P、MIR4275、MESTP3 和 LINC02364）类别相关的基因座。NBEA 和染色体 4 上的区域是首次在西西伯利亚人群中确定的新的选择靶点。EHH 谱的跨人群比较表明，chr4:28.7-28.9 Mb 区域在西西伯利亚人的局部适应中具有特殊作用。在西伯利亚测序基因组中确定的最强选择信号是由染色体 11 上的六个 SNPs（chr11:124.9-125.2 Mb）形成的。该区域包括著名的 SLC37A2 和 PKNOX2 基因。SLC37A2 在肠道中表达最高。其表达受维生素 D 调节，而维生素 D 在北方地区通常缺乏。PKNOX2 基因是一种同源盒家族的转录因子，在大脑和许多其他组织中表达。该基因与许多北亚人群中广泛存在的酒精成瘾有关。
