Genomic landscape of the signals of positive natural selection in populations of Northern Eurasia: A view from Northern Russia

Abstract

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.

Unravelling the effect of environment on the genome of Sarda breed ewes using Runs of Homozygosity

“…Also, the LEMD3 gene was reported to be involved in wool traits and highlighted in a selection sweep in a comparison between Australian Merino and Spanish Churra breeds (Gutiérrez‐Gil et al., 2017). Moreover, the NBEA has been found in a selection signature in a worldwide sheep analysis, and it was reported to be under selection in Northern Eurasian human populations adapted to severe climate (Khrunin et al., 2020). Other genes related to the adaptation to the environment are related to vision, RNF24 and the PANK2, that were found to be under selection in Welsh lowland sheep breeds (Sweet‐Jones et al., 2021).…”

The Problem of Vitamin D Scarcity: Cultural and Genetic Solutions by Indigenous Arctic and Tropical Peoples

“…When the genomes of several populations in northern Russia were examined for signals of natural selection, the strongest signal was found at two genes: SLC37A2 and PKNOX2 . The first gene is expressed when vitamin D 3 is present in peripheral blood cells, and the second may have a role in vitamin D metabolism because it lies at the same locus on the opposite strand of DNA [ 36 ].…”

Fine mapping of candidate regions associated with fat deposition in thin and fat tail sheep breeds suggests new insights into molecular aspects of fat tail selection

“…To overcome this problem, we next applied XP-EHH, to detect selected alleles that have risen to near xation in one but not another population, as for this purpose it is more powerful than iHS test. iHS and XP-EHH tests have been combined to search for recent positive selection in humans [24,40,41], and other species such as Plasmodium falciparum [42]. Grossman et al 2010 [43] showed that the F ST and XP-EHH signals peaked more narrowly around the causal variant, making them useful for spatial localization, while iHS is better to distinguish causal variants and contributed little to spatial resolution.…”