The human serine protease serine 2 TMPRSS2 is involved in the priming of proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a possible target for COVID-19 therapy. The TMPRSS2 gene may be co-expressed with SARS-CoV-2 cell receptor genes angiotensin-converting enzyme 2 (ACE2) and Basigin (BSG), but only TMPRSS2 demonstrates tissue-specific expression in alveolar cells according to single-cell RNA sequencing data. Our analysis of the structural variability of the TMPRSS2 gene based on genome-wide data from 76 human populations demonstrates that a functionally significant missense mutation in exon 6/7 in the TMPRSS2 gene is found in many human populations at relatively high frequencies, with region-specific distribution patterns. The frequency of the missense mutation encoded by rs12329760, which has previously been found to be associated with prostate cancer, ranged between 10% and 63% and was significantly higher in populations of Asian origin compared with European populations. In addition to single-nucleotide polymorphisms, two copy number variants were detected in the TMPRSS2 gene. A number of microRNAs have been predicted to regulate TMPRSS2 and BSG expression levels, but none of them is enriched in lung or respiratory tract cells. Several well-studied drugs can downregulate the expression of TMPRSS2 in human cells, including acetaminophen (paracetamol) and curcumin. Thus, the interactions of TMPRSS2 with SARS-CoV-2, together with its structural variability, gene–gene interactions, expression regulation profiles, and pharmacogenomic properties, characterize this gene as a potential target for COVID-19 therapy.

The genomic data analysis (~886 889 autosomal SNPs) allowed us to estimate the inbreeding level on the basis of the analysis of runs of homozygosity (F_ROH) in a sample of 1836 individuals, including 76 indigenous populations of Siberia, Dagestan, the Caucasus, Volga-Ural region, Eastern Europe, and Central Asia. The data were obtained using the Infinium Multi-Ethnic Global-8 Kit. In the populations of Dagestan, within the Nakh-Daghestanian language family, representatives of several language groups can be distinguished, with the maximum F_ROH level for the Dido group (0.0727) and the Andean group (0.0378), which is similar in values to the populations speaking the Chukchi-Kamchatka and Nivkh languages of Siberia (0.0360). The Siberian populations are characterized by a greater value of the total length of short and medium runs of homozygosity per person. The total length of long ROHs is more variable and much larger in the most of the populations of Dagestan and Siberia compared to other populations of the Caucasus, Central Asia, Europe, and the Volga-Ural region.

The human serine protease TMPRSS2 gene is involved in the priming of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins being one of the possible targets for COVID-19 therapy. TMPRSS2 gene is possibly co-expressed with SARS-CoV-2 cell receptor genes ACE2 and BSG, but only TMPRSS2 demonstrates tissue-specific expression in alveolar cells according to single cell RNA sequencing data. Our analysis of the structural variability of the TMPRSS2 gene based on genome-wide data of 76 human populations demonstrates that functionally significant missense mutation in exon 6/7 in TMPRSS2 gene, was found in many human populations in relatively high frequency, featuring region-specific distribution patterns. The frequency of the missense mutation encoded by the rs12329760, which previously was found to be associated with prostate cancer, is ranged between 10% and 63% being significantly higher in populations of Asian origin compared to European populations. In addition to SNPs, two copy numbers variants (CNV) were detected in the TMPRSS2 gene. Number of microRNAs have been predicted to regulate TMPRSS2 and BSG expression levels, but none of them is enriched in lung or respiratory tract cells. Several well studied drugs can downregulate the expression of TMPRSS2 in human cells, including Acetaminophen (Paracetamol) and Curcumin. Thus TMPRSS2 interaction with the SARS-CoV-2, its structural variability, gene-gene interactions, and expression regulation profiles, and pharmacogenomics properties characterize this gene as a potential target for COVID-19 therapy.

Human adaptation to extreme climatic and geographic conditions mediated by natural selection may be one of the major factors for formation of genetic structure in North Eurasian populations....

The indigenous populations of Siberia are of significant interest for population genomics because of the specificity of their gene pools, which developed in various genetic and demographic conditions. Data on directional selection signals is an important addition to the existing data on the evolution of gene pools and the mechanisms of genetic adaptation of the population of Eurasia. We used genotype array of 1 779 819 SNPs in a group of 477 unrelated subjects, including 20 indigenous populations of Siberia, to search for directional selection signals using a test for extended homozygosity of haplotypes (nSL). The present study detected that all studied populations of Siberia strongly differ from each other in the composition of genes that demonstrate the effect of selection. The largest number of significant signals of natural selection was found in the populations of the Khanty, Koryaks, and Chukchi. The genes ADGRB3, ANO3, CDH13, CUEDC1, and PCDH15 are distinguished among the genomic loci carrying the most pronounced directional selection signals in the northern populations.