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. Using data on a genome-wide set of single nucleotide polymorphisms (SNPs), we searched for the signals of positive selection in five populations of Siberia and the Russian European North. From 113 to 185 genomic regions with extended homozygous haplotypes blocks containing altogether 771 genes were found in each of the populations. Cross-population search of the selection targets resulted in about 150 genomic regions, 57 of which overlap with the results of haplotype analysis in individual populations. Genomic loci with the most profound signals of positive selection in northern populations include regions of SLC30A9, CACNA1C, KCNQ5, ABCA1, ALDH1A2, CSMD1, RBFOX1, and WWOX, as well as some other genes. Bioinformatics analysis demonstrated that major biological processes where selection targets are implicated are those conferring the response to external stimuli, including proteins, nutrients, and glucose, and defense reactions, including inflammatory immune response. The network of protein-protein interactions of genes under positive selection forms distinct clusters related to a number of biological processes indicated above. Results of the study indicate that non-neutral microevolution mechanisms may play a substantial role in genetic structuring of the human populations during long-term adaptation to unfavorable environmental conditions.
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Sabeti, P.C., Reich, D.E., Higgins, J.M., et al., Detecting recent positive selection in the human genome from haplotype structure, Nature, 2002, vol. 419, no. 6909, pp. 832–837. https://doi.org/10.1038/nature01140
Sabeti, P.C., Varilly, P., Fry, B., et al., Genome-wide detection and characterization of positive selection in human populations, Nature, 2007, vol. 449, no. 7164, pp. 913–918. https://doi.org/10.1038/nature06250
Voight, B.F., Kudaravalli, S., Wen, X., and Pritchard, J.K., A map of recent positive selection in the human genome, PLoS Biol., 2006, vol. 4, no. 3. e72. https://doi.org/10.1371/journal.pbio.0040072
Hancock, A.M., Witonsky, D.B., Gordon, A.S., et al., Adaptations to climate in candidate genes for common metabolic disorders, PLoS Genet., 2008, vol. 4, no. 2. e32. https://doi.org/10.1371/journal.pgen.0040032
Hancock, A.M., Witonsky, D.B., Alkorta-Aranburu, G., et al., Adaptations to climate-mediated selective pressures in humans, PLoS Genet., 2011, vol. 7, no. 4. e1001375. https://doi.org/10.1371/journal.pgen.1001375
Lappalainen, T., Salmela, E., Andersen, P.M., et al., Genomic landscape of positive natural selection in Northern European populations, Eur. J. Hum. Genet., 2010, vol. 18, pp. 471–478. https://doi.org/10.1038/ejhg.2009.184
Rasmussen, M., Li, Y., Lindgreen, S., et al., Ancient human genome sequence of an extinct Palaeo-Eskimo, Nature, 2010, vol. 463, pp. 757–762. https://doi.org/10.1038/nature08835
Grossman, S.R., Andersen, K.G., Shlyakhter, I., et al., Identifying recent adaptations in large-scale genomic data, Cell, 2013, vol. 152, no. 4, pp. 703–713. https://doi.org/10.1016/j.cell.2013.01.035
Cardona, A., Pagani, L., Antao, T., et al., Genome-wide analysis of cold adaptation in indigenous Siberian populations, PLoS One, 2014, vol. 9, no. 5. e98076. https://doi.org/10.1371/journal.pone.0098076
Stepanov, V.A., Candelaria, P., Kho, S., et al., Decanalization of immune response during the dispersion of modern humans: the relationships between genetic diversity in immune system genes and the climatic and geographic factors, Med. Genet., 2013, vol. 12, no. 4, pp. 8–18.
Cherednichenko, A.A., Trifonova, E.A., Vagaitseva, K.V., et al., Association of the genetic polymorphism of cytokines and their receptors with climate and geographic factors in human populations, Russ. J. Genet., 2014, vol. 50, no. 10, pp. 1112—1116. https://doi.org/10.1134/S1022795414100020
Stepanov, V.A., Evolution of genetic diversity and human diseases, Russ. J. Genet., 2016, vol. 52, no. 7, pp. 746—756. https://doi.org/10.1134/S1022795416070103
Stepanov, V.A., Vagajceva, K.V., Bocharova, A.V., and Khar’kov, V.N., Development of multiplex genotyping method of polymorphic markers for genes involved in human adaptation to cold climate, Sci. Evol., 2016, vol. 1, no. 2, pp. 92–101.
Stepanov, V.A., Kharkov, V.N., Vagajceva, K.V., et al., Search for genetic markers of climatic adaptation in populations of North Eurasia, Russ. J. Genet., 2017, vol. 53, no. 11, pp. 1172—1183. https://doi.org/10.1134/S1022795417110114
Triska, P., Chekanov, N., Stepanov, V., et al., Between Lake Baikal and the Baltic Sea: genomic history of the gateway to Europe, BMC Genet., 2017, vol. 18, suppl. 1, p. 110. https://doi.org/10.1186/s12863-017-0578-3
1000 Genomes Project Consortium, Auton, A., Brooks, L.D., et al., A global reference for human genetic variation, Nature, 2015, vol. 526, no. 7571, pp. 68–74. https://doi.org/10.1038/nature15393
Szpiech, Z.A. and Hernandez, R.D., selscan: an efficient multithreaded program to perform EHH-based scans for positive selection, Mol. Biol. Evol., 2014, vol. 31, no. 10, pp. 2824–2827. https://doi.org/10.1093/molbev/msu211
Ferrer-Admetlla, A., Liang, M., Korneliussen, T., and Nielsen, R., On detecting incomplete soft or hard selective sweeps using haplotype structure, Mol. Biol. Evol., 2014, vol. 31, no. 5, pp. 1275–1291. https://doi.org/10.1093/molbev/msu077
Stepanov, V.A., Bocharova, A.V., Marusin, A.V., et al., Replicative association analysis of genetic markers of cognitive traits with Alzheimer’s disease in the Russian population, Mol. Biol. (Moscow), 2014, vol. 44, no. 6, pp. 835–844. https://doi.org/10.7868/S0026898414060160
Stepanov, V.A., Bocharova, A.V., Saduakasova, K.Z., et al., Replicative study of susceptibility to childhoodonset schizophrenia in Kazakhs, Russ. J. Genet., 2015, vol. 51, no. 2, pp. 185–192. https://doi.org/10.1134/S1022795415020143
Bocharova, A.V., Stepanov V.A., Marusin A., Kharkov, V.N., et al., Association study of genetic markers of schizophrenia and its cognitive endophenotypes, Russ. J. Genet., 2017, vol. 53, no. 1, pp. 139–146. https://doi.org/10.1134/S1022795417010033
Stepanov, V.A., Marusin, A., Vagaytseva, K., et al., Genetic variants in CSMD1 gene are associated with cognitive performance in normal elderly population, Genet. Res. Int., 2017, vol. 2017. https://doi.org/10.1155/2017/6293826
Zhang, C., Li, J., Tian, L., et al., Differential natural selection of human zinc transporter genes between African and Non-African populations, Sci. Rep., 2015, vol. 5, p. 9658. https://doi.org/10.1038/srep09658
Huang, D.W., Sherman, B.T., and Lempicki, R.A., Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources, Nat. Protoc., 2009, vol. 4, no. 1, pp. 44–57. https://doi.org/10.1038/nprot.2008.211
Huang, D.W., Sherman, B.T., and Lempicki, R.A., Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists, Nucleic Acids Res., 2009, vol. 37, no. 1, pp. 1–13. https://doi.org/10.1093/nar/gkn923
Snel, B., Lehmann, G., Bork, P., and Huynen, M.A., STRING: a web-server to retrieve and display the repeatedly occurring neighborhood of a gene, Nucleic Acids Res., 2000, vol. 28, no. 18, pp. 3442–3444.
Szklarczyk, D., Morris, J.H., Cook, H., et al., The STRING database in 2017: quality-controlled protein—protein association networks, made broadly accessible, Nucleic Acids Res., 2017, vol. 45. D1. D 362–368. https://doi.org/10.1093/nar/gkw937
This work was supported by the Russian Foundation for Basic Research, grant no. 18-29-13045, entitled “Population Genomics and Human Transcriptome: The Search for Signals of Non-Neutral Evolution.”
Conflict of interests. The authors declare that they have no conflict of interest.
Statement of compliance with standards of research involving humans as subjects. All procedures carried out in a study involving people comply with the ethical standards of the institutional and/or national research ethics committees, the 1964 Helsinki Declaration and its subsequent amendments, or comparable ethics norms. Informed voluntary consent was obtained from each of the participants in the study.
Translated by I. Grishina
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Stepanov, V.A., Kharkov, V.N., Vagaitseva, K.V. et al. Signals of Positive Selection in Human Populations of Siberia and European Russia. Russ J Genet 55, 1250–1258 (2019). https://doi.org/10.1134/S1022795419100120