Skip to main content
SpringerLink
Log in

Signals of Positive Selection in Human Populations of Siberia and European Russia

  • HUMAN GENETICS
  • Published:
Russian Journal of Genetics Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.

Similar content being viewed by others

REFERENCES

  1. 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

    Article  CAS  PubMed  Google Scholar 

  2. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 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

    Article  PubMed  PubMed Central  Google Scholar 

  4. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 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

    Article  PubMed  Google Scholar 

  7. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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.

    Google Scholar 

  11. 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

    Article  CAS  Google Scholar 

  12. 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

    Article  CAS  Google Scholar 

  13. 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.

    Article  Google Scholar 

  14. 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

    Article  CAS  Google Scholar 

  15. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. 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

  17. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. 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

    Article  Google Scholar 

  20. 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

    Article  CAS  Google Scholar 

  21. 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

    Article  CAS  Google Scholar 

  22. 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

  23. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 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

    Article  CAS  Google Scholar 

  25. 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

    Article  CAS  Google Scholar 

  26. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 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

Download references

Funding

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.”

Author information

Authors and Affiliations

  1. Research Institute of Medical Genetics, Tomsk National Medical Research Center, 634050, Tomsk, Russia

    V. A. Stepanov, V. N. Kharkov, K. V. Vagaitseva, I. Yu. Khitrinskaya, A. V. Bocharova, N. A. Kolesnikov, A. A. Zarubin, A. A. Popovich, A. V. Marusin & M. G. Swarovskaya

  2. Second Faculty of Medicine, Charles University in Prague, 11000, Prague, Czech Republic

    P. Triska

  3. Department of Biology, La Verne University, CA 91750, La Verne, USA

    T. V. Tatarinova

Authors
  1. V. A. Stepanov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. N. Kharkov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. V. Vagaitseva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I. Yu. Khitrinskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. V. Bocharova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. N. A. Kolesnikov
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. A. Zarubin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. A. Popovich
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A. V. Marusin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M. G. Swarovskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. P. Triska
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. T. V. Tatarinova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. A. Stepanov.

Ethics declarations

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.

Additional information

Translated by I. Grishina

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1022795419100120

Keywords:

Search

Navigation