Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Patterns of shared signatures of recent positive selection across human populations

Abstract

Signatures of recent positive selection often overlap across human populations, but the question of how often these overlaps represent a single ancestral event remains unresolved. If a single selective event spread across many populations, the same sweeping haplotype should appear in each population and the selective pressure could be common across populations and environments. Identifying such shared selective events could identify genomic loci and human traits important in recent history across the globe. In addition, genomic annotations that recently became available could help attach these signatures to a potential gene and molecular phenotype selected across populations. Here, we present a catalogue of selective sweeps in humans, and identify those that overlap and share a sweeping haplotype. We connect these sweep overlaps with potential biological mechanisms at several loci, including potential new sites of adaptive introgression, the glycophorin locus associated with malarial resistance and the alcohol dehydrogenase cluster associated with alcohol dependency.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Normalizing the iHS by local recombination rate.
Fig. 2: Closely related populations have sweep overlaps more frequently.
Fig. 3: Overlapping sweeps tend to cluster in the genome.
Fig. 4: Enrichment of shared sweeps across population pairs.
Fig. 5: Signatures of positive selection at the GYP locus on chromosome 4.
Fig. 6: Signatures of positive selection at the ADH locus on chromosome 4.

Similar content being viewed by others

References

  1. Tishkoff, S. A. et al. Convergent adaptation of human lactase persistence in Africa and Europe. Nat. Genet. 39, 31–40 (2007).

    Article  CAS  PubMed  Google Scholar 

  2. Kamberov, Y. G. et al. Modeling recent human evolution in mice by expression of a selected EDAR variant. Cell 152, 691–702 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Fumagalli, M. et al. Greenlandic Inuit show genetic signatures of diet and climate adaptation. Science 349, 1343–1347 (2015).

  4. Pickrell, J. K. et al. Signals of recent positive selection in a worldwide sample of human populations. Genome Res. 19, 826–837 (2009).

  5. Coop, G. et al. The role of geography in human adaptation. PLoS Genet. 5, e1000500 (2009).

  6. Metspalu, M. et al. Shared and unique components of human population structure and genome-wide signals of positive selection in South Asia. Am. J. Hum. Genet. 89, 731–744 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Liu, X. et al. Detecting and characterizing genomic signatures of positive selection in global populations. Am. J. Hum. Genet. 92, 866–881 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Aguet, F. et al. Genetic effects on gene expression across human tissues. Nature 550, 204–213 (2017).

    Article  Google Scholar 

  9. Vernot, B. & Akey, J. M. Resurrecting surviving neandertal lineages from modern human genomes. Science 343, 1017–1021 (2014).

    Article  CAS  PubMed  Google Scholar 

  10. Auton, A. et al. A global reference for human genetic variation. Nature 526, 68–74 (2015).

    Article  PubMed  Google Scholar 

  11. Voight, B. F., Kudaravalli, S., Wen, X. & Pritchard, J. K. A map of recent positive selection in the human genome. PLoS Biol. 4, e72 (2006).

  12. Sabeti, P. C. et al. Genome-wide detection and characterization of positive selection in human populations. Nature 449, 913–918 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. McVicker, G., Gordon, D., Davis, C. & Green, P. Widespread genomic signatures of natural selection in hominid evolution. PLoS Genet. 5, e1000471 (2009).

  14. Scheet, P. & Stephens, M. A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase. Am. J. Hum. Genet. 78, 629–644 (2006).

  15. Baum, J., Ward, R. H. & Conway, D. J. Natural selection on the erythrocyte surface. Mol. Biol. Evol. 19, 223–229 (2002).

    Article  CAS  PubMed  Google Scholar 

  16. Wang, H. Y., Tang, H., Shen, C. K. J. & Wu, C. I. Rapidly evolving genes in human. I. The glycophorins and their possible role in evading malaria parasites. Mol. Biol. Evol. 20, 1795–1804 (2003).

    Article  CAS  PubMed  Google Scholar 

  17. Ko, W. Y. et al. Effects of natural selection and gene conversion on the evolution of human glycophorins coding for MNS blood polymorphisms in malaria-endemic African populations. Am. J. Hum. Genet. 88, 741–754 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Leffler, E. M. et al. Resistance to malaria through structural variation of red blood cell invasion receptors. Science 356, eaam6393 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Leffler, E. M. et al. Multiple instances of ancient balancing selection shared between humans and chimpanzees. Science 339, 1578–1582 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Raj, T. et al. Common risk alleles for inflammatory diseases are targets of recent positive selection. Am. J. Hum. Genet. 92, 517–529 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. van der Zanden, L. F. M. et al. Common variants in DGKK are strongly associated with risk of hypospadias. Nat. Genet. 43, 48–50 (2011).

    Article  PubMed  Google Scholar 

  22. Geller, F. et al. Genome-wide association analyses identify variants in developmental genes associated with hypospadias. Nat. Genet. 46, 957–963 (2014).

    Article  CAS  PubMed  Google Scholar 

  23. Paré, G. et al. Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma Homocysteine in a healthy population a genome-wide evaluation of 13 974 participants in the women’s genome health study. Circ. Cardiovasc. Genet 2, 142–150 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  24. van Meurs, J. B. J. et al. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease. Am. J. Clin. Nutr. 98, 668–676 (2013).

  25. Huerta-Sánchez, E. et al. Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA. Nature 512, 194–197 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Racimo, F., Sankararaman, S., Nielsen, R. & Huerta-Sánchez, E. Evidence for archaic adaptive introgression in humans. Nat. Rev. Genet. 16, 359–371 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Racimo, F., Marnetto, D. & Huerta-Sánchez, E. Signatures of archaic adaptive introgression in present-day human populations. Mol. Biol. Evol. 34, 296–317 (2017).

    CAS  PubMed  Google Scholar 

  28. Ding, Q., Hu, Y., Xu, S., Wang, J. & Jin, L. Neanderthal introgression at chromosome 3p21.31 was under positive natural selection in east asians. Mol. Biol. Evol. 31, 683–695 (2014).

    Article  CAS  PubMed  Google Scholar 

  29. Sams, A. J. et al. Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans. Genome Biol. 17, 246 (2016).

  30. Grossman, S. R. et al. Identifying recent adaptations in large-scale genomic data. Cell 152, 703–713 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Enard, D., Messer, P. W. & Petrov, D. A. Genome-wide signals of positive selection in human evolution. Genome Res. 24, 885–895 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yu, F. et al. Population genomic analysis of 962 whole genome sequences of humans reveals natural selection in non-coding regions. PLoS One 10, e0121644 (2015).

  33. Kamburov, A., Wierling, C., Lehrach, H. & Herwig, R. ConsensusPathDB—a database for integrating human functional interaction networks. Nucleic Acids Res. 37, D623–D628 (2009).

    Article  CAS  PubMed  Google Scholar 

  34. Han, Y. et al. Evidence of positive selection on a class I ADH locus. Am. J. Hum. Genet. 80, 441–456 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Edenberg, H. J. The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants. Alcohol Res. Health 30, 5–13 (2007).

    PubMed  PubMed Central  Google Scholar 

  36. Li, D., Zhao, H. & Gelernter, J. Strong association of the alcohol dehydrogenase 1B gene (ADH1B) with alcohol dependence and alcohol-induced medical diseases. Biol. Psychiatry 70, 504–512 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Galinsky, K. J. et al. Fast principal-component analysis reveals convergent evolution of ADH1B in Europe and East Asia. Am. J. Hum. Genet. 98, 456–472 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gelernter, J. et al. Genome-wide association study of alcohol dependence: significant findings in African- and European-Americans including novel risk loci. Mol. Psychiatry 19, 41–49 (2014).

    Article  CAS  PubMed  Google Scholar 

  39. Pashos, E. E. et al. Large, diverse population cohorts of hiPSCs and derived hepatocyte-like cells reveal functional genetic variation at blood lipid-associated loci. Cell Stem Cell 20, 558–570.e10 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lee, S. L., Chau, G. Y., Yao, C. T., Wu, C. W. & Yin, S. J. Functional assessment of human alcohol dehydrogenase family in ethanol metabolism: significance of first-pass metabolism. Alcohol. Clin. Exp. Res. 30, 1132–1142 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Matsuo, K. et al. Alcohol dehydrogenase 2 His47Arg polymorphism influences drinking habit independently of aldehyde dehydrogenase 2 Glu487Lys polymorphism: analysis of 2,299 Japanese subjects. Cancer Epidemiol. Biomark. Prev. 15, 1009–1013 (2006).

    Article  CAS  Google Scholar 

  42. Haller, B. C. & Messer, P. W. SLiM 2: flexible, interactive forward genetic simulations. Mol. Biol. Evol. 34, 230–240 (2017).

    Article  CAS  PubMed  Google Scholar 

  43. Terhorst, J., Kamm, J. A. & Song, Y. S. Robust and scalable inference of population history from hundreds of unphased whole genomes. Nat. Genet. 49, 303–309 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  44. R Development Core Team R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, Vienna, 2016).

  45. Danecek, P. et al. The variant call format and VCFtools. Bioinformatics 27, 2156–2158 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Busing, F. M. T. A., Meijer, E. & Leeden van der, R. Delete-m jackknife for unequal m. Stat. Comput. 9, 3–8 (1999).

    Article  Google Scholar 

  47. Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Vernot, B. et al. Excavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals. Science 352, 235–239 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Simonti, C. N. et al. The phenotypic legacy of admixture between modern humans and Neandertals. Science 351, 737–741 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wang, K., Li, M. & Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank C. Brown and E. Leffler for helpful comments that improved the quality of the manuscript. This work was supported by grants from the National Institutes of Health (NIDDK R01DK101478 to B.F.V., T32GM008216 to K.E.J.) and a fellowship from the Alfred P. Sloan Foundation (BR2012-087 to B.F.V.).

Author information

Authors and Affiliations

Authors

Contributions

K.E.J. and B.F.V. planned the study. K.E.J. assembled input data and performed the experiments. K.E.J. and B.F.V. interpreted the data and wrote the paper.

Corresponding author

Correspondence to Benjamin F. Voight.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Note, Supplementary Figures 1–11.

Life Sciences Reporting Summary

Supplementary Table 1

iHS standardization tables.

Supplementary Tables 2–9

Supplementary Table 2. 1,000 Genomes population information. Supplementary Table 3. Top iHS intervals for 26 populations. Supplementary Table 4. Estimated effective population sizes and sweep interval counts. Supplementary Table 5. Inferred shared sweep intervals. Supplementary Table 6. Observed and null distribution of shared sweep intervals for each population pair. Supplementary Table 7. Intersection of sweep tags with the GWAS catalogue. Supplementary Table 8. Introgressed Neanderthal haplotypes in LD with sweep tag variants. Supplementary Table 9. Association of a sweeping haplotype in YRI with alcohol dependence and alcohol dehydrogenase expression.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Johnson, K.E., Voight, B.F. Patterns of shared signatures of recent positive selection across human populations. Nat Ecol Evol 2, 713–720 (2018). https://doi.org/10.1038/s41559-018-0478-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41559-018-0478-6

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing