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Patterns of shared signatures of recent positive selection across human populations

Nature Ecology & Evolution volume 2, pages 713–720 (2018)Cite this article

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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.

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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.

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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.).

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Authors and Affiliations

  1. Genetics and Gene Regulation Program, Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Kelsey Elizabeth Johnson

  2. Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Benjamin F. Voight

  3. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Benjamin F. Voight

  4. Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Benjamin F. Voight

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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.

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Correspondence to Benjamin F. Voight.

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The authors declare no competing financial interests.

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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.

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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

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