1. Evolutionary Biology
  2. Genetics and Genomics
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Local adaptation and archaic introgression shape global diversity at human structural variant loci

Research Article
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Cite this article as: eLife 2021;10:e67615 doi: 10.7554/eLife.67615

Abstract

Large genomic insertions and deletions are a potent source of functional variation, but are challenging to resolve with short-read sequencing, limiting knowledge of the role of such structural variants (SVs) in human evolution. Here, we used a graph-based method to genotype long-read-discovered SVs in short-read data from diverse human genomes. We then applied an admixture-aware method to identify 220 SVs exhibiting extreme patterns of frequency differentiation—a signature of local adaptation. The top two variants traced to the immunoglobulin heavy chain locus, tagging a haplotype that swept to near fixation in certain Southeast Asian populations, but is rare in other global populations. Further investigation revealed evidence that the haplotype traces to gene flow from Neanderthals, corroborating the role of immune-related genes as prominent targets of adaptive introgression. Our study demonstrates how recent technical advances can help resolve signatures of key evolutionary events that remained obscured within technically challenging regions of the genome.

Data availability

All code necessary for reproducing our analysis is available on GitHub (https://github.com/mccoy-lab/sv_selection). SV genotypes, eQTL results, and selection scan results are available on Zenodo (doi: 10.5281/zenodo.4469976).

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Stephanie M Yan

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Rachel M Sherman

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Dylan J Taylor

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5806-4494
  4. Divya R Nair

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Andrew N Bortvin

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Michael C Schatz

    Department of Computer Science, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Rajiv C McCoy

    Department of Biology, Johns Hopkins University, Baltimore, United States
    For correspondence
    rajiv.mccoy@jhu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0615-146X

Funding

National Institutes of Health (R35GM133747)

  • Rajiv C McCoy

National Science Foundation (DBI-1350041)

  • Michael C Schatz

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. George H Perry, Pennsylvania State University, United States

Publication history

  1. Preprint posted: January 26, 2021 (view preprint)
  2. Received: February 18, 2021
  3. Accepted: September 14, 2021
  4. Accepted Manuscript published: September 16, 2021 (version 1)
  5. Version of Record published: October 5, 2021 (version 2)
  6. Version of Record updated: October 7, 2021 (version 3)

Copyright

© 2021, Yan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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