Local adaptation and archaic introgression shape global diversity at human structural variant loci
- Johns Hopkins University, United States
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).
-
1000 Genomes Project phase 3: 30X coverage whole genome sequencingNCBI Bioproject Accession: PRJEB31736.
Article and author information
Author details
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.
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.
Metrics
-
- 4,020
- views
-
- 429
- downloads
-
- 40
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Local adaptation and archaic introgression shape global diversity at human structural variant loci
eLife 10:e67615.
https://doi.org/10.7554/eLife.67615
