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.
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).
Data from: Local adaptation and archaic introgression shape global diversity at human structural variant lociZenodo, doi: 10.5281/zenodo.4469976.
1000 Genomes Project phase 3: 30X coverage whole genome sequencingNCBI Bioproject Accession: PRJEB31736.
RNA-sequencing of 465 lymphoblastoid cell lines from the 1000 GenomesEBI ArrayExpress: E-GEUV-1.
- Rajiv C McCoy
- Michael C Schatz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- George H Perry, Pennsylvania State University, United States
© 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.