Local adaptation and archaic introgression shape global diversity at human structural variant loci.

Yan, Stephanie M, Sherman, Rachel M, Taylor, Dylan J, Nair, Divya R, Bortvin, Andrew N, Schatz, Michael C, McCoy, Rajiv C (September 2021) Local adaptation and archaic introgression shape global diversity at human structural variant loci. eLife, 10. ISSN 2050-084X

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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.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics Investigative techniques and equipment Investigative techniques and equipment > assays bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > single nucleotide polymorphism > haplotype organism description > animal > mammal > primates > hominids > human bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > insertion/deletion bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > single nucleotide polymorphism Investigative techniques and equipment > assays > whole genome sequencing
CSHL Authors:	Schatz, Michael C.
Communities:	CSHL labs > Schatz lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	16 September 2021
Date Deposited:	21 Oct 2021 20:34
Last Modified:	25 Jan 2024 21:07
PMCID:	PMC8492059
URI:	https://repository.cshl.edu/id/eprint/40395

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