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

Area of Science:

• Genomics
• Human Evolution
• Population Genetics

Background:

• Large genomic insertions and deletions (structural variants or SVs) are key sources of functional variation.
• Short-read sequencing technologies present challenges in resolving these SVs, limiting our understanding of their role in human evolution.

Purpose of the Study:

• To develop and apply a graph-based method for genotyping SVs discovered by long-read sequencing using short-read data.
• To identify SVs under local adaptation in diverse human populations.

Main Methods:

• Genotyping of long-read-discovered SVs in short-read data from diverse human genomes using a graph-based approach.
• Application of an admixture-aware method to detect SVs with extreme frequency differentiation, indicative of local adaptation.

Main Results:

• Identified 220 SVs showing patterns of local adaptation.
• Discovered two top variants at the immunoglobulin heavy chain locus, associated with a haplotype near fixation in Southeast Asian populations.
• Found evidence that this adaptive haplotype originated from Neanderthal gene flow, highlighting immune genes as targets of adaptive introgression.

Conclusions:

• Recent technical advances enable the resolution of SVs and the study of their evolutionary impact.
• Immune-related genes were likely targets of adaptive introgression from Neanderthals.
• The study resolves previously obscured signatures of key evolutionary events in challenging genomic regions.