Similarity-Based Analysis of Allele Frequency Distribution among Multiple Populations Identifies Adaptive Genomic Structural Variants

Mol Biol Evol. 2022 Mar 2;39(3):msab313. doi: 10.1093/molbev/msab313.


Structural variants have a considerable impact on human genomic diversity. However, their evolutionary history remains mostly unexplored. Here, we developed a new method to identify potentially adaptive structural variants based on a similarity-based analysis that incorporates genotype frequency data from 26 populations simultaneously. Using this method, we analyzed 57,629 structural variants and identified 576 structural variants that show unusual population differentiation. Of these putatively adaptive structural variants, we further showed that 24 variants are multiallelic and overlap with coding sequences, and 20 variants are significantly associated with GWAS traits. Closer inspection of the haplotypic variation associated with these putatively adaptive and functional structural variants reveals deviations from neutral expectations due to: 1) population differentiation of rapidly evolving multiallelic variants, 2) incomplete sweeps, and 3) recent population-specific negative selection. Overall, our study provides new methodological insights, documents hundreds of putatively adaptive variants, and introduces evolutionary models that may better explain the complex evolution of structural variants.

Keywords: Denisovan; complex traits; copy number variation; neutrality test; population genetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Gene Frequency
  • Genetics, Population*
  • Genomic Structural Variation*
  • Haplotypes
  • Phenotype
  • Selection, Genetic*