Impact of genomic structural variation in Drosophila melanogaster based on population-scale sequencing

Genomic structural variation (SV) is a major determinant for phenotypic variation. Although they have been extensively studied in humans, the nucleotide resolution structure of SVs within the widely-used model organism Drosophila remains unknown. We report a highly accurate, densely validated map of unbalanced SVs comprising 8,962 deletions and 916 tandem duplications in 39 lines derived from short-read DNA sequencing in a natural population (the "Drosophila melanogaster Genetic Reference Panel", DGRP). Most SVs (>90%) were inferred at nucleotide resolution, and a large fraction was genotyped across all samples. Comprehensive analyses of SV formation mechanisms using the short-read data revealed an abundance of SVs formed by mobile element and non-homologous end-joining mediated rearrangements, and clustering of variants into SV hotspots. We further observed a strong depletion of SVs overlapping genes, which, along with population genetics analyses, suggests that these SVs are often deleterious. We inferred several gene fusion events highlighting also the potential role of SVs in the generation of novel protein products. Expression quantitative trait locus (eQTL) mapping revealed the functional impact of our high-resolution SV map, with quantifiable effects at >100 genic loci. We further performed high-coverage (>30×) sequencing in three laboratory strains, one Canton-S and two Oregon-R obtained from different laboratories, to examine their diversity and strain genetic relationships, and to compare their SV set to our DGRP-based SV map