Long-read sequencing reveals structural variants are enriched in visible Drosophila phenotypes

Summary

This study investigates the role of genome structural variants (SVs) in classical visible phenotypes of Drosophila melanogaster. Using Oxford Nanopore Technologies long-read sequencing, researchers created highly contiguous de novo genome assemblies for 11 strains and constructed a pangenome graph with nucleotide-resolution SV maps. They analyzed 50 classical phenotypes and uncovered new candidate causal mutations for 15 phenotypes, including tandem duplications, transposable element insertions, and indels. Key findings include linking the wing vein phenotype plexus (px1) to a 1.5 kb partial tandem gene duplication, and the Curved (c1) wing phenotype to a 7.5 kb DM412 retrotransposon disrupting the muscle protein gene Strn-Mlck. The study found that 67.4% of genes causing phenotypic changes harbor candidate SVs >100 bp, compared to an expected 28%, indicating SVs are strongly enriched among large-effect, deleterious visible phenotypes in Drosophila.