Transposable element profiles reveal cell line identity and loss of heterozygosity in Drosophila cell culture. Issue 2 (15th July 2021)

• Record Type: Journal Article
• Authors: Han, Shunhua; Basting, Preston J; Dias, Guilherme B; Luhur, Arthur; Zelhof, Andrew C; Bergman, Casey M
• Editors: Bateman, J R
• Is Part Of: Genetics. Volume 219:Issue 2(2021)
• Publication Date: 2021-07-15
• Subjects: Drosophila -- transposable element -- cell culture -- cell line authentication -- loss of heterozygosity; Genetics -- Periodicals; 576.5
• DOI: 10.1093/genetics/iyab113
• Languages: English
• ISSNs: 0016-6731

Abstract

Abstract : Proper identification of cell lines is a requirement of rigorous research involving cultured cells. Here we develop an innovative strategy to identify cell lines using transposable element profiles and apply this novel strategy one of the most important model species, Drosophila melanogaster. We clarify the provenance of several Drosophila cell lines and show that loss of heterozygosity affects genome evolution in Drosophila cell culture. Abstract: Cell culture systems allow key insights into biological mechanisms yet suffer from irreproducible outcomes in part because of cross-contamination or mislabeling of cell lines. Cell line misidentification can be mitigated by the use of genotyping protocols, which have been developed for human cell lines but are lacking for many important model species. Here, we leverage the classical observation that transposable elements (TEs) proliferate in cultured Drosophila cells to demonstrate that genome-wide TE insertion profiles can reveal the identity and provenance of Drosophila cell lines. We identify multiple cases where TE profiles clarify the origin of Drosophila cell lines (Sg4, mbn2, and OSS_E) relative to published reports, and also provide evidence that insertions from only a subset of long-terminal repeat retrotransposon families are necessary to mark Drosophila cell line identity. We also develop a new bioinformatics approach to detect TE insertions and estimate intra-sample allele frequencies in legacy whole-genome sequencing data (called ngs_te_mapper2), which revealed loss of heterozygosity as a mechanism shaping the unique TE profiles that identify Drosophila cell lines. Our work contributes to the general understanding of the forces impacting metazoan genomes as they evolve in cell culture and paves the way for high-throughput protocols that use TE insertions to authenticate cell lines in Drosophila and other organisms.